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Medicine › Hematology

Hematopoietic Stem Cell Transplantation

Works Count: 65442

Description

This cluster of papers focuses on the biology, regulation, and clinical applications of hematopoietic stem cells (HSCs) within the bone marrow niche. It covers topics such as HSC quiescence, stem cell aging, graft-versus-host disease, hematologic malignancies, and the role of mesenchymal stem cells in supporting HSC function. Additionally, it explores the mechanisms of stem cell mobilization and transplantation for therapeutic purposes.

Keywords

Hematopoietic Stem Cells; Bone Marrow Niche; Graft-versus-Host Disease; Stem Cell Quiescence; Hematopoietic Cell Transplantation; Stem Cell Aging; Hematopoietic Progenitor Cells; Stem Cell Mobilization; Mesenchymal Stem Cells; Hematologic Malignancies

AC133, a Novel Marker for Human Hematopoietic Stem and Progenitor Cells

1997-12-15
Amy H. Yin , Sheri Miraglia , Esmail D. Zanjani +6 more
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Graft-versus-leukemia reactions after bone marrow transplantation

1990-02-01
MM Horowitz , Gale Rp , Sondel Pm +7 more
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Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia [see comments]

1995-09-01
HJ Kolb , A Schattenberg , JM Goldman +7 more
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Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues.

1968-03-01
A. J. Friedenstein , K. V. Petrakova , Alexandra Ivanovna Kurolesova +1 more
In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the … In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the initial donor line. In syngeneic and semisyngeneic grafts of bone marrow under the renal capsule bone and bone marrow are formed. In allogeneic grafts only bone is formed; this bone is subsequently resorbed. In 14-month semisyngeneic transplants the bone marrow consists of recipient cells. This is true for both the proliferating pool and the stem cells of hematopoietic tissue. At the same time, osteogenic precursor cells and bone tissue in these transplants are of donor origin. A discussion is presented of the interrelationship between determinated osteogenic precursor cells (preosteoblasts) and hematopoietic stem cells (or their descendants) in which osteogenesis is inducible.

Differentiation and proliferation of hematopoietic stem cells

1993-06-01
Megumu Ogawa

Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.

1997-02-01
Robert H. Collins , Ofer Shpilberg , William R. Drobyski +7 more
PURPOSE Recipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed … PURPOSE Recipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed a retrospective study to characterize better this new treatment modality. PATIENTS AND METHODS We surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Detailed forms were used to gather data regarding the original BMT, relapse, DLI, response to DLI, complications of DLI, and long-term follow-up evaluation. Reports of 140 patients were thus available for analysis. RESULTS Complete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-phase (16.7%; 95% CI, 1.9% to 31.9%) relapse. The actuarial probability of remaining in complete remission at 2 years was 89.6%. Complete remission rates in acute myelogenous leukemia (AML) (n = 39) and acute lymphocytic leukemia (ALL) (n = 11) patients who had not received pre-DLI chemotherapy were 15.4% (95% CI, 9.6% to 21.2%) and 18.2% (95% CI, 6.6% to 29.8%), respectively. Complete remissions were also observed in two of four assessable myeloma patients and two of five assessable myelodysplasia patients. Complications of DLI included acute graft-versus-host disease (GVHD) (60%; 95% CI, 51.4% to 68.6%), chronic GVHD (60.7%; 95% CI, 50.3% to 71.1%), and pancytopenia (18.6%; 95% CI, 12.2% to 25.0%). Pre-DLI characteristics predictive of complete response in CML patients were post-BMT chronic GVHD, pre-DLI disease status of chronic phase, and time interval between BMT to DLI less than 2 years. Acute and chronic GVHD post-DLI were highly correlated with disease response (P < .00001). CONCLUSION DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

Antileukemic Effect of Graft-versus-Host Disease in Human Recipients of Allogeneic-Marrow Grafts

1979-05-10
P L Weiden , Nancy Flournoy , E D Thomas +4 more
To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, … To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, 117 recipients of HLA-identical-sibling (allogeneic) marrow with no or minimal graft-versus-host disease, and 79 recipients of allogeneic marrow with moderate to severe or chronic disease. The relative relapse rate was 2.5 times less in allogeneic-marrow recipients with graft-versus-host disease than in recipients without it (P less than 0.01). This apparent antileukemic effect was more marked in patients with lymphoblastic than nonlymphoblastic leukemia, and in those who received transplants during relapse rather than during remission, and was most evident during the first 130 days after transplantation. Survival of all patients was comparable since the lesser probability of recurrent leukemia in patients with graft-versus-host disease was offset by a greater probability of other causes of death.

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

2010-08-01
Simón Méndez‐Ferrer , Tatyana V. Michurina , Francesca Ferraro +7 more
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Purification and Characterization of Mouse Hematopoietic Stem Cells

1988-07-01
Gerald J. Spangrude , Shelly Heimfeld , Irving L. Weissman
Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers. These cells can proliferate and differentiate with approximately unit efficiency into myelomonocytic cells, … Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers. These cells can proliferate and differentiate with approximately unit efficiency into myelomonocytic cells, B cells, or T cells. Thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors.

Identification of the haematopoietic stem cell niche and control of the niche size

2003-10-01
Jiwang Zhang , Chao Niu , Ling Ye +7 more
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Human bone marrow colony growth in agar‐gel

1970-08-01
Beverley L. Pike , William A. Robinson
Abstract A technique for growing human bone marrow cell colonies in agar‐gel medium is described. “Feeder layers” containing 1 × 10 6 normal human peripheral white blood cells are used … Abstract A technique for growing human bone marrow cell colonies in agar‐gel medium is described. “Feeder layers” containing 1 × 10 6 normal human peripheral white blood cells are used as the stimulus for colony growth. Human bone marrow aspirates are collected in heparinized syringes and plated as 2 × 10 5 cells on “feeder layers.” Normal human bone marrow yields 32–102 colonies per 2 × 10 5 cells plated. Colonies are almost exclusively granulocytic. Growth rate of colonies is slower than with mouse bone marrow but colonies reach a comparable size (500–1500 cells) at days 12–16.

Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells

2006-03-26
Keisuke Ito , Atsushi Hirao , Fumio Arai +7 more

Reduced Mortality after Allogeneic Hematopoietic-Cell Transplantation

2010-11-24
Ted Gooley , Jason W. Chien , Steven A. Pergam +7 more
Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation.We … Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation.We analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation.In the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs.We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).
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Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell

2001-05-01
Diane S. Krause , Neil D. Theise , Michael I. Collector +5 more
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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells

2003-04-20
In-Kyung Park , Dalong Qian , Mark J. Kiel +5 more
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CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation

2003-08-17
Matthias Edinger , Petra Hoffmann , Joerg Ermann +4 more

HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

2008-05-18
Leo Luznik , Paul V. O’Donnell , Heather J. Symons +7 more
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Bone-marrow haematopoietic-stem-cell niches

2006-02-01
Anne Wilson , Andreas Trumpp

Endothelial and perivascular cells maintain haematopoietic stem cells

2012-01-01
Lei Ding , Thomas L. Saunders , Grigori Enikolopov +1 more
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Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells

2002-09-27
Amy J. Wagers , Richard I. Sherwood , Julie L. Christensen +1 more
To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked … To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.
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Graft-versus-host disease

2009-03-13
James L.M. Ferrara , John E. Levine , Pavan Reddy +1 more
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CLINICAL MANIFESTATIONS OF GRAFT-VERSUS-HOST DISEASE IN HUMAN RECIPIENTS OF MARROW FROM HL-A-MATCHED SIBLING DONOR,S

1974-10-01
Harold Glucksberg , Rainer Storb , A Fefer +5 more
Sixty-one evaluable patients, 19 with advanced aplastic anemia and 42 with end stage hematological malignancies, were conditioned for marrow grafting with total body irradiation or cyclophosphamide, or a combination of … Sixty-one evaluable patients, 19 with advanced aplastic anemia and 42 with end stage hematological malignancies, were conditioned for marrow grafting with total body irradiation or cyclophosphamide, or a combination of both. Marrow graft donors were siblings matched at the HL-A region and nonreactive in mixed leukocyte culture. All patients received methotrexate postgrafting to modify anticipated graft-versus-host disease (GVHD). Forty-three of the 61 patients developed clinically recognizable GVHD. In seven GVHD was limited to the skin. In the remaining patients, skin involvement was more severe and was followed by gastrointestinal involvement manifested by anorexia, nausea, diarrhea, abdominal pain, and malabsorption and/or liver involvement manifested by hepatomegaly, rises in serum glutamic oxaloacetic acid transaminase, and bilirubin. The severity of GVHD showed no correlation with the underlying disease, the conditioning regimen, or the day of onset after grafting. Fourteen of 25 patients without GVHD or with only skin involvement are alive. By contrast, only 5 of 36 with severe GVHD are alive. Twenty-six of the 36 patients with severe GVHD succumbed to infection, whereas only 4 of 25 without GVHD or with only skin involvement did so. The results show that despite histocompatibility matching and methotrexate therapy, GVHD remains a serious and often fatal complication of marrow transplantation.

Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche

2004-07-01
Fumio Arai , Atsushi Hirao , Masako Ohmura +6 more
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Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair

2008-12-01
Anne Wilson , Elisa Laurenti , Gabriela Oser +7 more

Osteoblastic cells regulate the haematopoietic stem cell niche

2003-10-01
Laura M. Calvi , G. B. Adams , Kathryn Weibrecht +7 more
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SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells

2005-07-01
Mark J. Kiel , Ömer Yılmaz , Toshihide Iwashita +3 more
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Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoietic Microenvironment

2007-10-01
Benedetto Sacchetti , Alessia Funari , Stefano Michienzi +7 more
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Long-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell

1996-07-12
Masatake Osawa , Ken‐ichi Hanada , Hirofumi Hamada +1 more
Hematopoietic stem cells (HSCs) supply all blood cells throughout life by making use of their self-renewal and multilineage differentiation capabilities. A monoclonal antibody raised to the mouse homolog of CD34 … Hematopoietic stem cells (HSCs) supply all blood cells throughout life by making use of their self-renewal and multilineage differentiation capabilities. A monoclonal antibody raised to the mouse homolog of CD34 (mCD34) was used to purify mouse HSCs to near homogeneity. Unlike in humans, primitive adult mouse bone marrow HSCs were detected in the mCD34 low to negative fraction. Injection of a single mCD34(lo/-), c-Kit+, Sca-1(+), lineage markers negative (Lin-) cell resulted in long-term reconstitution of the lymphohematopoietic system in 21 percent of recipients. Thus, the purified HSC population should enable analysis of the self-renewal and multilineage differentiation of individual HSCs.
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Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone Marrow

2006-01-01
Yoshio Katayama , Michela Battista , Wei-Ming Kao +4 more
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Conditions controlling the proliferation of haemopoietic stem cells in vitro

1977-06-01
T. M. Dexter , Terence Allen , L. G. Lajtha
A liquid culture system is described whereby proliferation of haemopoietic stem cells (CFU-S), production of granulocyte precursor cells (CFU-C), and extensive granulopoiesis can be maintained in vetro for several months. … A liquid culture system is described whereby proliferation of haemopoietic stem cells (CFU-S), production of granulocyte precursor cells (CFU-C), and extensive granulopoiesis can be maintained in vetro for several months. Such cultures consist of adherent and non-adherent populations of cells. The adherent population contains phagocytic mononuclear cells, "epithelial" cells, and "giant fat" cells. The latter appear to be particularly important for stem cell maintenance and furthermore there is a strong tendency for maturing granulocytes to selectively cluster in and around areas of "giant fat" cell aggregations. By "feeding" the cultures at weekly intervals, between 10 to 15 "population doublings" of functionally normal CFU-S regularly occurs. Increased "population doublings" may be obtained by feeding twice weekly. The cultures show initially extensive granulopoiesis followed, in a majority of cases, by an accumulation of blast cells. Eventually both blast cells and granulocytes decline and the cultures contain predominantly phagocytic mononuclear cells. Culturing at 33 degrees C leads to the development of a more profuse growth of adherent cells and these cultures show better maintenance of stem cells and increased cell density. When tested for colony stimulating activity (CSA) the cultures were uniformly negative. Addition of exogenous CSA caused a rapid decline in stem cells, reduced granulopoiesis and an accumulation of phagocytic mononuclear cells.

Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signaling in Bone Marrow Stromal Cell Niches

2006-12-01
Tatsuki Sugiyama , Hiroshi Kohara , Mamiko Noda +1 more

Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective

2009-09-10
Marcie Tomblyn , Tom Chiller , Hermann Einsele +6 more
Tabled 1Table of ContentsAuthor List1143Preface1145Executive Summary1146Background to HCT1147Hematopoietic Cell Graft Safety1153Bacterial Infections1156Viral Infections1159Fungal Infections1170Regionally Limited or Rare Infections1176Infection Control and Prevention in Health care Facilities1182Safe Living after Transplantation1195Vaccinations1203References1207Appendices1229 Open table … Tabled 1Table of ContentsAuthor List1143Preface1145Executive Summary1146Background to HCT1147Hematopoietic Cell Graft Safety1153Bacterial Infections1156Viral Infections1159Fungal Infections1170Regionally Limited or Rare Infections1176Infection Control and Prevention in Health care Facilities1182Safe Living after Transplantation1195Vaccinations1203References1207Appendices1229 Open table in a new tab Marcie Tomblyn, University of Minnesota, Minneapolis, MN Tom Chiller, Centers for Disease Control and Prevention, Atlanta, GA Hermann Einsele, Universitatsklinik Wurzburg Medizinische Klinik und Poliklinik II, Wurzburg, Germany Ronald Gress, National Institutes of Health, Bethesda, MD Kent Sepkowitz, Memorial Sloan Kettering Cancer Center, New York, NY Jan Storek, University of Calgary, Calgary, Alberta, Canada John R Wingard, University of Florida, Gainesville, FL Jo-Anne H Young, University of Minnesota, Minneapolis, MN Michael A Boeckh, University of Washington Fred Hutchinson Cancer Research Center, Seattle, WA
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Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT

2005-07-01
Mohamed L. Sorror , Michael B. Maris , Rainer Storb +4 more
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Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects

2001-06-01
Peter A. McSweeney , Dietger Niederwieser , Judith A. Shizuru +7 more

The bone marrow niche for haematopoietic stem cells

2014-01-01
Sean J. Morrison , David T. Scadden
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Defining the Intensity of Conditioning Regimens: Working Definitions

2009-09-02
Andrea Bacigalupo , Karen K. Ballen , Doug Rizzo +7 more
Defining conditioning regimen intensity has become a critical issue for the hemopoietic stem cell transplant (HSCT) community. In the present report we propose to define conditioning regimens in 3 categories: … Defining conditioning regimen intensity has become a critical issue for the hemopoietic stem cell transplant (HSCT) community. In the present report we propose to define conditioning regimens in 3 categories: (1) myeloablative (MA) conditioning, (2) reduced-intensity conditioning (RIC), and (3) nonmyeloablative (NMA) conditioning. Assignment to these categories is based on the duration of cytopenia and on the requirement for stem cell (SC) support: MA regimens cause irreversible cytopenia and SC support is mandatory. NMA regimens cause minimal cytopenia, and can be given also without SC support. RIC regimens do not fit criteria for MA or NMA regimens: they cause cytopenia of variable duration, and should be given with stem cell support, although cytopenia may not be irreversible. This report also assigns commonly used regimens to one of these categories, based upon the agents, dose, or combinations. Standardized classification of conditioning regimen intensities will allow comparison across studies and interpretation of study results.
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Hematopoietic Stem-Cell Transplantation

2006-04-26
Edward A. Copelan
Hematopoietic stem-cell transplantation, which is used to treat both malignant and nonmalignant conditions, was first conceived more than 50 years ago, but problems associated with transplanting a nonsolid organ and … Hematopoietic stem-cell transplantation, which is used to treat both malignant and nonmalignant conditions, was first conceived more than 50 years ago, but problems associated with transplanting a nonsolid organ and modulating the immune response had to be solved before the procedure could be used clinically. This review summarizes background information about hematopoietic stem-cell transplantation and discusses the current role of the procedure.

Outcome of Cord-Blood Transplantation from Related and Unrelated Donors

1997-08-07
Éliane Gluckman , Vanderson Rocha , Agnès Boyer-Chammard +7 more
Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation.
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Methotrexate and Cyclosporine Compared with Cyclosporine Alone for Prophylaxis of Acute Graft versus Host Disease after Marrow Transplantation for Leukemia

1986-03-20
Rainer Storb , H. Joachim Deeg , John Whitehead +7 more
We treated 93 patients who had acute non-lymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated … We treated 93 patients who had acute non-lymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated total-body irradiation, followed by infusion of marrow from an HLA-identical sibling. To evaluate post-grafting prophylaxis for graft versus host disease, we studied these patients in a sequential, prospective, randomized trial that compared the effect of a combination of methotrexate and cyclosporine (n = 43) with that of cyclosporine alone (n = 50). All patients had evidence of sustained engraftment. A significant reduction in the cumulative incidence of grades II to IV acute graft versus host disease was observed in the patients who received both methotrexate and cyclosporine (33 percent), as compared with those who were given cyclosporine alone (54 percent) (P = 0.014). Seven patients who received cyclosporine alone acquired grade IV acute graft versus host disease, as compared with none who received both methotrexate and cyclosporine. Thirty-five of the 43 patients given both methotrexate and cyclosporine and 31 of the 50 patients given cyclosporine are alive as of this writing, at 4 months to 2 years (median, 15 months); the actuarial survival rates in the two groups at 1.5 years were 80 percent and 55 percent, respectively (P = 0.042). We conclude that the combination of methotrexate and cyclosporine is superior to cyclosporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival. (N Engl J Med 1986; 314:729–35.)

