Biochemistry, Genetics and Molecular Biology › Genetics

Blood disorders and treatments

Works Count: 38244

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This cluster of papers focuses on the genetic basis and clinical manifestations of various neutropenia disorders, including Shwachman-Diamond syndrome, Kostmann disease, and Cohen syndrome. It explores the impact of mutations in genes such as ELANE, HAX1, GFI1, and SBDS on neutrophil development and function, as well as the implications for hematopoietic stem cell transplantation and G-CSF therapy. The research also delves into the molecular mechanisms underlying neutropenia and potential therapeutic targets.

Keywords

Neutropenia; Genetic Mutations; Congenital Disorders; G-CSF Therapy; ELANE Gene; Hematopoietic Stem Cells; Shwachman-Diamond Syndrome; HAX1 Deficiency; Gfi1 Transcription Factor; SBDS Gene

Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia

2000-10-01

David C. Dale , Richard Person , Audrey Anna Bolyard +7 more

Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay

1989-01-01

Kiyoshi Watari , S Asano , Naoki Shirafuji +4 more

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Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia

2001-03-01

Koenraad Devriendt , Annette S. Kim , Gert Mathijs +7 more

LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia

2006-09-07

Julia Skokowa , Gunnar Cario , Murat Uenalan +7 more

Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis

1999-12-01

Marshall S. Horwitz , Kathleen F. Benson , Richard Person +2 more

Neutrophils in Human Diseases

1987-09-10

Harry L. Malech , John I. Gallin

HUMAN neutrophilic polymorphonuclear leukocytes (neutrophils) provide an effective host defense against bacterial and fungal infection, but they are also important in the pathogenesis of tissue damage in certain noninfectious diseases. … HUMAN neutrophilic polymorphonuclear leukocytes (neutrophils) provide an effective host defense against bacterial and fungal infection, but they are also important in the pathogenesis of tissue damage in certain noninfectious diseases. Some important events in neutrophil function that will be discussed in this review are shown in Figure 1.Mild to moderate abnormalities of neutrophil function have been reported in many acquired and congenital diseases.1 2 3 4 5 In most of these disorders, the biochemical or morphologic basis of the defects is unknown and the relevance of the neutrophil defect to the manifestations of the disease is unclear. In contrast, persons with marked neutropenia6 or . . .

Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPα ratio and granulocyte colony-stimulating factor

2003-09-05

Richard Dahl , Jonathan Walsh , D W Lancki +4 more

The neonatal blood count in health and disease.I. Reference values for neutrophilic cells

1979-07-01

Barbara L. Manroe , Arthur G. Weinberg , Charles R. Rosenfeld +1 more

A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients

1997-09-01

H. G. Prentice , Ian Hann , Raoul Herbrecht +7 more

One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 … One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9)/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 0.01) of test-drug-related side-effects, compared to c-AMB. Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 0.01). Analysis was by intention-to-treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 0.5 x 10(9)/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3. A statistically significant difference was found between c-AMB and L-AMB3 (P = 0.03) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms. It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open-label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.

Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2

2003-05-30

Richard Person , Feng-Qian Li , Zhijun Duan +7 more

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Mutations in SBDS are associated with Shwachman–Diamond syndrome

2002-12-23

Graeme R.B. Boocock , Jodi Morrison , M. Popović +4 more

Intrinsic Requirement for Zinc Finger Transcription Factor Gfi-1 in Neutrophil Differentiation

2003-01-01

Hanno Hock , Melanie Hamblen , Heather M. Rooke +4 more

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Effects of Recombinant Human Granulocyte Colony-Stimulating Factor on Neutropenia in Patients with Congenital Agranulocytosis

1989-06-15

Mary Ann Bonilla , AP Gillio , Mary Ruggeiro +7 more

Congenital agranulocytosis is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce … Congenital agranulocytosis is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce the morbidity and mortality associated with this disease, we administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses of 3 to 60 micrograms per kilogram of body weight per day to five patients with congenital agranulocytosis. In all five patients, an increase in the number of neutrophils was noted eight to nine days after the initiation of the effective dosage (the dose at which the neutrophil count reached 1000 cells per microliter or more and the bone marrow showed granulocyte maturation beyond the myelocyte stage). The absolute neutrophil counts rose from less than 100 to between 1300 and 9500 cells per microliter. Marrow aspirates obtained after 14 days at the effective dosage showed maturation to the mature neutrophil stage. The side effects that were observed were medullary pain, splenomegaly, and an elevation of levels of leukocyte alkaline phosphatase. All five patients have had sustained neutrophil counts of 1000 cells per microliter or more for 9 to 13 months while receiving subcutaneous maintenance therapy. Preexisting chronic infections have resolved clinically, and the number of new infectious episodes and the requirement for intravenous antibiotics have decreased. We conclude that treatment with rhG-CSF can lead to a large increase in the numbers of functional neutrophils in patients with congenital agranulocytosis.

INFANTILE GENETIC AGRANULOCYTOSIS

1975-03-01

Rolf Kostmann

ABSTRACT: Kostmann, R. R. O. (Department of Paediatrics, University Hospital, Uppsala, Sweden). Infantile genetic agranulocytosis. Acta Paediatr Stand, 64:362, 1975.–A review of the literature on the subject since 1956 is … ABSTRACT: Kostmann, R. R. O. (Department of Paediatrics, University Hospital, Uppsala, Sweden). Infantile genetic agranulocytosis. Acta Paediatr Stand, 64:362, 1975.–A review of the literature on the subject since 1956 is made in connection with a presentation of ten new cases from northern Sweden. Nine of these are related to the main pedigree published in 1956. Consanguinity between the parents has been established in two of the new families. The clinical course was identical to that described in 1956. A few additional details are presented. The granulocytopenia is present on the first day of life and the granulocyte count subsequently rapidly decreases during the first week. The existence of a diaplacental factor is regarded highly probable. It is assumed that the maturation defect in the granulocyte precursors may be due to deficiency of a serum factor. The fact that many cases of infantile genetic agranulocytosis occur sporadically is finally explained.

Pathophysiology and management of inherited bone marrow failure syndromes

2010-04-26

Akiko Shimamura , Blanche P. Alter

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Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells

2004-09-29

Hanno Hock , Melanie Hamblen , Heather M. Rooke +4 more

A METHOD OF STUDYING LEUKOCYTIC FUNCTIONS IN VIVO

1955-03-01

John W. Rebuck , James H. Crowley

A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction

1979-12-01

Howard A. Pearson , Jeffrey S. Lobel , Samuel A. Kocoshis +5 more

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)

2006-12-24

Christoph Klein , Magda Grudzien , Giridharan Appaswamy +7 more

G-CSF Is an Essential Regulator of Neutrophil Trafficking from the Bone Marrow to the Blood

2002-10-01

Craig L. Semerad , Fulu Liu , Alyssa D. Gregory +2 more

A Syndrome with Congenital Neutropenia and Mutations inG6PC3

2008-12-31

Kaan Boztuğ , Giridharan Appaswamy , Angel Ashikov +7 more

The main features of severe congenital neutropenia are the onset of severe bacterial infections early in life, a paucity of mature neutrophils, and an increased risk of leukemia. In many … The main features of severe congenital neutropenia are the onset of severe bacterial infections early in life, a paucity of mature neutrophils, and an increased risk of leukemia. In many patients, the genetic causes of severe congenital neutropenia are unknown.We performed genomewide genotyping and linkage analysis on two consanguineous pedigrees with a total of five children affected with severe congenital neutropenia. Candidate genes from the linkage interval were sequenced. Functional assays and reconstitution experiments were carried out.All index patients were susceptible to bacterial infections and had very few mature neutrophils in the bone marrow; structural heart defects, urogenital abnormalities, and venous angiectasia on the trunk and extremities were additional features. Linkage analysis of the two index families yielded a combined multipoint lod score of 5.74 on a linkage interval on chromosome 17q21. Sequencing of G6PC3, the candidate gene encoding glucose-6-phosphatase, catalytic subunit 3, revealed a homozygous missense mutation in exon 6 that abolished the enzymatic activity of glucose-6-phosphatase in all affected children in the two families. The patients' neutrophils and fibroblasts had increased susceptibility to apoptosis. The myeloid cells showed evidence of increased endoplasmic reticulum stress and increased activity of glycogen synthase kinase 3beta (GSK-3beta). We identified seven additional, unrelated patients who had severe congenital neutropenia with syndromic features and distinct biallelic mutations in G6PC3.Defective function of glucose-6-phosphatase, catalytic subunit 3, underlies a severe congenital neutropenia syndrome associated with cardiac and urogenital malformations.