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report

2014-12-19
Madan Jagasia , Hildegard Greinix , Mukta Arora +7 more
The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework … The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies.
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Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Diseases

1998-02-01
Shimon Slavin , Arnon Nagler , E Naparstek +7 more
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Bone Marrow Transplant

2001-01-01
Patrick HC Tan

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report

2005-12-01
Alexandra H. Filipovich , Daniel J. Weisdorf , Steven Z. Pavletic +7 more
This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) … This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least 1 distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy be considered for patients who meet criteria for chronic GVHD of moderate to severe global severity.
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Bone marrow transplant

1999-03-01
Jeff Szer

Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Diseases

1998-02-01
Shimon Slavin , Arnon Nagler , E Naparstek +7 more
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HETEROTOPIC TRANSPLANTS OF BONE MARROW

1968-03-01
A. J. Friedenstein , K. V. Petrakova , ALEXANDRA IVANOVNA KUROLESOVA +1 more
In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the … In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the initial donor line. In syngeneic and semisyngeneic grafts of bone marrow under the renal capsule bone and bone marrow are formed. In allogeneic grafts only bone is formed; this bone is subsequently resorbed. In 14-month semisyngeneic transplants the bone marrow consists of recipient cells. This is true for both the proliferating pool and the stem cells of hematopoietic tissue. At the same time, osteogenic precursor cells and bone tissue in these transplants are of donor origin. A discussion is presented of the interrelationship between determinated osteogenic precursor cells (preosteoblasts) and hematopoietic stem cells (or their descendants) in which osteogenesis is inducible.

Bone Marrow Transplant

1990-06-01
Rosemary Ford , Seth Eisenberg

Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients

1990-12-15
H-J Kolb , J. Mittermüller , Ch. Clemm +5 more
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Bone-Marrow Transplantation

1975-04-17
E. Donnall Thomas , Rainer Storb , Clift Ra +6 more
THE modern era of bone-marrow transplantation was ushered in by the experiments of Jacobsen, Lorenz and their colleagues, who showed that mice could be protected against otherwise lethal irradiation by … THE modern era of bone-marrow transplantation was ushered in by the experiments of Jacobsen, Lorenz and their colleagues, who showed that mice could be protected against otherwise lethal irradiation by shielding of the spleen1 or by intravenous infusion of marrow.2 At first it was thought that this protective effect was due to a humoral factor.3 By 1956, however, several laboratories, using a variety of blood genetic markers, demonstrated that the protective effect against lethal irradiation was due to the colonization of the recipient marrow by donor cells.4 5 6 7An article on clinical marrow transplantation that appeared in . . .

Hematopoietic stem cell transplantation outcomes in pediatric acquired aplastic anemia with inherited bone marrow failure syndrome-associated genes

2025-06-25
Zhaohe Jing , Longshuan Zhao , Yumiao Mai +4 more | Bone Marrow Transplantation

Prognostic factors of survival in second allogeneic hematopoietic transplantation

2025-06-24
Rodrigo Cantera Estefanía , Raquel García Ruiz , Sara Fernández-Luis +7 more | Annals of Hematology
Allogeneic stem cell transplantation (alloSCT) remains a potentially curative treatment for patients with hematologic malignancies. Nevertheless, relapse and graft failure continue to be major barriers to long-term success. In these … Allogeneic stem cell transplantation (alloSCT) remains a potentially curative treatment for patients with hematologic malignancies. Nevertheless, relapse and graft failure continue to be major barriers to long-term success. In these high-risk situations, a second alloSCT may represent the only curative option, although outcomes are frequently compromised by high non-relapse mortality and disease progression. Despite improvements in conditioning regimens, donor availability, and supportive care strategies, clinical results remain suboptimal and underscore the importance of careful patient selection.In this study, we report the 15-year experience of our institution-a national reference center for alloSCT in Spain-in managing patients undergoing a second alloSCT. Our objective is to evaluate relevant clinical and transplant-related factors associated with survival outcomes. Ultimately, we aim to enhance the selection process and contribute to a more personalized approach to 2nd-alloSCT, helping clinicians make better-informed decisions about which patients are most likely to benefit from this high-risk but potentially life-saving procedure.

Interesting Images: Endocytoscopy for In Vivo Diagnosis of Intestinal Graft-Versus-Host Disease

2025-06-24
Timo Räth , Till Orlemann , Francesco Vitali +3 more | Diagnostics
Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach … Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach can be limited by thrombocytopenia accompanying aSCTx and the diagnostic delay associated with routine histopathology. Here, we report on two patients in which dye-based contact microscopy using a latest generation endocytoscope with 520-fold magnification enabled in vivo diagnosis of GvHD. The first patient was a 23-year-old man with acute lymphoblastic leukemia presenting with non-bloody diarrhea 3 months after aSCTx. After topical staining with crystal violet and methylene blue, endocytoscopy in the rectum showed several apoptotic epithelial cells. Histopathology confirmed GvHD grade III according to the Lerner classification. The second patient was a 59-year-old female with diarrhea 3 months after aSCTx. Apart from pathognomic apoptotic bodies, EC additionally revealed crypt lumina enlargement and mononuclear cell infiltrates in the lamina propria with subsequent crypt distension. The duration of the procedure was less than 5 min in each patient. These findings illustrate that in vivo microscopy using endocytoscopy can enable instantaneous diagnosis of GvHD with the benefit of accelerating therapeutic decisions in patients with suspected severe GvHD.

CK2α Deletion in the Hematopoietic Compartment Shows a Mild Alteration in Terminally Differentiated Cells and the Expansion of Stem Cells

2025-06-24
Rajesh Rajaiah , Muhammad Daniyal , Marudhu Pandiyan Shanmugam +7 more | Cells
Casein Kinase II (CK2) is a ubiquitously present serine/threonine kinase essential for mammalian development. CK2 holoenzyme is a tetramer with two highly related catalytic subunits (α or α’) and two … Casein Kinase II (CK2) is a ubiquitously present serine/threonine kinase essential for mammalian development. CK2 holoenzyme is a tetramer with two highly related catalytic subunits (α or α’) and two regulatory ß subunits. Global deletion of the α or β subunit in mice is embryonically lethal. We and others have shown that CK2 is overexpressed in leukemia cells and plays an important role in cell cycle, survival, and resistance to the apoptosis of leukemia stem cells (LSCs). To study the role of CK2α in adult mouse hematopoiesis, we generated hematopoietic cell-specific CK2α-conditional knockout mice (Vav-iCreCK2 f/f). Here we report the generation and validation of a novel mouse model that lacks CK2α in the hematopoietic compartment. Vav-iCreCK2α f/f mice were viable without dysmorphic features and showed a mild phenotype under baseline conditions. In Vav-iCreCK2α f/f mice, the blood count showed a significant decrease in total red blood cells and platelets. The spleen was enlarged in Vav-iCreCK2α f/f mice with evidence of extramedullary hematopoiesis. HSC and early progenitor cell compartments showed expansion in CK2α-null bone marrow, suggesting that the absence of CK2α impaired their proliferation and differentiation. Given the established roles of CK2 in cell cycle regulation and the findings reported here, further functional studies are warranted to investigate the role of CK2α in HSC self-renewal and differentiation. This mouse model serves as a valuable tool for understanding the role of CK2α in normal and malignant hematopoiesis.

Upfront Alternative Donor HCT in Severe Aplastic Anemia: Gaps and Opportunities to Translate Evidence into Practice

2025-06-24
Neel S. Bhatt , Azra Borogovac , Yvonne A. Efebera +7 more | Blood Advances

A prospective clinical trial of GVHD prophylaxis with Post-Transplant Cyclophosphamide and Abatacept

2025-06-24
Divya Koura , Kaitlyn C Dykes , Aaron M. Goodman +7 more | Blood Advances

Cryopreservation of CD34+ Hematopoietic Stem Cells Using Cryofit® DMSO and Its Outcomes

2025-06-23
Semih Başçı , Hikmettullah Batgi , Sinem Namdaroğlu | Hitit Medical Journal
Objective: Autologous hematopoietic stem cell transplantation (auto-SCT) is a key treatment for hematological malignancies and immune disorders. Cryopreservation of CD34+ hematopoietic stem cells (HSCs) ensures transplant success. Dimethyl sulfoxide (DMSO) … Objective: Autologous hematopoietic stem cell transplantation (auto-SCT) is a key treatment for hematological malignancies and immune disorders. Cryopreservation of CD34+ hematopoietic stem cells (HSCs) ensures transplant success. Dimethyl sulfoxide (DMSO) is a widely used cryoprotectant but can cause infusion-related toxicities. CryoFit® DMSO aims to enhance cell viability while reducing adverse effects. This study evaluates its efficacy and safety in auto-SCT. Material and Method: A single-center, retrospective study was conducted on 80 patients who underwent auto- SCT with CD34+ HSCs cryopreserved using CryoFit® DMSO. Mobilization was performed using granulocyte colony-stimulating factor (G-CSF) ± chemotherapy and plerixafor when required. CD34+ cells were quantified via flow cytometry before cryopreservation. Post-transplant engraftment, transfusion needs, and infusion-related side effects were assessed. Data analysis was conducted using SPSS 26.0. Results: The median patient age was 58.5 years (range: 19-75) and 53.8% (n=43) of the cohort sample was female. Multiple myeloma was the most common diagnosis (57.5%). The median collected CD34+ cell count was 5.8 x 106/ kg (range: 3.2-14). Post-thaw viability was 98% (range: 90-99.5%). Neutrophil and platelet engraftment occurred at medians of 13 and 17 days, respectively. The median hospitalization duration was 24 days (range: 15-60). Infusion-related adverse effects occurred in 26.3% of patients, primarily nausea/vomiting (15%), all manageable. Conclusion: CryoFit® DMSO effectively preserves CD34+ HSCs with high post-thaw viability and favorable engraftment. Mild infusion-related toxicities were observed but were transient. The results support its continued use in auto-SCT. Further multicenter studies are required to optimize cryopreservation protocols.