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Impaired Production and Increased Apoptosis of Neutrophils in Granulocyte Colony-Stimulating Factor Receptor–Deficient Mice

1996-11-01

Fulu Liu , Huai Yang Wu , Robin L. Wesselschmidt +2 more

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Severe chronic neutropenia: Treatment and follow‐up of patients in the Severe Chronic Neutropenia International Registry

2003-01-28

David C. Dale , Tammy Cottle , Carol Fier +7 more

Abstract Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 × 10 9 /L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia … Abstract Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 × 10 9 /L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia are principal categories of SCN. Since 1994, the Severe Chronic Neutropenia International Registry (SCNIR) has collected data to monitor the clinical course, treatments, and disease outcomes for SCN patients. This report summarizes data for 853 patients, almost all treated with daily or alternate‐day recombinant human granulocyte colony‐stimulating factor (G‐CSF or Filgrastim). G‐CSF treatment increased the ANC overall from 0.34 × 10 9 /L ± 0.018 pre‐treatment to 3.70 × 10 9 /L ± 0.18 during the first year of treatment. For most patients, the responses were durable with patients remaining on the same dose of G‐CSF for many years. Long‐term hematological observations showed stable mean leukocyte and neutrophil counts and gradually increasing hemoglobin levels. Thrombocytopenia developed in 4% of patients. As of January 1, 2000, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G‐CSF treatment. This event occurred without a predictable relationship to the duration or dose of G‐CSF treatment. No patients with cyclic or idiopathic neutropenia developed MDS or AML. Other important adverse events included hepatomegaly, osteoporosis, vasculitis, glomerulonephritis, and deaths in 4 of 14 cases requiring splenectomy. Growth and development and the outcome of pregnancy appeared to be unaffected by G‐CSF treatment. These data indicate that congenital, cyclic, and idiopathic neutropenia can be effectively treated with long‐term G‐CSF. The risk of leukemia, osteoporosis, other potentially adverse events, and pregnancy outcome need to be further evaluated with continuing long‐term observations. Am. J. Hematol. 72:82–93, 2003. © 2003 Wiley‐Liss, Inc.

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Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates.

1987-04-01

Karl Welte , Mary Ann Bonilla , Alfred P. Gillio +6 more

We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in … We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.

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Transcriptional control of granulocyte and monocyte development

2007-10-15

Alan D. Friedman

Epigenetic Regulation of Hematopoietic Differentiation by Gfi-1 and Gfi-1b Is Mediated by the Cofactors CoREST and LSD1

2007-08-01

Shireen Saleque , Jonghwan Kim , Heather M. Rooke +1 more

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WASP: a key immunological multitasker

2010-02-25

Adrian J. Thrasher , Siobhan O. Burns

The Human Rosette-Forming Cell as a Marker of a Population of Thymus-Derived Cells

1972-10-01

Joseph Wybran , Martin C. Carr , H. Hugh Fudenberg

Sheep red blood cells can surround, in vitro, some human peripheral blood lymphocytes in a formation called a rosette. The number of rosetteforming cells (RFC) in 50 normal persons had … Sheep red blood cells can surround, in vitro, some human peripheral blood lymphocytes in a formation called a rosette. The number of rosetteforming cells (RFC) in 50 normal persons had a wide range (4-40%). The organs of 13 human fetuses (11-19 wk conceptional age) were examined for the presence of RFC. The thymus possessed the highest percentage of RFC, the maximum being 65% of total thymocytes in two 15-16 wk fetal specimens. Blood RFC were always present and their number slightly increased in the oldest fetuses. The bone-marrow showed 0-8% in the six fetuses studied. RFC were found in the spleen around the 13th wk and in the liver around the 17th wk of gestation. These observations lead to the hypothesis that human blood RFC may be chiefly thymic derived. Studies of patients with immunological disorders support this hypothesis: one patient with Nezelof syndrome had no blood RFC and four patients with Wiskott-Aldrich syndrome had a low number of blood RFC (1 and 1.5%). Patients with acquired hypogammaglobulinemia showed a normal percentage of RFC. With the fetal thymocytes, the percentage of inhibition with anti-mu serum increased with the fetal age to become complete in the oldest fetuses studied. Incubation of the oldest fetal thymocytes or the blood lymphocytes with anti-gamma serum of anti-mu serum completely inhibited the rosette formation. These results suggest that mu-chain determinants are present on human fetal thymocytes and blood RFC. The significance of the presence of gamma-chain determinants on these cells is unclear.

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Cohen Syndrome Is Caused by Mutations in a Novel Gene, COH1, Encoding a Transmembrane Protein with a Presumed Role in Vesicle-Mediated Sorting and Intracellular Protein Transport

2003-06-01

Juha Kolehmainen , Graeme Black , Anne Saarinen +7 more

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Incipient myelomatosis or «essential« hyperglobulinemia with fibrinogenopenia — a new syndrome?

1944-01-12

Jan Waldenström

Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute Leukemia

1966-02-01

Gerald P. Bodey

Article1 February 1966Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute LeukemiaGERALD P. BODEY, M.D., MONICA BUCKLEY, B.A., Y. S. SATHE, PH.D., EMIL J FREIREICH, M.D.GERALD P. BODEY, … Article1 February 1966Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute LeukemiaGERALD P. BODEY, M.D., MONICA BUCKLEY, B.A., Y. S. SATHE, PH.D., EMIL J FREIREICH, M.D.GERALD P. BODEY, M.D., MONICA BUCKLEY, B.A., Y. S. SATHE, PH.D., EMIL J FREIREICH, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-2-328 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptInfection is currently the major fatal complication of acute leukemia (1). Previous studies have indicated a relationship between leukopenia and the presence of infection in patients with acute leukemia (2-4) and various types of agranulocytosis (5-7). Chemotherapeutic agents with bone marrow toxicity are being used with increasing frequency in malignant and other chronic diseases. Also, a high incidence of infection has accompanied the use of these agents as immunosuppressive therapy in patients receiving organ transplantation (8). The present study examines the quantitative relationships between the presence of infection and the degree and duration of leukopenia in patients with acute leukemia....References1. HERSHBODEYNIESFREIREICH EMGPBAEJ: The causes of death in acute leukemia. A study of 414 patients from 1954-1963. JAMA 193: 105, 1965. CrossrefMedlineGoogle Scholar2. MILLERSHANBROM SPE: Infectious syndromes of leukemias and lymphomas. Amer. J. Med. Sci. 246: 420, 1963. CrossrefMedlineGoogle Scholar3. SILVERBEALSCHNEIDERMANMCCULLOUGH RTGAMANB: The role of the mature neutrophil in bacterial infections in acute leukemia. Blood 12: 814, 1957. CrossrefMedlineGoogle Scholar4. BAKER RD: Leukopenia and therapy in leukemia as factors predisposing to fatal mycoses. Mucormycosis, aspergillosis, and cryptococcosis. Amer. J. Clin. Path. 37: 358, 1962. CrossrefMedlineGoogle Scholar5. BROWNEMARCUS EAAJ: Chronic idiopathic neutropenia. New Eng. J. Med. 262: 795, 1960. CrossrefMedlineGoogle Scholar6. KOSTMANN R: Infantile genetic agranulocytosis. Acta Paediat. (Stockholm) (Supplement 105) 45: 1, 1956. MedlineGoogle Scholar7. SPAETDAMESHEK THW: Chronic hypoplastic neutropenia. Amer. J. Med. 13: 35, 1952. CrossrefMedlineGoogle Scholar8. HILLROLLAROWLANDSRIFKIND JBDTD: Infectious pulmonary disease in patients receiving immunosuppressive therapy for organ transplantation. New Eng. J. Med. 271: 1021, 1964. CrossrefMedlineGoogle Scholar9. FREIKARONLEVINFREIREICHTAYLORHANANIANSELAWRYHOLLANDHOOGSTRATENWOLMANABIRSAWITSKYLEEMILLSBURGERTSPURRPATTERSONEBAUGHJAMESMOON EMRHEJRJJOJFBIJEASSDEOCLRBFGGWJH: Effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. In press. Google Scholar10. LEVINHENDERSONKARONFREIREICH RHEMEJ: Treatment of acute leukemia with methylglyoxal-bis-guanylhydrazone (Methyl GAG). Clin. Pharmacol. Ther. 6: 31, 1965. CrossrefMedlineGoogle Scholar11. RICHARBREAKELL WJES: Evaluation of an electronic particle counter for the counting of white blood cells. Amer. J. Clin. Path. 31: 384, 1959. CrossrefMedlineGoogle Scholar12. BISEL HF: Criteria for the evaluation of response to treatment in acute leukemia. Blood 11: 676, 1956. Google Scholar13. WINTROBE MM: Clinical Hematology, 5th ed. Lea & Febiger, Philadelphia, 1961, p. 254. Google Scholar14. MCFARLANDLEBRE WEP: Abnormal leukocyte response in alcoholism. Ann. Intern. Med. 59: 865, 1963. LinkGoogle Scholar15. BOGGSWINTROBECARTWRIGHT DRMGE: The acute leukemias. Analysis of 322 cases and review of the literature. Medicine (Balt.) 41: 163, 1962. CrossrefMedlineGoogle Scholar16. BOGGSFREI DRE: Clinical studies of fever and infection in cancer. Cancer 13: 1240, 1960. CrossrefGoogle Scholar17. HERSHCARBONEWONGFREIREICH EMPPVGEJ: Inhibition of the primary immune response in man by antimetabolites. Cancer Res. In press. Google Scholar18. JAFFE RH: Morphology of the inflammatory defense reactions in leukemia. Arch. Path. (Chicago) 14: 177, 1932. Google Scholar19. BRAUDEFELTESBROOKS AIJM: Differences between the activities of mature granulocytes in leukemic and normal blood. J. Clin. Invest. 33: 1036, 1954. CrossrefMedlineGoogle Scholar20. BOGGS DR: The cellular composition of inflammatory exudates in human leukemias. Blood 15: 466, 1960. CrossrefMedlineGoogle Scholar21. PERILLIEFINCH PEC: The local exudative cellular response in leukemia. J. Clin. Invest. 39: 1353, 1960. CrossrefMedlineGoogle Scholar22. PERILLIEFINCH PESC: Quantitative studies of the local exudative cellular reaction in acute leukemia. J. Clin. Invest. 43: 425, 1964. CrossrefMedlineGoogle Scholar23. PAGEGOOD ARRA: A clinical and experimental study of the function of neutrophils in the inflammatory response. Amer. J. Path. 34: 645, 1958. MedlineGoogle Scholar24. RAABHOEPRICHWINTROBECARTWRIGHT SOPDMMGE: The clinical significance of fever in acute leukemia. Blood 16: 1609, 1960. CrossrefMedlineGoogle Scholar25. MILLER CP: The effect of irradiation on natural resistance to infection. Ann. N. Y. Acad. Sci. 66: 280, 1956. CrossrefGoogle Scholar26. DERBYROGERS BMDE: Studies on bacteremia. V. The effect of simultaneous leukopenia and reticuloendothelial blockade on the early blood stream clearance of staphylococci and Escherichia coli. J. Exp. Med. 113: 1053, 1961. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, MarylandFrom the Medicine Branch, Leukemia Service, and the Mathematical and Statistics and Applied Mathematical Section, National Cancer Institute, National Institutes of Health, Bethesda, Md.Requests for reprints should be addressed to Gerald P. Bodey, M.D., Building 10, Room 2B45, National Institutes of Health, Bethesda, Md. 20014. 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and supportive modality requirements in critically ill cancer patientsAssessing Needs and Experiences of Preparing for Medical Emergencies Among Children With Cancer and Their CaregiversPossibilities of supportive therapy in patients with blood system tumors and malignant neoplasmsHigh Burden of Serious Bacterial Infections in African Children Treated for CancerEfficacy and safety of granulocyte transfusion in children: A single‐center experienceEvaluation of a 0.75 × 10 9 /L absolute neutrophil count cut‐off for antimicrobial prophylaxis in canine cancer chemotherapy patientsInfectious disease considerations in immunocompromised patientsRectal colonization with multidrug-resistant gram-negative bacteria in patients with hematological malignancies: a prospective studyThe Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile NeutropeniaAn in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopeniasPersonalized cancer supportive care in COVID-19 eraAssociation Between Depth of Neutropenia and Clinical Outcomes in Febrile Pediatric Cancer and/or Patients Undergoing Hematopoietic Stem-cell TransplantationPrediction of Survival Benefit of Filgrastim in Adult and Pediatric Patients With Acute Radiation SyndromeEvaluation of the HemoCue WBC DIFF in leukopenic patient samplesAge‐related prevalence and clinical significance of neutropenia ‐ isolated or combined with other cytopenias: Real world data from 373 820 primary care individualsInterventions aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN), a systematic reviewPreoperative Nutritional Status Contributes to the Development of Neutropenia Event in Patients With Gastric Cancer Receiving CAPEOX Adjuvant ChemotherapyThe cost of a “benign” condition: Healthcare utilization and infectious outcomes in young children with primary autoimmune neutropeniaComparison of two different anti-infectious approaches after high-dose chemotherapy and autologous stem cell transplantation for hematologic malignancies in a 12-year period in British Hospital, UruguayIn canine bacterial pneumonia circulating granulocyte counts determine outcome from donor cellsD-Index–Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority TrialProphylaxis of febrile neutropenia with colony-stimulating factors: the first 25 yearsNeutropenia management in patients receiving myelosuppressive polychemotherapy for early breast cancer in Belgium: BRONS study resultsTranscriptional regulation of neutrophil differentiation and function during inflammationAssociation of time to antibiotics and clinical outcomes in patients with fever and neutropenia during chemotherapy for cancer: a systematic reviewUp-to-Date Infection Control Practices for Febrile Neutropenic PatientsRecent advances and future directions in the management of the immunocompromised hostThe Role of Neutrophils in the Immune System: An OverviewEfficient Bayesian Expert Models for Fever in Neutropenia and Fever in Neutropenia with BacteremiaAntimicrobial Prophylaxis in High-Risk Oncology PatientsInfection in the Patient With Cancer Detection and Control of Biofilm Formation by Staphylococcus aureus from Febrile Neutropenic Patient Protocol for a systematic review of time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN) and interventions aiming to reduce TTAEffect of adjunctive corticosteroid on 28-day mortality in neutropenic patients with septic shockImpact of neutropenia on central venous catheter–related bloodstream infections in patients with hematological malignancies at the time of central venous catheter insertion: A matched-pair analysisPeritoneal GATA6+ macrophages function as a portal for Staphylococcus aureus disseminationPhysical Exercise during Radiation and ChemotherapyImpact of preleukemic mutations and their persistence on hematologic recovery after induction chemotherapy for AMLThe clinical management of invasive mold infection in children with cancer or undergoing hematopoietic stem cell transplantationInpatient Health Care Utilization in Children With Hemophilia Before and After the Joint Outcome Study PublicationUse of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health EmergencyUse of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health EmergencyNonneutropenic fever in children with cancer: A scoping review of management and outcomeHost and Graft Factors Impacting Infection Risk in Hematopoietic Cell TransplantationWork-up for Fever During Neutropenia for Both the Stem Cell Transplant Recipient and the Hematologic Malignancy PatientInappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug ResistanceOutpatient treatment for people with cancer who develop a low-risk febrile neutropaenic eventRisk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropeniaCan immune biomarkers predict infections in solid organ transplant recipients? A review of current evidenceManagement of Patients With Fever and Neutropenia Through the Arc of Time A Narrative ReviewPhilip A. Pizzo, MDSTUDY ON HAEMATOLOGICAL PROFILE AMONG