Impact of HLA eplets mismatch load on outcomes of outpatient haploidentical-related stem cell transplantation from peripheral blood after reduced intensity conditioning

2025-06-23
José Carlos Jaime‐Pérez , Magali Irais Ureño-Segura , Adriana Domínguez-Villanueva +3 more | Expert Review of Hematology
Molecular typing before hematopoietic stem cell transplantation (HSCT) at the eplet level is an emerging method to optimize HLA matching. Patients who received outpatient haploidentical HSCT (Haplo-HSCT) from a sibling … Molecular typing before hematopoietic stem cell transplantation (HSCT) at the eplet level is an emerging method to optimize HLA matching. Patients who received outpatient haploidentical HSCT (Haplo-HSCT) from a sibling after reduced intensity conditioning (RIC) were studied. HLA class I and II mismatched eplets (MEs) load was determined using HLAMatchmaker software. A cutoff > or < 10 MEs was used to assess outcomes. 114 patients were studied. A locus B MEs load > 10 was associated with decreased overall survival (OS), (p = 0.049), increased graft failure (GF) (p = 0.004). Mortality was higher with > 10 MEs in HLA-I locus B (p = 0.025), and HLA-II DRB1 (p = 0.026); chronic GVHD was higher with > 10 MEs in DRB1 (p = 0.009). Anti-HLA donor-specific antibodies (DSA) were more frequent in recipients with > 10 MEs load at locus C (p = 0.021) and DRB1 (p = 0.002). MEs load > 10 at locus C and DRB1 were associated with anti-HLA DSA. Infection (p = 0.012), DSA (p = 0.014), and relapse (p = 0.001) were associated with lower OS, while multitransfusion (p = 0.035), aGVHD (p = 0.035) and infection (p = 0.021) with reduced event-free survival (EFS). HLA MEs load > 10 in locus B was associated with reduced OS, and in locus DRB1 with higher death rate and cGVHD after outpatient sibling haplo-HSCT using RIC.

JAK2 Inhibitors and Emerging Therapies in Graft-Versus-Host Disease: Current Perspectives and Future Directions

2025-06-23
Behzad Amoozgar , Ayrton Bangolo , Abdifitah Mohamed +4 more | Biomedicines
Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. … Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. Central to GVHD pathophysiology is the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, where JAK2 mediates key pro-inflammatory cytokines, including IL-6, IFN-γ, and GM-CSF. These cytokines promote donor T cell activation, effector differentiation, and target organ damage. The introduction of ruxolitinib, a selective JAK1/2 inhibitor, has transformed the treatment landscape for steroid-refractory acute and chronic GVHD, leading to improved response rates and durable symptom control. However, its limitations—such as cytopenias, infectious complications, and incomplete responses—have catalyzed the development of next-generation agents. In 2024, the FDA approved axatilimab, a CSF-1R inhibitor that targets monocyte-derived macrophages in fibrotic chronic GVHD, and remestemcel-L, an allogeneic mesenchymal stromal cell therapy, for pediatric steroid-refractory acute GVHD. Both agents offer mechanistically distinct and clinically meaningful additions to the therapeutic armamentarium. In parallel, emerging combination strategies involving JAK2 inhibitors and novel biologics show promise in enhancing immune tolerance while preserving graft-versus-leukemia (GvL) effects. Recent advances in biomarker development, such as the MAGIC Algorithm Probability (MAP), are enabling early risk stratification and response prediction. The integration of these tools with organ-specific and personalized approaches marks a shift toward more precise, durable, and tolerable GVHD therapy. This review highlights the current state and future direction of JAK2 inhibition and complementary therapies in the evolving GVHD treatment paradigm.

Model‐Informed Precision Dosing of Busulfan for Children and Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Critical Evaluation of Current <scp>PK</scp> Models and Dose Recommendations

2025-06-22
Rashudy F. Mahomedradja , Tim Bognàr , Kaj E. van Schie +7 more | Clinical Pharmacology & Therapeutics
Busulfan is administered intravenously in conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT), with model‐informed precision dosing (MIPD) targeting a 4‐day cumulative AUC of 80–100 mg*hour/L. Three pharmacokinetic … Busulfan is administered intravenously in conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT), with model‐informed precision dosing (MIPD) targeting a 4‐day cumulative AUC of 80–100 mg*hour/L. Three pharmacokinetic (PK) models—Bognar, Langenhorst, and McCune—were evaluated using data with a minimum of 1 and a median of 2 PK sampling days from pediatric and adult patients at two tertiary hospitals in the Netherlands. Simulations with the best‐performing model evaluated dose optimization and the role of therapeutic drug monitoring (TDM). The Bognar and Langenhorst models, with overlapping datasets (25% between models, 21% with the current), accurately described busulfan concentration‐time curves in all 535 patients (0.18–72 years), especially in those &gt; 60 years (bias and precision in clearance; −5.6%, 6.48% and 16.55%, 16.95%; in observed concentrations −1.86%, −6.52% and 9.12%, 3.58% for both models &gt; 60 years). The McCune model underestimated clearance by 36% in children &lt; 2 years of age. Despite accounting for age‐dependent glutathione depletion, the Langenhorst model did not outperform the simpler Bognar model. Model‐based initial dosing did not improve target attainment over SmPC‐based dosing. However, TDM‐based MIPD with a single TDM on days 2–4 significantly improved target attainment (49% vs. 87%), with a number needed to treat for TDM of 2.5. This study demonstrates the clinical efficacy of simple PK models such as the Bognar model, providing that simplicity does not compromise performance. It highlights the inadequacy of nomogram‐based dosing alone and reinforces the critical role of TDM in optimizing busulfan exposure for pediatric and adult myeloablative HSCT patients.

Fludarabine – Total Body Irradiation-Based Myeloablative Conditioning for Haploidentical Hematopoietic Stem Cell Transplantation: A 10-Year Single Centre Real-World Analysis

2025-06-20
Pragadeesh Thamarai Selvan , Krishnarathinam Kannan , Jayachandran Perumal Kalaiyarasi +6 more | Indian Journal of Hematology and Blood Transfusion

Outcomes of Matched Sibling and Haploidentical Donors Hematopoietic Stem Cell Transplantation for Pediatric Severe Aplastic Anemia: A Retrospective Multicenter Study

2025-06-20
Diego Medina , Natalia Builes , A. Franco +7 more | Hematology/Oncology and Stem Cell Therapy

Artificial intelligence-based predictive model for relapse in acute myeloid leukemia patients following haploidentical hematopoietic cell transplantation

2025-06-20
Shuang Fan , Haoyang Hong , Shengye Lu +7 more | Journal of Translational Internal Medicine
Abstract Background and Objectives Relapse is one of the most critical causes of transplant failure in patients with acute myeloid leukemia (AML) receiving haploidentical-related donor (HID) hematopoietic stem cell transplantation … Abstract Background and Objectives Relapse is one of the most critical causes of transplant failure in patients with acute myeloid leukemia (AML) receiving haploidentical-related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to develop an artificial intelligence (AI)-based predictive model for post-transplant relapse in patients with AML receiving HID HSCT. Methods This study included patients with consecutive AML (aged ≥ 12 years) receiving HID HSCT in complete remission (CR). We randomly selected 70% of the entire population ( n = 665) as the training cohort for developing the model and nomogram, which were both evaluated using data from the remaining 30% of the patients (validation cohort, n = 286). Furthermore, the model was validated in an independent cohort ( n = 213) and in the clinical practice of five experienced clinicians. Results Five variables (AML risk category, number of courses of induction chemotherapy for first CR, disease status, measurable residual disease before HSCT, and blood group disparity) were included in the final model ( i.e ., PKU-AML model). The concordance index of the nomogram was 0.707. The Hosmer−Lemeshow test showed a good fit for this model ( P = 0.205). The calibration curve was close to the ideal diagonal line, and decision curve analysis showed a significantly better net benefit for this model. The reliability of our prediction nomogram was demonstrated in a validation cohort, an independent cohort, and in clinical practice. Conclusions Our PKU-AML model can predict the relapse of patients with AML receiving HID HSCT in CR, providing an effective tool for the early prediction and timely management of post-transplant relapse.

Critical care illness in allogeneic hematopoietic stem-cell transplantation recipients with chronic graft versus host disease

2025-06-20
Dara Chean , Romy Younan , Thibault Dupont +7 more | Critical Care
Chronic graft-versus-host disease (cGVHD) is a leading long-term complication following allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). However, its impact on outcomes in critically ill Allo-HSCT recipients has little been evaluated. We … Chronic graft-versus-host disease (cGVHD) is a leading long-term complication following allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). However, its impact on outcomes in critically ill Allo-HSCT recipients has little been evaluated. We conducted a post hoc analysis of a multicenter cohort study involving Allo-HSCT recipients admitted to 14 French intensive care units (ICUs) between January 1, 2015, and December 31, 2020. The primary endpoint was 90-day mortality after admission. The prevalence of cGVHD was 10% (114/1164), with a severe form of the disease in half the patients. The most common manifestation was skin involvement (94%), followed by gastrointestinal tract (56%), liver (28%), and lungs (19%). The primary reason for ICU admission was acute respiratory failure (43%), with 65% of patients presenting with multi-organ dysfunction. Overall survival was 61% at 90 days and 40% at 3 years. The Sequential Organ Failure Assessment score at ICU admission was the only independent predictor of 90-day mortality (HR/point 1.32 [95% CI 1.21-1.46]; p < 0.01). cGVHD severity did not significantly influence survival. Patients with cGVHD had comparable survival rates to those with controlled acute GVHD or without GVHD (90-day: 61% vs. 55% and 66%; 3-year: 40% vs. 32% and 47%). In critically ill Allo-HSCT recipients, the presence or severity of cGVHD is not associated with survival and should not influence the decision to admit or not the patient to the ICU. However, careful discussions about the goals of care should be undertaken in patients with severe hepatic or pulmonary involvement. Retrospectively registered.