HIV POSITIVE PATIENTSThe immune response to fungal challengeNeutrophil Heterogeneity as Therapeutic Opportunity in Immune-Mediated DiseaseSpecific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8+ T Cell ResponsesEpisodes of fever in neutropenia in pediatric patients with cancer in Bern, Switzerland, 1993–2012Prospective Evaluation of Multinational Association of Supportive Care in Cancer Risk Index Score for Gynecologic Oncology Patients With Febrile NeutropeniaAIDS-Related Kaposi Sarcoma, Version 2.2019Infections in Allogeneic Stem Cell TransplantationRespiratory Tract Infections: Sinusitis, Bronchitis, and PneumoniaOral Considerations for the Head and Neck Cancer PatientAntimicrobial Prophylaxis in High-Risk Oncology PatientsAntimicrobial Prophylaxis in High-Risk Oncology PatientsNeutropenic SepsisHematopoietic Growth Factors in the Management of Anemia and Febrile NeutropeniaCreation and evaluation of a cancer chemotherapy order review guide for use at a community hospitalOptimal Management of Neutropenic Fever in Patients With CancerFebrile Neutropenia: An Ounce of Prevention or a Pound of CureEffectiveness of filgrastim and polyethylene glycol-filgrastim in the treatment of postchemotherapy neutropenia in children: Phase I clinical trialPediatric patients at risk for fever in chemotherapy-induced neutropenia in Bern, Switzerland, 1993-2012One-year mortality and Periprosthetic infection rates after Total knee Arthroplasty in Cancer patients: a population-based cohort studyClinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapyCost-effectiveness analysis of lipegfilgrastim as primary prophylaxis in women with breast cancer in Australia: a modelled economic evaluationThe Lung Microvasculature Is a Functional Immune NicheLeukopenia and lack of ribavirin predict poor outcomes in patients with haematological malignancies and respiratory syncytial virus infectionInfectious complications in patients with acute leukemia according to the duration of neutropeniaAntimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline UpdateExtended vs Bolus Infusion of Broad-Spectrum β-Lactams for Febrile Neutropenia: An Unblinded, Randomized TrialAssociations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemiaA cohort study on protocol-based nurse-led out-patient management of post-chemotherapy low-risk febrile neutropeniaPulmonary Infections in Immunocompromised HostsAntibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendationsPrescribing Empiric Antibiotics for Febrile Neutropenia: Compliance with Institutional Febrile Neutropenia GuidelinesCharacteristics and Clinical Outcomes of Critically Ill Cancer Patients Admitted to Korean Intensive Care UnitsTissue macrophages as mediators of a healthy relationship with gut commensal microbiotaDrug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant PhysiciansThe Infectious and Noninfectious Etiology, Clinical Picture and Outcome of Neutropenia in Immunocompetent Hospitalized ChildrenFully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to G AlertPredictors of chemoradiation related febrile neutropenia prophylaxis in older adults – Experience from a limited resource settingReduced Neutrophil Elastase Activity and Neutrophil Extracellular Traps in Pediatric Acute Myeloid Leukemia May Increase the Rate of InfectionsNeutropenia in pediatric heart transplant recipientsClinicohematological profile of febrile neutropenia in childhood acute leukemia and utility of serum procalcitonin levels in neutropenic patientsHost Control of Fungal Infections: Lessons from Basic Studies and Human CohortsNatural killer cells as a therapeutic tool for infectious diseases - current status and future perspectivesThe enigmatic neutrophil: what we do not knowRadionuclide Imaging of Infection and Inflammation in Children: a ReviewRethinking Antimicrobial Prophylaxis in the Transplant Patient in the World of Emerging Resistant Organisms—Where Are We Today?Granulocyte transfusions in the management of neutropenic fever: A pediatric perspectiveSEIFEM 2017: from real life to an agreement on the use of granulocyte transfusions and colony-stimulating factors for prophylaxis and treatment of infectious complications in patients with hematologic malignant disordersA randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patientsNeutropenic SepsisSupportive Care for Patients with Leukemia: A Historical PerspectiveInfections in CancerInfections and CancerFever and GranulocytopeniaOncologic EmergenciesManagement and cost analysis of cancer patients treated with G-CSF: a cohort study based on the French national healthcare insurance databaseImpact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: An overview about well-established and recently emerging clinical dataNeutropenic FeverMultidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa , and vancomycin-resistant Enterococcus : Three major threats to hematopoietic stem cell transplant recipientsHealthcare utilization and spending by children with cancer on MedicaidRisk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotypePotential for Monitoring Gut Microbiota for Diagnosing Infections and Graft-versus-Host Disease in Cancer and Stem Cell Transplant PatientsMyelosuppression, Bone Disease, and Acute Renal Failure: Evidence-Based Recommendations for Oncologic EmergenciesCost-Utility Analysis of Lipegfilgrastim Compared to Pegfilgrastim for the Prophylaxis of Chemotherapy-Induced Neutropenia in Patients with Stage II-IV Breast CancerDefining a therapeutic window for kinase inhibitors in leukemia to avoid neutropeniaThe effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic reviewA demonstration of analytical similarity comparing a proposed biosimilar pegfilgrastim and reference pegfilgrastimCuantificación de citoquinas y su relación con la presencia de bacteriemia en leucemias agudas y neutropenia febril postquimioterapiaMonocyte nadir is a possible indicator for neutrophil nadir during lung cancer chemotherapyHarnessing Neutrophil Survival Mechanisms during Chronic Infection by Pseudomonas aeruginosa: Novel Therapeutic Targets to Dampen Inflammation in Cystic FibrosisEpic Immune Battles of History: Neutrophils vs. Staphylococcus aureusTherapeutic Use of Filgrastim for Established Febrile Neutropenia Is Cost Effective Among Patients With Solid Tumors and LymphomasIndwelling Pleural Catheters for Patients with Hematologic Malignancies. A 14-Year, Single-Center ExperienceRisk factors and impact of Clostridium difficile recurrence on haematology patientsGranulocyte transfusions in the management of invasive fungal infectionsThe lung is a host defense niche for immediate neutrophil-mediated vascular protectionProphylactic Measures During Induction for Acute Myeloid LeukemiaHematologic Complications and Blood Bank SupportOncologic EmergenciesSKIN, OROPHARYNGEAL AND RESPIRATORY TRACT INFECTIONS IN PATIENTS WITH ACUTE LEUKAEMIA RECEIVING CHEMOTHERAPYIs parenteral chemotherapy safe in rural hospitals? A prospective audit of neutropenic fever in Albany Hospital, a regional West Australian cancer centreCLINICAL PROFILE AND OUTCOME OF FEBRILE NEUTROPENIC CANCER PATIENTS IN A TERTIARY CARE CENTREImmunotherapy of Invasive Fungal DiseaseNeutropeniaInfections in the Cancer PatientProperdin Levels in Individuals with Chemotherapy-Induced NeutropeniaRelease of Danger-Associated Molecular Patterns following Chemotherapy Does Not Induce Immunoparalysis in Leukemia PatientsApplying Multinational Association of Supportive Care of Cancer Index Score for Identifying Febrile Neutropenia Patients at High Risk of Complications at Tertiary Care Hospital, PakistanPost-liver transplant myeloid maturation arrestThe Emergency Care of Patients With Cancer: Setting the Research AgendaEvaluation of Mannose-Binding Lectin is a Useful Approach to Predict the Risk of Infectious Complications Following Autologous Hematopoietic Stem Cell TransplantationClinical relevance of molecular identification of microorganisms and detection of antimicrobial resistance genes in bloodstream infections of paediatric cancer patientsCFTR targeting during activation of human neutrophilsOutcome of severe infections in afebrile neutropenic cancer patientsStaphylococcus aureus : the current state of disease, pathophysiology and strategies for preventionDrug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patientsShorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology GroupAnalysis of overall survival in a large multiethnic cohort reveals absolute neutrophil count of 1,100 as a novel prognostic cutoff in African AmericansExogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapyGranulocyte transfusions in critically ill children with prolonged neutropenia: side effects and survival rates from a single-center analysisRelationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignanciesClinical prognostic factors for time to positivity in cancer patients with bloodstream infectionsStaphylococcus aureus Pathogenesis and Virulence Factor RegulationChemotherapy-induced neutropenia among pediatric cancer patients in Egypt: Risks and consequencesOverview of Infections in the Immunocompromised HostTherapeutic Potential of Polyphenols from Epilobium Angustifolium (Fireweed)A randomized, double‐blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE (R) chemotherapy for malignant lymphomaA clinical evaluation of efficacy and safety of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia in a tertiary care centre of north IndiaPreoperative chemotherapy and corticosteroids: independent predictors of cranial surgical-site infectionsIncreased use of antimicrobial medication in bulimia nervosa and binge-eating disorder prior to the eating disorder treatmentClinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factorPrédiction de la gravité des neutropénies fébriles par le score de MASCC : une étude de cohorte rétrospectiveNeutrophil left shift and white blood cell count as markers of bacterial infectionPrevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal studyPreventing Infections in Children with CancerCharacteristics of Children With Cancer Discharged or Admitted From the Emergency DepartmentFrequent Emergency Department Utilizers Among Children with CancerOverview of Infections in the Immunocompromised HostEmerging agents for the prevention of treatment induced neutropenia in adult cancer patientsTrajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapyA Randomized Multicenter Phase III Study of Single Administration of Mecapegfilgrastim (HHPG-19K), a Pegfilgrastim Biosimilar, for Prophylaxis of Chemotherapy-Induced Neutropenia in Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC)A Validated Method for Identifying Unplanned Pediatric ReadmissionVery early discharge versus early discharge versus non-early discharge in children with ca