The impact of second allogeneic hematopoietic stem cell transplantation as salvage therapy for hematologic diseases after a first allogeneic transplantation

2025-06-20
Hikmetullah Batgi , Tuğba Zorlu , Mehmet Ali Erkurt +7 more | Transfusion and Apheresis Science

The Effect of Threosulfan-based versus Busulfan-based Preparation Regimens on Transplant Outcomes

2025-06-20
Burcu Aslan Candir , Nazik Okumus , İpek Yönal Hindilerden +7 more | Transfusion and Apheresis Science

Acute and chronic graft-versus-host disease treatment and management in the Eastern Mediterranean region: A Worldwide Network for Blood and Marrow Transplantation survey

2025-06-20
Ibrahim N. Muhsen , Dietger Niederwieser , Laurent Garderet +7 more | Hematology/Oncology and Stem Cell Therapy

Exposure‐Response Relationships for Axatilimab in Patients with Chronic Graft‐Versus‐Host Disease

2025-06-19
Yan‐ou Yang , Alina Volkova , Victor Sokolov +5 more | Clinical Pharmacology & Therapeutics
Axatilimab, a high‐affinity humanized monoclonal antibody that targets colony‐stimulating factor 1 receptor, is approved for the treatment of chronic graft‐versus‐host disease (cGVHD). Here, we describe the exposure‐response relationships for efficacy … Axatilimab, a high‐affinity humanized monoclonal antibody that targets colony‐stimulating factor 1 receptor, is approved for the treatment of chronic graft‐versus‐host disease (cGVHD). Here, we describe the exposure‐response relationships for efficacy and safety in patients with cGVHD who received axatilimab. Exposure‐efficacy relationships were assessed in treated patients in the AGAVE‐201 study ( n = 239); exposure‐safety relationships were assessed in treated patients in AGAVE‐201 ( n = 239) and the phase 1/2 SNDX‐6352‐0503 study ( n = 39). For binary or time‐to‐event endpoints, logistic or Cox regression analyses, respectively, were performed using axatilimab exposure metrics that were derived from a previously developed population pharmacokinetic/pharmacodynamic model. Overall response and ≥ 7‐point improvement in modified Lee Symptom Scale responses were associated with axatilimab exposure, with lower axatilimab exposure increasing the odds of a response. Duration of response was not associated with axatilimab exposure. Ten of 11 safety endpoints were associated with axatilimab exposure, with higher axatilimab exposure increasing the odds of adverse events. Among the 3 regimens evaluated in AGAVE‐201, the 0.3 mg/kg once every 2 weeks (Q2W) regimen had the highest predicted probability of response. Additionally, this dose group had the lowest predicted probability of event occurrence across all 10 safety endpoints associated with exposure among the evaluated regimens. Despite body weight influencing axatilimab exposure by &gt; 20%, its effect on efficacy and safety endpoints remained minimal, with a maximum difference of ≤ 0.4% and ≤ 4.4% between the 1st and 4th quartiles of body weight, respectively. Taken together, these findings support the benefit–risk profile of axatilimab 0.3 mg/kg Q2W in patients with cGVHD.

<scp>MRD</scp> and <scp>NK</scp>‐Cell Chimerism Predict Transplant Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

2025-06-19
Xing Chen , Huihong Huang , Wei-Hao Chen +7 more | American Journal of Hematology
Monitoring NK-cell chimerism serves as a valuable addition to MRD-based surveillance. Monitoring NK-cell chimerism serves as a valuable addition to MRD-based surveillance.

Circadian fluctuation of soluble CD26 dictates the impact of the timing of cord blood transplantation on acute graft-versus-host disease

2025-06-19
Xiaoyu Zhu , Yue Wu , Yiwen Hou +7 more | Research Square (Research Square)
<title>Abstract</title> Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cornerstone treatment to cure many malignant and nonmalignant hematological diseases. Our recent research demonstrated that early-day stem cell infusions significantly reduce … <title>Abstract</title> Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cornerstone treatment to cure many malignant and nonmalignant hematological diseases. Our recent research demonstrated that early-day stem cell infusions significantly reduce the incidence and severity of acute graft-versus-host disease (aGVHD) following allo-HSCT. However, the effect of infusion timing on aGVHD in cryopreserved unrelated cord blood transplantation (UCBT) remains unclear. Here, we show that early morning cord blood infusions significantly reduce aGVHD severity and improve survival. We found that circadian variations in cytokines, particularly soluble CD26 (sCD26), correlate with the severity of aGVHD. Inhibiting the enzymatic activity of sCD26 with Sitagliptin significantly mitigated aGVHD and improved survival in late-infused mice. Our study indicates that scheduling UCBT in the early morning could be a simple and effective prophylactic strategy for aGVHD and that inhibiting sCD26 could be a promising therapeutic approach for late infusions.

Impact of Hyperbaric Oxygen on Post-UCB Transplant Blood Transfusion and Growth Factor Support

2025-06-19
Haitham Abdelhakim , Ahmed Hebishy , Leyla Shune +5 more | Transfusion and Apheresis Science

Efficacy and safety of rabbit ATLG and ATG in allogeneic hematopoietic stem cell transplantation for children with acquired severe aplastic anemia

2025-06-19
Senlin Zhang , Qi Ji , Li Gao +7 more | Annals of Hematology
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome characterized by bone marrow hypoplasia and peripheral blood cytopenia. Without timely treatment, it frequently proves fatal. Rabbit anti-thymocyte globulin … Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome characterized by bone marrow hypoplasia and peripheral blood cytopenia. Without timely treatment, it frequently proves fatal. Rabbit anti-thymocyte globulin (ATG) and anti-human T lymphocyte globulin (ATLG) are widely used for graft-versus-host disease (GVHD) prophylaxis. However, their comparative efficacy in pediatric SAA remains undetermined. This study involved a single-center retrospective analysis of two ATG preparations in pediatric patients undergoing allo-HSCT. The primary endpoint was the incidence of GVHD and viral reactivation following HSCT. Secondary endpoints included overall survival (OS), GVHD-free and failure-free survival (GFFS), neutrophil engraftment, platelet engraftment, hemorrhagic cystitis (HC), tolerability, and toxicities within each group. A total of 124 pediatric SAA patients who underwent their first allo-HSCT between January 2019 and March 2024 were enrolled, with 35 receiving ATLG and 89 receiving ATG. OS, GFFS, GVHD, and HC incidence were comparable between the ATLG and ATG groups (OS: 95.2% vs. 92.9%, P = 0.617). ATLG significantly reduced the incidence of 180-day CMV (45.7% vs. 74.2%, P = 0.0062) and EBV reactivation (29.8% vs. 52.8%, P = 0.025). Additionally, ATLG was associated with fewer adverse events (AEs), including fever (P = 0.009) and rash (P = 0.018). ATLG demonstrated comparable efficacy to ATG in preventing GVHD and achieving OS in pediatric SAA patients undergoing allo-HSCT, while significantly reducing viral reactivation and AEs. These findings support ATLG as a safer alternative, warranting further prospective studies.

Randomized trial of anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide to prevent graft-versus-host disease in haploidentical transplantation

2025-06-19
Zheng‐Li Xu , Tingting Han , Xiaolu Zhu +7 more | Haematologica
The combination of anti-thymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) appears to be a potentially effective graft-versus-host disease (GVHD) prevention strategy for haploidentical transplantation. However, the majority of the evidence … The combination of anti-thymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) appears to be a potentially effective graft-versus-host disease (GVHD) prevention strategy for haploidentical transplantation. However, the majority of the evidence originated from retrospective studies without uniform protocols. Our previous findings indicated that 10 mg/kg ATG plus low-dose PTCy could decrease GVHD among high-risk populations transplanted from maternal or collateral relatives. We designed an open-label, phase III, randomized controlled trial to compare patients receiving granulocyte colony-stimulating factor (G-CSF)/ATG-based haploidentical transplantation with or without low-dose PTCy (14.5 mg/kg on days 3 and 4) in nonmaternal, noncollateral haploidentical transplants from fathers, children or siblings. A total of 66 patients were randomly assigned to ATG-PTCy (n=44) or ATG (n=22) when the first interim analysis was performed. The interim analysis revealed that the 100-day cumulative incidences (CI) of grade II-IV (18.2% [95% CI 6.6-29.7] vs. 18.2% [1.7-34.7]; P = 0.996) and III-IV acute GVHD (2.3% [95% CI 0-6.7] vs. 0; P = 0.480) were comparable between the ATG-PTCy and ATG cohorts, as was chronic GvHD at 1 year. The estimated 1-year disease free survival (DFS) rates were also similar between ATG-PTCy and ATG cohorts (95.5% [95% CI 89.5–100] vs. 95.2% [86.6–100]; P = 0.979). These results suggested that ATG/PTCy (low-dose) had no advantage over 10 mg/kg ATG-based prophylaxis in patients with haploidentical transplantation other than that of maternal donors or collateral relatives. Future work needs to focus on identifying which populations might benefit from the combined strategy in the context of G-CSF/ATG-based protocols.