Prevalence of Neutropenia in the U.S. Population: Age, Sex, Smoking Status, and Ethnic Differences

2007-04-03

Matthew M. Hsieh , James E. Everhart , Danita D. Byrd-Holt +2 more

Background: Benign reductions in neutrophil counts may be more common at certain ages and in certain ethnic groups and may be affected by sex and smoking status. Objective: To determine … Background: Benign reductions in neutrophil counts may be more common at certain ages and in certain ethnic groups and may be affected by sex and smoking status. Objective: To determine differences in neutrophil counts in the U.S. population according to ethnicity, age, sex, and smoking status. Design: Population-based, cross-sectional study. Setting: Various locations in the United States. Participants: 25 222 participants in the 1999 to 2004 National Health and Nutrition Examination Survey who were 1 year of age or older. Measurements: Complete blood counts and comparison of means and the proportion of participants with neutropenia. Results: Relative to white participants, black participants had lower leukocyte counts (mean difference, 0.89 × 109 cells/L; P < 0.001), lower neutrophil counts (0.83 × 109 cells/L; P < 0.001), and similar lymphocyte counts (0.022 × 109 cells/L; P = 0.36), whereas Mexican-American participants had slightly higher mean leukocyte counts (0.16 × 109 cells/L; P = 0.014), higher neutrophil counts (0.11 × 109 cells/L; P = 0.026), and higher lymphocyte counts (0.095 × 109 cells/L; P < 0.001). The prevalence of neutropenia (neutrophil count <1.5 × 109 cells/L) was 4.5% among black participants, 0.79% among white participants, and 0.38% among Mexican-American participants. The prevalence of neutropenia was higher among males and children younger than 5 years of age. Neutrophil counts less than 1.0 × 109 cells/L were observed in fewer than 1% of the overall sample (0.57% in black participants, 0.11% in white participants, and 0.08% in Mexican-American participants). Smoking was associated with higher leukocyte and neutrophil counts but had a smaller effect among black and Mexican-American participants than among white participants. Limitation: Because estimates are based on single measures, fluctuations over time could not be determined. Conclusions: In the United States, neutrophil counts are lower in black persons than in white persons and neutropenia is more prevalent in black persons. Neutrophil counts are slightly higher in Mexican-American persons than in white persons, and neutropenia is uncommon in both groups. The clinical implications of these findings are unclear, but they suggest that when determining the need for a diagnostic evaluation for neutropenia, clinicians should consider the patient's age, sex, ethnicity, and smoking status.

Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H).

1990-06-01

H. Patrick McNeil , Richard J. Simpson , C.N. Chesterman +1 more

Anti-phospholipid (aPL) antibodies that exhibit binding in cardiolipin (CL) ELISA can be purified to greater than 95% purity by sequential phospholipid affinity and ion-exchange chromatography. However, these highly purified aPL … Anti-phospholipid (aPL) antibodies that exhibit binding in cardiolipin (CL) ELISA can be purified to greater than 95% purity by sequential phospholipid affinity and ion-exchange chromatography. However, these highly purified aPL antibodies do not bind to the CL antigen when assayed by a modified CL ELISA in which the blocking agent does not contain bovine serum, nor do they bind to phospholipid affinity columns. Binding to the phospholipid antigen will only occur if normal human plasma, human serum, or bovine serum is present, suggesting that the binding of aPL antibodies to CL requires the presence of a plasma/serum cofactor. Using sequential phospholipid affinity, gel-filtration, and ion-exchange chromatography, we have purified this cofactor to homogeneity and shown that the binding of aPL antibodies to CL requires the presence of this cofactor in a dose-dependent manner. N-terminal region sequence analysis of the molecule has identified the cofactor as beta 2-glycoprotein I (beta 2GPI) (apolipoprotein H), a plasma protein known to bind to anionic phospholipids. These findings indicate that the presence of beta 2GPI is an absolute requirement for antibody-phospholipid interaction, suggesting that bound beta 2GPI forms the antigen to which aPL antibodies are directed. Recent evidence indicates that beta 2GPI exerts multiple inhibitory effects on the coagulation pathway and platelet aggregation. Interference with the function of beta 2GPI by aPL antibodies could explain the thrombotic diathesis seen in association with these antibodies.

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Autoimmunity in Wiskott-Aldrich Syndrome: Risk Factors, Clinical Features, and Outcome in a Single-Center Cohort of 55 Patients

2003-05-01

Sophie Dupuis‐Girod , Jacques Médioni , Élie Haddad +7 more

To evaluate the occurrence of autoimmune and inflammatory complications in Wiskott-Aldrich syndrome (WAS) and to determine risk factors and the prognosis of such complications with the aim of improving the … To evaluate the occurrence of autoimmune and inflammatory complications in Wiskott-Aldrich syndrome (WAS) and to determine risk factors and the prognosis of such complications with the aim of improving the definition of treatment options.We reviewed the records of 55 patients with WAS evaluated at Necker-Enfants Malades Hospital (Paris) from 1980 to 2000.Forty patients (72%) had at least 1 autoimmune or inflammatory complication. Autoimmune hemolytic anemia was detected in 20 cases (36%); in all cases, onset occurred before the age of 5 years. Other complications included neutropenia (25%), arthritis (29%), skin vasculitis (22%), cerebral vasculitis (7%), inflammatory bowel disease (9%), and renal disease (3%). The median survival of the entire population was 14.5 years. Two autoimmune complications and 1 biological factor were predictive of a poor prognosis in this population: autoimmune hemolytic anemia, severe thrombocytopenia recurring after splenectomy, and high serum immunoglobulin M (IgM) levels before splenectomy. Autoimmune hemolytic anemia was significantly more observed in patients with high serum IgM level.High serum IgM concentration before splenectomy was identified as a risk factor for autoimmune hemolytic anemia; however, it must be confirmed. Autoimmune hemolytic anemia and severe thrombocytopenia recurring after splenectomy were 2 indicators of a poor prognosis. Those results suggest that patients with WAS and IgM levels more than mean + 2 standard deviations before splenectomy should be placed under strict surveillance. Furthermore, severe autoimmune complications should lead, as early as possible, to hematopoietic stem cell transplantation using the best available donor.

Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle.

1991-11-01

Page A.W. Anderson , Nadia N. Malouf , Annette E. Oakeley +2 more

The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between … The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between normal and failing myocardium led us to examine the ontogenic expression of TnT in human striated muscle. Left ventricular samples were obtained from patients with severe heart failure undergoing cardiac transplantation and normal adult organ donors. Fetal muscle was obtained from aborted fetuses after 14-15 weeks of gestation, and adult skeletal muscle was obtained from surgical biopsies. Western blots of normal and failing adult heart proteins demonstrated that two isoforms, TnT1 and TnT2, are expressed in different amounts, with TnT2 being significantly greater in failing hearts (p less than 0.004). Western blots of two-dimensional gels of these proteins resolved two predominant spots of both TnT1 and TnT2 and several minor TnT species. Alkaline phosphatase treatment converted the two major spots of each isoform into the single more basic spots. A comparison of the ATPase activities and the TnT2 percentage of total TnT in individual failing and normal adult hearts demonstrated an inverse and negative relation (r = 0.7, p less than 0.02). In the fetal heart, four TnT isoforms were found, two of which had the same electrophoretic mobilities as the adult cardiac isoforms TnT1 and TnT2. Fetal skeletal muscle expressed two of the four fetal cardiac TnT isoforms, one of which comigrated with adult cardiac TnT1. These cardiac isoforms were expressed in low abundance in fetal skeletal muscle relative to seven fast skeletal muscle TnT isoforms. No cardiac isoforms were present in adult skeletal muscle. Because many etiologies caused heart failure in the transplant patients, we propose that the disease-associated increased expression of the TnT isoform TnT2 is an adaptation to the heart failure state and a partial recapitulation of the fetal expression of cardiac TnT isoforms.

Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases

2010-11-15

Brice Korkmaz , Marshall S. Horwitz , Dieter E. Jenne +1 more

Polymorphonuclear neutrophils are the first cells recruited to inflammatory sites and form the earliest line of defense against invading microorganisms. Neutrophil elastase, proteinase 3, and cathepsin G are three hematopoietic … Polymorphonuclear neutrophils are the first cells recruited to inflammatory sites and form the earliest line of defense against invading microorganisms. Neutrophil elastase, proteinase 3, and cathepsin G are three hematopoietic serine proteases stored in large quantities in neutrophil cytoplasmic azurophilic granules. They act in combination with reactive oxygen species to help degrade engulfed microorganisms inside phagolysosomes. These proteases are also externalized in an active form during neutrophil activation at inflammatory sites, thus contributing to the regulation of inflammatory and immune responses. As multifunctional proteases, they also play a regulatory role in noninfectious inflammatory diseases. Mutations in the ELA2/ELANE gene, encoding neutrophil elastase, are the cause of human congenital neutropenia. Neutrophil membrane-bound proteinase 3 serves as an autoantigen in Wegener granulomatosis, a systemic autoimmune vasculitis. All three proteases are affected by mutations of the gene (CTSC) encoding dipeptidyl peptidase I, a protease required for activation of their proform before storage in cytoplasmic granules. Mutations of CTSC cause Papillon-Lefèvre syndrome. Because of their roles in host defense and disease, elastase, proteinase 3, and cathepsin G are of interest as potential therapeutic targets. In this review, we describe the physicochemical functions of these proteases, toward a goal of better delineating their role in human diseases and identifying new therapeutic strategies based on the modulation of their bioavailability and activity. We also describe how nonhuman primate experimental models could assist with testing the efficacy of proposed therapeutic strategies.

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Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury

2009-03-22

Andrés Hidalgo , Jungshan Chang , Jung-Eun Jang +3 more

The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy

2006-02-24

Philip S. Rosenberg

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Systematic Review: Agranulocytosis Induced by Nonchemotherapy Drugs

2007-05-01

Frank Andersohn , Christine Konzen , Edeltraut Garbe

Background: Nonchemotherapy drug–induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 × 109 cells/L due to immunologic or … Background: Nonchemotherapy drug–induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 × 109 cells/L due to immunologic or cytotoxic mechanisms. Purpose: To systematically review case reports of drugs that are definitely or probably related to agranulocytosis. Data Sources: English-language and German-language reports in MEDLINE (1966 to 2006) or EMBASE (1989 to 2006) and in bibliographies of retrieved articles. Study Selection: Published case reports of patients with nonchemotherapy drug–induced agranulocytosis. Data Extraction: One reviewer abstracted details about cases and assessed causality between drug intake and agranulocytosis by using World Health Organization assessment criteria. Data Synthesis: Causality assessments of 980 reported cases of agranulocytosis were definite in 56 (6%), probable in 436 (44%), possible in 481 (49%), and unlikely in 7 (1%). A total of 125 drugs were definitely or probably related to agranulocytosis. Drugs for which more than 10 reports were available (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine) accounted for more than 50% of definite or probable reports. Proportions of fatal cases decreased between 1966 and 2006. More patients with a neutrophil count nadir less than 0.1 × 109 cells/L had fatal complications than did those with a neutrophil count nadir of 0.1 × 109 cells/L or greater (10% vs. 3%; P < 0.001). Patients treated with hematopoietic growth factors had a shorter median duration of neutropenia (8 days vs. 9 days; P = 0.015) and, among asymptomatic patients at diagnosis, had a lower proportion of infectious or fatal complications (14% vs. 29%; P = 0.030) than patients without such treatment. Limitations: Case reports cannot provide rates of drug-induced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes. Conclusions: Many drugs can cause nonchemotherapy drug–induced agranulocytosis. Case fatality may be decreasing over time with the availability of better treatment.

Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia

2010-03-21

Marc H.G.P. Raaijmakers , Siddhartha Mukherjee , Shangqin Guo +7 more

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LEUKOCYTE ADHESION DEFICIENCY: An Inherited Defect in the Mac-1, LFA-1, and p150,95 Glycoproteins

1987-02-01

D. C. Anderson , Timothy A. Springer

Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions … Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells. Features of this disease are attributable to deficiency (or absence) of cell surface expression of a family of functionally and structurally related glycoproteins. These include Mac-1 (complement receptor type 3), lymphocyte function-associated antigen-1 (LFA-1), and p150,95. Defective biosynthesis of the beta chain shared by each molecule (comprised of alpha 1 beta 1 complexes) represents the fundamental molecular basis of this disease. Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.

Effect of Recombinant Human Granulocyte–Macrophage Colony-Stimulating Factor on Myelopoiesis in the Acquired Immunodeficiency Syndrome

1987-09-03

Jerome E. Groopman , Ronald T. Mitsuyasu , Michael DeLeo +2 more

We administered recombinant (biosynthetic) human granulocyte-macrophage colony-stimulating factor (GM-CSF) to 16 patients with the acquired immunodeficiency syndrome (AIDS) and leukopenia (2225 +/- 614 cells per microliter [mean +/- SD]). Each … We administered recombinant (biosynthetic) human granulocyte-macrophage colony-stimulating factor (GM-CSF) to 16 patients with the acquired immunodeficiency syndrome (AIDS) and leukopenia (2225 +/- 614 cells per microliter [mean +/- SD]). Each patient first received a single intravenous dose; 48 hours later a 14-day continuous intravenous infusion of the agent was begun. The doses used were 1.3 X 10(3) (n = 4), 2.6 X 10(3) (n = 4), 5.2 X 10(3) (n = 4), 1.0 X 10(4) (n = 3), or 2.0 X 10(4) (n = 1) U per kilogram of body weight per day. Administration of recombinant GM-CSF resulted in dose-dependent increases in circulating leukocytes and in increases in circulating neutrophils, eosinophils, and monocytes. The peak leukocyte count ranged from 4575 +/- 2397 cells per microliter at the lowest dose, to 48,700 in the patient receiving the highest dose. Mild side effects--low-grade fever, myalgia, phlebitis, and flushing--were observed in some patients; there were no life-threatening toxic reactions. Our data demonstrate that recombinant human GM-CSF is well tolerated and biologically active in leukopenic patients with AIDS. Strategies to increase the number and function of circulating leukocytes may reduce the morbidity and mortality of infections in these and other patients with leukopenia.

Inhibition of Granulocyte Adherence by Ethanol, Prednisone, and Aspirin, Measured with an Assay System

1974-09-26

Rob Roy MacGregor , Phillip J. Spagnuolo , Arnold Lentnek

A simple, rapid, in vitro assay was developed to study granulocyte adherence, an important component of the inflammatory reaction. Heparinized whole blood is filtered through nylon fiber packed in Pasteur … A simple, rapid, in vitro assay was developed to study granulocyte adherence, an important component of the inflammatory reaction. Heparinized whole blood is filtered through nylon fiber packed in Pasteur pipettes, and the percentage of granulocytes adhering is calculated. Test variability from morning to evening, before and after meals, and on successive days is less than 10 per cent. In vitro exposure of whole blood to ethanol concentrations varying from 100 to 1000 mg per 100 ml caused a dose-dependent, significant inhibition of adherence (16–87 per cent, p<0.05), but incubation with sodium salicylate (5 to 50 mg per 100 ml) or hydrocortisone sodium succinate (500 to 3000 μg per 100 ml) had no effect. In all volunteers receiving 40 mg of prednisone or 1.2 g of aspirin, impaired adherence developed, suggesting that glucocorticoids and salicylates may affect adherence in vivo by inducing an inhibitor. The anti-inflammatory effect of salicylates, hydrocortisone and ethanol may be secondary to their inhibition of granulocyte adherence. (N Engl J Med 291:642–646, 1974)

Treatment of Cyclic Neutropenia with Granulocyte Colony-Stimulating Factor

1989-05-18

William P. Hammond , Thomas H. Price , L M Souza +1 more

Six patients with cyclic neutropenia were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months. All had a history of recurrent aphthous stomatitis, pharyngitis, lymphadenopathy, fever, … Six patients with cyclic neutropenia were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months. All had a history of recurrent aphthous stomatitis, pharyngitis, lymphadenopathy, fever, and numerous infections during periods of neutropenia. Serial blood-cell counts, findings on bone marrow examination, and signs and symptoms were evaluated before and during the daily administration of G-CSF (3 to 10 μg kilogram of body weight per day), either intravenously or subcutaneously. The kinetics of labeled autologous blood neutrophils and the migration of neutrophils to skin chambers were also measured. Recombinant human G-CSF increased the mean (±SEM) neutrophil counts from 717±171 per microliter to 9814±2198 per microliter (P = 0.009). In five of the six patients, the cycling of blood-cell counts continued, but the length of the period decreased from 21 to 14 days. The number of days of severe neutropenia was reduced (P = 0.002). Neutrophil turnover increased almost four-fold (P = 0.005), whereas neutrophil migration to a skin chamber was normal. G-CSF therapy reduced the frequency of oropharyngeal inflammation, fever, and infections in these patients. During the first 40 months of treatment, no typical mouth ulcers or bacterial infections occurred; recurrent gingivitis improved. We conclude that G-CSF is effective for the treatment of cyclic neutropenia in humans. (N Engl J Med 1989; 320:1306–11.)

Mutations in the Gene for the Granulocyte Colony-Stimulating–Factor Receptor in Patients with Acute Myeloid Leukemia Preceded by Severe Congenital Neutropenia

1995-08-24

Fan Dong , Russell K. Brynes , Nicola Tidow +3 more

In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the … In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction pathways for granulocyte colony-stimulating factor (G-CSF) may play a part in the progression to acute myeloid leukemia.

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Letter: A method for assaying von Willebrand factor (ristocetin cofactor).

1975-09-30

Donald E. Macfarlane , Jeanne Stibbe , Edward P. Kirby +3 more

Isolation of mononuclear cells and granulocytes from human blood.

1968-01-01

Arne Bøyum

PENICILLIN AND STREPTOMYCIN

1947-09-01

A. F. Fleming , E. B. Chain

A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia

1993-05-15

DC Dale , MA Bonilla , MW Davis +7 more

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Diagnosis and Clinical Course of Autoimmune Neutropenia in Infancy: Analysis of 240 Cases

1998-01-01

Juergen Bux , Georg M. N. Behrens , Gudrun Jaeger +1 more

Adult presentation of Shwachman-Diamond syndrome complicated by liver cirrhosis and pancreatic fat infiltration: A case report

2025-06-25

Haijun Guo | World Journal of Hepatology

BACKGROUND Shwachman-Diamond syndrome (SDS) is a rare genetic disorder that affects multiple organs, primarily the liver. Most patients are diagnosed during infancy or early childhood. As they grow older, the … BACKGROUND Shwachman-Diamond syndrome (SDS) is a rare genetic disorder that affects multiple organs, primarily the liver. Most patients are diagnosed during infancy or early childhood. As they grow older, the majority of affected children may experience spontaneous remission, and cases of cirrhosis in adults are rarely reported. CASE SUMMARY A 36-year-old male patient presented with massive ascites. Laboratory tests revealed pancytopenia and a serum-ascites albumin gradient greater than 1.1 g/dL. An abdominal computed tomography scan demonstrated cirrhosis, splenomegaly, pancreatic fat infiltration, and a substantial accumulation of peritoneal fluid. Gastroscopy identified esophageal varices. Liver stiffness measurement indicated a value of 32.7 kPa. Based on the results of auxiliary examinations, common causes of cirrhosis were excluded, and a mutation in the Shwachman-Bodian-Diamond syndrome gene was ultimately identified through whole-exome sequencing. The patient was diagnosed with cirrhosis secondary to SDS. Following the correction of hypoalbuminemia and administration of diuretics, the patient's ascites resolved. CONCLUSION Patients with liver cirrhosis who also exhibit pancreatic fat infiltration and pancytopenia necessitate further exon testing to exclude the possibility of SDS.

Chronic Neutrophilic Leukemia with Initial Leukopenia: A Case Report and Review of the Literature

2025-06-23

Sangha Lee , Seul-Bi Lee , Hyun‐Young Kim +5 more | Laboratory Medicine Online

Duffy‐null associated count: Perspectives from the blood Bank

2025-06-23

Helen J. Ross , Zhen Mei , Andrea M. McGonigle +2 more | Transfusion

Persistent Neutropenia and Atopy in an Adolescent: A Subtle Presentation of Phosphoglucomutase 3 Deficiency

2025-06-22

Madalena Fonseca , F. Goncalves Abrantes , Solange Tavares Rubim de Pinho +4 more | Cureus

Piperacillin/tazobactam/Sodium chloride

2025-06-21

| Reactions Weekly

Vancomycin

2025-06-21

| Reactions Weekly

Azithromycin

2025-06-21

| Reactions Weekly

Dipyrone/ofatumumab/peginterferon-beta-1a

2025-06-21

| Reactions Weekly

Piperacillin/tazobactam/zuclopenthixol

2025-06-21

| Reactions Weekly

Cilastatin/imipenem/relebactam

2025-06-21

| Reactions Weekly

Flucloxacillin

2025-06-21

| Reactions Weekly

Vancomycin

2025-06-21

| Reactions Weekly

Bone marrow neutrophil progenitors suppress osteoclast formation in murine cortical and trabecular bone

2025-06-20

Tsuyoshi Isojima , Blessing Crimeen‐Irwin , Narelle E. McGregor +6 more | Blood

In inflammation, circulating neutrophils indirectly damage the skeleton by inducing formation of bone-resorbing osteoclasts. However, neutrophil progenitors in marrow have no known physiological function. A bone-protective role for the neutrophil … In inflammation, circulating neutrophils indirectly damage the skeleton by inducing formation of bone-resorbing osteoclasts. However, neutrophil progenitors in marrow have no known physiological function. A bone-protective role for the neutrophil lineage was recently suggested when a profound defect in bone structure was observed in mice with neutropenia due to Granulocyte Colony Stimulating Factor (G-CSF) deletion coupled with STAT3 hyperactivation in bone cells. Here, we tested the existence of this protective effect by manipulating neutrophil progenitors in bone marrow by Ly6G antibody (aLy6G) treatment. Two protocols revealed an inverse relationship between marrow neutrophil progenitors and osteoclasts. Two weeks of aLy6G treatment increased marrow immature neutrophils by 25% and halved osteoclast mRNA markers in cortical bone. In contrast, coupling six weeks of aLy6G with anti-rat IgG2a to maintain antigenicity reduced marrow pre-neutrophils by 50%. This doubled trabecular osteoclast surface, halved trabecular bone mass, and significantly reduced high density bone mass both in control mice, and in mice with bone-specific STAT3 hyperactivation. In culture, isolated pre-neutrophils dose-dependently inhibited osteoclastogenesis independent of direct contact. We conclude that neutrophil progenitors directly inhibit osteoclast formation by releasing soluble factors. This identifies a novel action of hematopoietic cells in marrow to protect bone structure.