Intensified conditioning with high-dose total marrow irradiation and myeloablative chemotherapy reduces risk of relapse without increasing toxicity in allogeneic hematopoietic stem cell transplant for high-risk myeloid malignancies: a phase II study

2025-06-19
Lucas Maahs , Ana Maria Heuminski de Ávila , Matthew Koshy +7 more | Haematologica
The intensity of the conditioning regimen in hematopoietic stem cell transplantation (HSCT) correlates with the risk of relapse, however its potential benefit may be outweighed by the associated risk of … The intensity of the conditioning regimen in hematopoietic stem cell transplantation (HSCT) correlates with the risk of relapse, however its potential benefit may be outweighed by the associated risk of toxicity. The addition of total marrow irradiation (TMI) to myeloablative conditioning provides an opportunity to increase intensity with minimal additional toxicity. In this phase 2 clinical trial, 30 patients with high-risk myeloid malignancies received an allogeneic HSCT using myeloablative TMI at 9Gy in combination with standard myeloablative fludarabine/intravenous busulfan (FluBu4) chemotherapy. The study included patients with matched-related donors (n=10) receiving TMI/FluBu4 and patients with matched unrelated (n=14) or 1-antigen mismatched unrelated (n=6) donors receiving TMI/FluBu4 and rabbit antithymocyte globulin. All patients achieved sustained engraftment. Grade 3-4 extramedullary toxicities were: mucositis in 59% (n=17), nausea/vomiting in 10% (n=3) and diarrhea in 7% (n=2) of the patients. Acute graft-versus-host disease (GVHD) grade III-IV was seen in 4 patients (13.3%). Moderate/severe chronic GVHD was observed in 11 patients (36.7%). With a median follow-up of 1483 days (range: 63-2260 days) for patients alive, the overall survival and disease-free survival at 1 year were 72.4% and 65.5%, respectively. GVHD-Free Relapse-Free Survival at 1-year was 41.4%. Of 30 patients in the study, 6 relapsed/progressed (20%) and 5 of them died of the disease (16.7%); whereas 6 patients (20%) died of transplant-related mortality. We conclude that a myeloablative regimen with TMI at 9Gy and FluBu4 was well tolerated and achieved encouraging results in patients with myeloid malignancies at high risk of relapse (clinicaltrials.gov Identifier: NCT03121014).

High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation

2025-06-18
Andrej Pešić , Nevena Bešević , Nicolaus Kröger +7 more | Frontiers in Immunology
Introduction Immune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) … Introduction Immune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) and relapse. However, data on the impact of different lymphocyte subsets influencing outcomes is conflicting. Furthermore, the importance of immune reconstitution parameters in patients previously not experiencing major post-transplant complications is lacking. Methods We evaluated the clinical impact of day 90 NK cell, CD4 + T-cell, CD8 + T-cell, B-cell, and NKT cell counts on transplant outcomes by performing a landmark analysis in event-free patients. Lymphocyte subset counts were obtained from 70 patients undergoing in vivo T-cell depleted allogeneic transplantation from 2018 to 2024. Patients eligible for the study experienced no acute GvHD, poor graft function, graft failure, or relapse in the first three months after transplantation-prior to obtaining IR data. We associated lymphocyte subset counts to overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse (RI), and secondary graft failure/poor graft function. Results High NK cell counts on day 90 (&amp;gt;178/μL) were associated with improved OS (P=0.039) and lower rates of NRM (1-year cumulative incidence of 5.7% versus 31.4%, HR 0.16, 95% CI 0.04-0.69, P=0.014). A protective effect on RI was not found. We found no patient, disease or transplant-related variables to be significantly associated with day 90 NK cell counts. Conclusion The results suggest that high NK cell counts on day 90 after T-cell depleted allogeneic transplantation independently protect from NRM and improve OS in patients without prior major post-transplant complications.

A prior status of graft‐versus‐host disease affects donor lymphocyte infusion outcomes in patients with relapsed haematological malignancies after allogeneic stem cell transplantation

2025-06-18
Claudia Mae Velasco , Yoshitaka Inoue , Joseph Cioccio +7 more | British Journal of Haematology
Summary Optimizing the effectiveness of donor lymphocyte infusion (DLI) for relapse after allogeneic stem cell transplantation (alloHSCT) has been challenging. We investigated whether the benefits of achieving full donor chimerism … Summary Optimizing the effectiveness of donor lymphocyte infusion (DLI) for relapse after allogeneic stem cell transplantation (alloHSCT) has been challenging. We investigated whether the benefits of achieving full donor chimerism (FDC) and developing graft‐versus‐host disease (GVHD) after DLI are affected by a history of GVHD before DLI. We retrospectively analysed 56 patients who received DLI for relapse after alloHSCT at our institute from 2015 to 2022. Among 29 patients without GVHD before DLI, those who achieved FDC after DLI had a significantly higher 1‐year overall survival (OS) compared to those who did not (73.7% vs. 20.0%; p &lt; 0.001). Furthermore, in the same cohort, patients who developed GVHD after DLI showed a tendency towards higher OS compared to those who did not (60.0% vs. 52.6%; p = 0.067). In contrast, in patients with GVHD before DLI, there was no significant difference in OS between patients with or without achieving FDC (64.3% vs. 33.3%, p = 0.226) or developing GVHD (60.0% vs. 53.3%, p = 0.866). Our study showed that achieving FDC or developing GVHD after DLI improved OS, but only in those without a prior history of GVHD. The graft‐versus‐leukaemia effect may be better exploited in patients without a history of GVHD.

New perspectives on extracorporeal life support: expert teams and precise selection of candidates are transforming pediatric cancer and hematopoietic cell transplantation care

2025-06-18
Caitlin Hurley , Matteo Di Nardo , Matthew G. Rees +7 more | Frontiers in Oncology
Extra Corporeal Life Support (ECLS) for pediatric oncology and stem cell transplant patients over the past two decades has made progress. Substantial improvements in ECLS, Continuous Renal Replacement Therapy (CRRT), … Extra Corporeal Life Support (ECLS) for pediatric oncology and stem cell transplant patients over the past two decades has made progress. Substantial improvements in ECLS, Continuous Renal Replacement Therapy (CRRT), and mechanical ventilation techniques, along with enhanced anticoagulation management and infection control, have contributed to better patient outcomes. Additionally, advancements in HLA matching, donor selection, and the management of chemotherapy and transplant complications have further improved survival rates. The authors propose establishing an expert team and a standardized process to evaluate ECLS candidacy, addressing past controversies and optimizing outcomes for this vulnerable population. The criteria for candidacy have evolved significantly, necessitating expert evaluation.

Long-Term Results of Hematopoietic Cell Transplantation (HCT) for Adults with Blood Disorders– A Systematic Review

2025-06-18
Kajetan Karaszewski , Jakub Góra , Weronika Ploch +1 more | Stem Cell Reviews and Reports
Both autologous and allogeneic stem cell transplantations are widely used as a standard of care or significant clinical option in treating various malignant and non-malignant diseases of the hematopoietic system. … Both autologous and allogeneic stem cell transplantations are widely used as a standard of care or significant clinical option in treating various malignant and non-malignant diseases of the hematopoietic system. The value of these treatment methods would be better assessed through the review of long-term progression-free and overall survival (PFS and OS) rates, which are highly dependent on the primary diagnosis and stage of disease at the time of transplantation as well as on the specific type of used transplantation procedure. While the best (over 90%) 5-, 10- and 15-year survival rates are achieved in children with genetic errors after HLA-matched allogeneic transplantation, in adults these results are worse. Intermediate results (50-80%) of 5- and 10-year survival rates are obtained in malignancies transplanted in complete remission, and the worst (between 10 and 30%) 5- and 10-year survival rates are seen in malignancies transplanted without remission. However, none of the other treatment methods in these latter situations allows to obtain any long-term survival. In conclusion, transplantation of hematopoietic cells is a group of therapeutic methods with unprecedented effectiveness in reversing outcome of deadly disorders of the hematopoietic system. Moreover, its therapeutic effect is usually maintained for 10 years or more.

Preformed anti-HLA DQA1/DQB1 DSA possibly responsible for graft failure in haploidentical stem cell transplantation

2025-06-18
H. H. Wang , Jing Cheng , Fan Zhang +1 more | Expert Review of Hematology
Primary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplants (HSCT) and is associated with poor outcomes. Most clinical studies have focused on donor-specific anti-HLA antibodies … Primary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplants (HSCT) and is associated with poor outcomes. Most clinical studies have focused on donor-specific anti-HLA antibodies (DSAs) against HLA-A, -B, and -DR molecules. We present the first reported case of PGF associated with a preformed high-level DSA against HLA-DQ alone. The 39-year-old patient was diagnosed with acute myeloid leukemia. She received a haploidentical graft from her son and suffered PGF. She had persistently high levels of DSAs against her son's HLA-DQA1 and HLA-DQB1 molecules after desensitization. No alternative donor was available. To circumvent the second graft failure, we adopted an approach of combining two units of unrelated cord blood (CB) and G-CSF-primed bone marrow (BM) and peripheral blood stem cells (PBSCs) from her son's transplants. The BM short tandem repeats (STRs) assay showed that one unit of the CB was fully engrafted, and the grafts from her son still failed to engraft. We conclude that high levels of anti-HLA DQA1/DQB1 DSA could be associated with PGF in our case. Besides DSAs against HLA-A, -B, and -DR, attention should also be paid to DSAs against the HLA-DQ molecule.

Deciphering hematopoietic stem cell heterogeneity: breakthroughs in functional subpopulations and molecular markers

2025-06-18
Yangyang Lei , Mei Guo , Hui‐Sheng Ai | Blood Science

Outcome of second allogeneic hematopoietic cell transplantation in adult patients with relapsed B-cell acute lymphoblastic leukemia in the era of new immunotherapeutic agents

2025-06-17
Daehun Kwag , Jae‐Ho Yoon , Gi June Min +7 more | Bone Marrow Transplantation

Clinical outcomes of offspring and matched unrelated donor transplants in relapsed or refractory severe aplastic anemia patients aged 40–50: a retrospective analysis from the CBMTR over the past decade

2025-06-17
Xin Zhao , Yuping Zhang , Baodong Ye +7 more | Bone Marrow Transplantation

Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients: The Experience of the Grupo Español de Trasplante Hematopoyético y Terapia Celular

2025-06-17
Sara Fernández-Luis , Arancha Bermúdez , Lucrecia Yáñez +7 more | Transplantation
Background. The number of elderly patients who could benefit from an allogeneic hematopoietic stem cell transplantation (allo-HSCT) is continuously increasing; however, the most appropriate way to select elderly candidates for … Background. The number of elderly patients who could benefit from an allogeneic hematopoietic stem cell transplantation (allo-HSCT) is continuously increasing; however, the most appropriate way to select elderly candidates for this procedure is still a matter of debate. Methods. We report the clinical outcomes of a group of 529 patients aged 65 y and older who received a first allo-HSCT between 2011 and 2020 and were reported to the Grupo Español de Trasplante Hematopoyético y Terapia Celular database. Results. The median age was 67.2 y (range, 65–82) and 54 patients (10.2%) were 70 y and older. The 4-y cumulative incidence (CI) of nonrelapse mortality was 32.0% (95% confidence interval [CI], 28-36), CI of relapse was 29.1% (95% CI, 25-33), of overall survival was 43.4% (95% CI, 39-48), of progression-free survival was 38.9% (95% CI, 35-43), and of graft-versus-host disease (GvHD)-free, relapse-free survival was 23.7% (95% CI, 20-28). The 100-d CI of grades II–IV and III–IV acute GvHD was 34.7% (95% CI, 31-39) and 10.4% (95% CI, 8-13), respectively, and the 2-y CI of moderate-severe chronic GvHD was 21.0% (95% CI, 18-25). In the multivariate analysis, a hematopoietic cell transplantation-specific comorbidity index of ≥3 and a high/very high disease risk index were associated with worse overall survival; however, age did not influence the outcomes. Conclusions. Advanced age alone should not serve as an exclusion criterion for allo-HSCT, as the procedure can be both safe and effective in elderly patients with careful candidate selection and optimized transplant strategies.

Is Age No Longer a Barrier to Allogeneic Hematopoietic Stem Cell Transplantation?

2025-06-17
Takanori Teshima | Transplantation

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

2025-06-16
Monzr M. Al Malki , Stephanie Bo‐Subait , Brent R. Logan +7 more | Journal of Clinical Oncology
PURPOSE Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from … PURPOSE Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from underrepresented racial and ethnic groups more frequently rely on HLA-mismatched donors. We hypothesized that post-transplant cyclophosphamide (PTCy) based graft versus host disease (GVHD) prophylaxis would improve outcomes for HSCT recipients using peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors (MMUDs) by reducing the risk of GVHD. METHODS This phase II, nonrandomized, multicenter trial assessed PBSCs in the setting of a GVHD prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil in two adult strata: myeloablative conditioning (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA) conditioning before HSCT from a MMUD. The primary objective was to estimate 1 year overall survival (OS) for each stratum. Key secondary end points included incidences of acute and chronic GVHD. RESULTS A total of 145 patients enrolled, with 59% self-identifying within an underrepresented group. The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD at 6 months were 8% (95% CI, 3.2 to 15.6) for MAC and 10% (95% CI, 4.4 to 18.4) for RIC/NMA. Moderate/severe chronic GVHD at 1 year was 10.3% (95% CI, 4.4 to 18.9) for MAC and 8.6% (95% CI, 3.5 to 16.6) for RIC/NMA. 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS compared with those with donor matched at seven of eight alleles. CONCLUSION PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless of ancestry (ACCESS; ClinicalTrials.gov identifier: NCT04904588 ).

Upadacitinib, a selective <scp>JAK1</scp> inhibitor, for the treatment of steroid refractory chronic graft‐versus‐host disease: A multicentre real‐world study

2025-06-16
Li‐Ting Niu , Minli Hu , Yi Xia +6 more | British Journal of Haematology
Graft-versus-host disease (GVHD) remains an important cause of morbidity and mortality after allo-HSCT. Upadacitinib is a selective JAK1 inhibitor. This study investigated the clinical outcomes of upadacitinib in patients with … Graft-versus-host disease (GVHD) remains an important cause of morbidity and mortality after allo-HSCT. Upadacitinib is a selective JAK1 inhibitor. This study investigated the clinical outcomes of upadacitinib in patients with steroid refractory (SR) chronic graft-versus-host disease (cGVHD). Thirty-two patients with steroid refractory cGVHD (SR-cGVHD) who received upadacitinib treatment were enrolled from three hospitals in China. The overall response rates (ORRs) at 24 weeks and at any time were 81.3% (complete response [CR] rate: 21.9%; partial response [PR] rate: 59.4%) and 84.4% (CR rate: 21.9%; PR rate: 62.5%) respectively. In particular, the cutaneous-specific ORRs at week 24 and at any time were 84.4% (CR rate: 40.6%, PR rate: 43.8%) and 87.6% (CR rate: 43.8%; PR rate: 43.8%) respectively. The rates of infection and haematological toxicity were 18.75% and 6.25%, and two patients (6.25%) experienced grade III adverse events after upadacitinib treatment. One patient died from relapse, and no patient died from non-relapse mortality. The 1-year probabilities of overall survival, failure-free survival and disease-free survival after upadacitinib were 96.6%, 64.9% and 83.1% respectively. In summary, upadacitinib may be an effective and safe treatment for SR-cGVHD.

Outcomes of Haploidentical vs Mismatched Unrelated Donor HCT with Post-Transplant Cyclophosphamide Prophylaxis

2025-06-15
Yosra Aljawai , Jeremy Ramdial , Gabriela Rondón +7 more | Blood Advances
Limited data exist comparing haploidentical and mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease prophylaxis, especially considering donor age. Herein, we report the … Limited data exist comparing haploidentical and mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease prophylaxis, especially considering donor age. Herein, we report the outcomes of 660 haploidentical and 195 MMUD HCT recipients treated at MD Anderson Cancer Center. Beyond standard Cox Proportional Hazards modeling, we employed inverse probability of treatment weighting (IPTW), matched-pair analysis, and performed additional analysis by incorporating an external MMUD validation cohort from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary outcome was overall survival (OS). In multivariable analysis, haploidentical donors had a hazard ratio of 1.20, with a 95% confidence interval (CI), 0.93-1.54, p=.16 compared to the MMUD group. Donor age showed a non-linear association with OS. These findings were corroborated by IPTW, matched-pair analyses, and CIBMTR validation analyses. Exploratory analysis revealed inferior OS for older (&amp;gt;50 years) haploidentical donor group compared to younger (&amp;lt;30 years) MMUD recipients (HR 1.91, 95% CI 1.21-3.01, p=.005). Our analyses suggest that while donor type may play a role, there was a more prominent role for donor age in influencing OS. Moreover, our findings indicate a potential nuance wherein the impact of donor type may vary by donor age. Further research, particularly with larger cohorts, is needed to fully elucidate the complex and potentially interacting roles of donor type and donor age, along with HLA factors.

Good response to oxymetholone in adult aplastic anemia

2025-06-14
Jindaratn Chaipokam , Ponlapat Rojnuckarin | Annals of Hematology
In Thailand, stem cell transplantation and horse antithymocyte globulin (ATG) are not accessible for most adult aplastic anemia (AA) patients. Alternative therapies are required. We conducted a cohort study of … In Thailand, stem cell transplantation and horse antithymocyte globulin (ATG) are not accessible for most adult aplastic anemia (AA) patients. Alternative therapies are required. We conducted a cohort study of 110 adult AA patients treated with oxymetholone alone for at least 30 days from 2013 to 2023. Response at month 6 and prognostic factors were evaluated. The mean age was 63.4 years old and 58.2% were female. Severe and very severe AA (SAA/VSAA) comprised 64.5% and 3.6%, respectively. The initial oxymetholone daily dose was 150 mg in 66.4%. The overall response was 56.4% (50.7% for SAA/VSAA), with a median time to transfusion independence of 11.8 weeks. Deaths were regarded as no response. Seventeen (17.9%) patients discontinued the treatment due to side effects, especially hepatitis (15/17). Androgenic side effects (55.5%) mostly occurred within the first month. Multivariate analysis identified that baseline reticulocyte count > 10 × 109/L (adjusted odds ratio [OR] 7.3, 95% confidence interval [CI] (2.55-21.11), oily skin (OR 4.93, 95%CI 1.50-16.26) and acne (OR 9.78, 95%CI 2.11-45.28) occurring within 2 months were predictive for responses. The SKAR scoring system using these three factors showed an area under the ROC curve of 0.87 (95%CI 0.80-0.92). The 5-year overall survival rate was 77.4%. Poor performance status (p < 0.001) and response status (p < 0.001) significantly impacted mortality. Responding patients demonstrated 94.5% 5-year survival. In conclusion, androgen is a useful treatment option for AA in Thailand. The score based on reticulocytes and androgenic effects could predict the response and potentially help decision-making.

Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin

2025-06-13
David J. Curtis , Sushrut Patil , John Reynolds +7 more | New England Journal of Medicine
Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cancers. The combination of a calcineurin inhibitor … Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cancers. The combination of a calcineurin inhibitor and an antimetabolite remains standard care for graft-versus-host disease (GVHD) prophylaxis in these patients. Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched donor when it is added to or replaces the antimetabolite. However, the effects of post-transplantation cyclophosphamide specifically after SCT from a matched related donor remain uncertain, and effects in the context of myeloablative conditioning are unclear. We randomly assigned adults who were undergoing SCT from a matched related donor after myeloablative or reduced-intensity conditioning to receive either post-transplantation cyclophosphamide-cyclosporin (experimental prophylaxis) or cyclosporin-methotrexate (standard prophylaxis). The primary end point was GVHD-free, relapse-free survival. Among 134 patients who underwent randomization, 66 were assigned to receive experimental prophylaxis and 68 to receive standard prophylaxis. GVHD-free, relapse-free survival was significantly longer with experimental prophylaxis (median, 26.2 months; 95% confidence interval [CI], 9.1 to not reached) than with standard prophylaxis (median, 6.4 months; 95% CI, 5.6 to 8.3; P<0.001 by a log-rank test). GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard prophylaxis (hazard ratio for GVHD, relapse, or death, 0.42; 95% CI, 0.27 to 0.66). The cumulative incidence of grade III to IV acute GVHD at 3 months was 3% (95% CI, 1 to 10) in the experimental-prophylaxis group and 10% (95% CI, 4 to 19) in the standard-prophylaxis group. At 2 years, overall survival was 83% and 71%, respectively (hazard ratio for death, 0.59; 95% CI, 0.29 to 1.19). The incidence of serious adverse events was similar in the two groups in the first 100 days after SCT. The combination of post-transplantation cyclophosphamide and a calcineurin inhibitor led to longer GVHD-free, relapse-free survival than standard prophylaxis after transplantation from a matched related donor with either reduced-intensity or myeloablative conditioning in patients with blood cancers. (Funded by the Australian Government Medical Research Future Fund and others; ALLG BM12 CAST Australian-New Zealand Clinical Trials Registry number, ACTRN12618000505202.).

Correction: Joint models quantify associations between immune cell kinetics and allo-immunological events after allogeneic stem cell transplantation and subsequent donor lymphocyte infusion

2025-06-13
Eva A. S. Koster , Edouard F. Bonneville , Peter A. von dem Borne +7 more | Frontiers in Immunology

Exercise-mobilized donor lymphocyte infusions enhanced with cytokine stimulation for the prevention and treatment of leukemic relapse after allogeneic hematopoietic cell transplantation

2025-06-12
London M. McDougal , Forrest L. Baker , Michael P. Gustafson +2 more | Frontiers in Immunology
Donor lymphocyte infusions (DLI) are a standard therapy following allogeneic hematopoietic cell transplantation (alloHCT) for preventing and treating leukemic relapse in high-risk patients, particularly those with myeloid malignancies such as … Donor lymphocyte infusions (DLI) are a standard therapy following allogeneic hematopoietic cell transplantation (alloHCT) for preventing and treating leukemic relapse in high-risk patients, particularly those with myeloid malignancies such as acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). However, the efficacy of DLI remains suboptimal and is accompanied by a significant risk of life-threatening graft-versus-host disease (GvHD), highlighting the urgent need for strategies that enhance graft-versus-leukemia (GvL) effects while mitigating GvHD. We propose that engaging donors in an acute bout of exercise during peripheral blood lymphocyte collection represents a promising strategy to enhance GvL activity whilst mitigating the risk of GvHD. A single bout of cardiorespiratory exercise triggers catecholamine- and β 2 -adrenergic receptor-dependent mobilization of effector lymphocytes into the bloodstream, significantly increasing the proportion of GvL-promoting NK-cells and γδ T-cells relative to total CD3+ T-cells while reducing GvHD-promoting naïve CD4+ and CD8+ T-cells. Preclinical evidence suggests that these exercise-mobilized lymphocytes infiltrate tumors, exhibit enhanced leukemic control in xenogeneic mice, and display transcriptomic and proteomic profiles indicative of heightened anti-tumor immunity, migration potential and cytokine responsiveness. In this narrative review, we evaluate the advantages and limitations of DLI as a post-alloHCT therapy and propose the novel concept of exercise-enhanced donor lymphocyte infusions (DLI-X) as a simple and cost-effective strategy to augment GvL effects in preventing and treating leukemic relapse. Additionally, we propose that enriching DLI-X with NK-cell-enhancing cytokines (e.g., IL-12, IL-15, and IL-18) will create a novel therapeutic product, termed DLI-XS, with enhanced potency for post-alloHCT applications. We also discuss how DLI-X and DLI-XS, can be leveraged in combination with other post-transplant interventions to maximize GvL effects while minimizing GvHD risks. Finally, we explore the critical role of donor fitness (e.g. V̇O 2 max) in potentially influencing clinical outcomes of alloHCT and post-transplant cell therapies. This comprehensive integration of DLI-X and DLI-XS into existing treatment paradigms represents a promising avenue for enhancing therapeutic outcomes in leukemic relapse post-alloHCT and will underscore the transformative potential of exercise as an accessible and cost-effective adjuvant for DLI.

Real‐World Practice and Challenges of Donor Lymphocyte Apheresis and Infusion: A Single‐Center Experience

2025-06-12
Shuhei Kurosawa , Kyoko Haraguchi , Yuho Najima +7 more | Therapeutic Apheresis and Dialysis
ABSTRACT Background Although donor lymphocyte infusion (DLI) is a treatment option after posttransplant immunomodulation, data on donor lymphocyte apheresis (DLA) remain scarce. Methods We retrospectively analyzed 26 recipients receiving DLI … ABSTRACT Background Although donor lymphocyte infusion (DLI) is a treatment option after posttransplant immunomodulation, data on donor lymphocyte apheresis (DLA) remain scarce. Methods We retrospectively analyzed 26 recipients receiving DLI and their related donors (human leukocyte antigen [HLA]‐matched, n = 9; haploidentical, n = 17). Results The median harvested CD3‐positive cell count (CD3) was 6.71 × 10 7 cells/kg (range, 3.55–19.74). A positive correlation was observed between harvested CD3 and preharvest lymphocyte counts (correlation coefficients = 0.78). In HLA‐matched DLI, the median infused CD3 was 1.19 × 10 7 per cycle and 4.56 × 10 7 cells/kg in total; in haploidentical DLI, 0.25 × 10 7 and 0.44 × 10 7 , respectively. The proportion of total infused CD3 relative to harvested CD3 was 26.3% (range, 1.4–100) in HLA‐matched DLI and 4.5% (range, 1.4–100) in HLA‐haploidentical DLI. Conclusions Our findings reflect real‐world practices and underscore the importance of tailoring DLA to donor and recipient characteristics, particularly in light of the increasing use of haploidentical donors.

A prognostic analysis of patients with acute leukemia and a history of central nervous system involvement undergoing umbilical cord blood transplantation

2025-06-11
Zi-yin Shen , Bingbing Yan , Xinyue Zhang +2 more | Blood Science
To investigate the efficacy and prognosis of umbilical cord blood transplantation (UCBT) in patients with acute leukemia (AL) and a history of central nervous system leukemia (CNSL). We retrospectively evaluated … To investigate the efficacy and prognosis of umbilical cord blood transplantation (UCBT) in patients with acute leukemia (AL) and a history of central nervous system leukemia (CNSL). We retrospectively evaluated 62 patients with AL and a history of CNSL who underwent UCBT at our center between January 2015 and December 2022 (CNSL-positive group). From a concurrent cohort (n = 777) without a history of CNSL, propensity score matching at a 1:2 ratio was conducted based on age, sex, and diagnosis to select 124 matched controls (CNSL-negative group). The results revealed a significantly higher 4-year cumulative incidence of relapse (28.8% vs 16.8%, p = 0.038) and central nervous system (CNS) relapse after UCBT (14.7% vs 3.7%, p = 0.004) in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival (42.0% vs 66.2%, p = 0.004) and overall survival (49.6% vs 69.9%, p = 0.009) rates in the CNSL-positive group were significantly lower than those in the CNSL-negative group. Fine–Gray proportional hazard regression multivariate analysis identified pretransplant CNSL history as an independent high-risk factor for CNS relapse after UCBT (hazard ratio [HR] = 5.710, 95% confidence interval [CI] = 1.737–18.770, p = 0.004). These findings underscore the need to optimize conditioning regimens and graft-vs-host disease prophylaxis and explore novel prophylactic strategies for UCBT to improve long-term survival in patients with AL and a history of CNS involvement.