A novel ELANE variant causing severe congenital neutropenia diagnosed in adulthood

2025-06-19

Renato Cerqueira , Josefina Aparecida Pellegrini Braga , Elyse Moritz +2 more | Blood Cells Molecules and Diseases

Manejo controvertido de trombocitopenia grave inducida por abciximab

2025-06-19

María Lasala Alastuey , Isabel Caballero Jambrina , Elena Rivero Fernández +3 more | Revista Argentina de Cardiología

Clinical characteristics and genetic mutation analysis in 18 pediatric patients with Shwachman-Diamond syndrome

2025-06-18

R. Wei , Kaihui Zhang , Chen Liu +7 more | Frontiers in Genetics

Purpose To investigate the clinical features and genetic mutation spectrum of 18 children with Shwachman-Diamond syndrome (SDS). Methods Data from 18 children with SDS at Shandong University Affiliated Children’s Hospital … Purpose To investigate the clinical features and genetic mutation spectrum of 18 children with Shwachman-Diamond syndrome (SDS). Methods Data from 18 children with SDS at Shandong University Affiliated Children’s Hospital (Ji’nan Children’s Hospital) between April 2016 and June 2024 were retrospectively analyzed. Variant sites were confirmed by Sanger sequencing in family lines. Results Patients exhibited complex and diverse clinical symptoms, often involving multiple systems. The clinical features of this cohort included (1) early onset (median age: 1.5 months), diarrhea, trypsin reduction, neutropenia, and growth retardation and (2) high incidence of pancreatic imaging abnormalities, bone marrow hypoplasia, developmental malformations, and neurocognitive disorders. All patients had homozygous or compound heterozygous SBDS mutations, with 258+2T&gt;C identified as the hotspot mutation (20/37), while 41A&gt;T and 185A&gt;C were newly discovered mutations. Conclusion Patients with SDS exhibit clinical heterogeneity, and this study enriches the SBDS gene mutation spectrum. Genetic testing is valuable for early diagnosis.

Afectación de válvula aórtica con endocarditis de Libman- Sacks como debut de síndrome antifosfolipídico secundario

2025-06-18

Nelson E. Polo-Taborda , María V. Verteramo , Fadi A. Nehme +2 more | Revista Colombiana de Cardiología

Impact of lot-to-lot variation in absolute neutrophil count measured by a point-of-care device in patients receiving clozapine treatment

2025-06-18

Mary Kathryn Bohn , B. A. Elliott , Paul S. F. Yip | Clinical Biochemistry

Clozapine is indicated for patients with schizophrenia who are refractory to standard antipsychotic treatment. Due to risk of severe neutropenia, routine monitoring of absolute neutrophil count (ANC) is required. Image-based … Clozapine is indicated for patients with schizophrenia who are refractory to standard antipsychotic treatment. Due to risk of severe neutropenia, routine monitoring of absolute neutrophil count (ANC) is required. Image-based point-of-care devices for ANC measurement in capillary blood present an opportunity to reduce treatment barriers. The objective of this study was to evaluate the impact of lot-to-lot variation on ANC results using a point-of-care device (CSAN® Pronto™). Retrospective patient data were extracted over a 13-month period. Results were classified for treatment safety per vendor as green (≥2.0 × 109/L), yellow (1.5-1.9 × 109/L), or red (<1.5 × 109/L). Distribution of ANC results, flagging rates, and rate and concordance of repeated results were determined. Patient comparisons between a laboratory analyzer (Sysmex XN-10) and Pronto were completed for ANC and WBC for each lot using linear regression and Bland-Altman statistics. 522 patient results across four lots were reviewed. Percentage of results classified as yellow or red varied with lot (yellow: 4.4-10.1 %, red: 2.2-7.8 %). Results for 31 patients were repeated and a reclassification rate of 65 % was observed. Patient comparisons between Pronto and laboratory analyzer for ANC and WBC demonstrated good correlation (Pearson R: ≥0.970). A negative bias was observed for ANC relative to the laboratory that varied with lot (-0.80 to -0.53 × 109/L). The lot with the largest bias demonstrated the highest red alert rate and repeat rate in real-time patient data. Our study combines patient-level data with method comparisons to highlight the impact of lot variation on results with potential consequences, including increased rates of repeated blood sampling. While point-of-care devices may facilitate lowering barriers for clozapine use, provider education and additional quality metrics are needed to inform testing.

A case report of septic shock caused by opportunistic infections associated with anti-interferon-γ autoantibody positivity: diagnostic and therapeutic challenges

2025-06-13

Jinlian Shao , Xiaohong Xu , Xiande Xie +3 more | Frontiers in Medicine

Background Since 2004, there has been an increasing number of reports on severe, persistent, or recurrent Salmonella infections in adults with adult immunodeficiency associated with anti-gamma interferon antibody positivity (AIGA). … Background Since 2004, there has been an increasing number of reports on severe, persistent, or recurrent Salmonella infections in adults with adult immunodeficiency associated with anti-gamma interferon antibody positivity (AIGA). AIGA patients experience rapid disease progression upon infection with opportunistic pathogens, high mortality rates, and strong disease latency, posing significant challenges for diagnosis and treatment. This article discusses the diagnosis and treatment strategies for AIGA with opportunistic pathogen infection through the diagnosis and treatment process of a 61-year-old male patient. Methods The patient presented with diarrhea and fever for 2 weeks and was diagnosed with non-typhoidal Salmonella infection at an external hospital. The condition progressed to shock and the patient was transferred to our EICU. After admission, the pathogens were confirmed through chest CT, blood culture, blood metagenomic next-generation sequencing (mNGS), and bronchoalveolar lavage fluid (BALF) mNGS, and cell immune function screening and anti-gamma interferon antibody testing were completed. The anti-infective treatment regimen was adjusted based on the test results, and immunoglobulin therapy was administered. Results The patient’s blood culture was positive for non-typhoidal Salmonella, and blood mNGS confirmed non-typhoidal Salmonella and Legionella pneumophila ; BALF mNGS showed Enterococcus faecium , Legionella pneumophila , Candida tropicalis , Candida glabrata, HSV1, and CMV mixed infection. Immune function screening indicated a significant decrease in CD4 + T cells (303 cells/μL) and a significant increase in anti-gamma interferon antibody (163.78 ng/mL), confirming the diagnosis of AIGA. After treatment with meropenem, linezolid, doxycycline, ganciclovir, and caspofungin combined with anti-infective and immunoglobulin therapy, the patient’s condition significantly improved and was discharged. Conclusion AIGA patients experience rapid disease progression after infection with opportunistic pathogens. Early identification of anti-gamma interferon antibody and mixed infection pathogens is crucial for treatment.

Acute kidney injury after pegylated granulocyte colony-stimulating factor and dexamethasone

2025-06-12

Osamu Imataki , Shunsuke Yoshida , Shinichiro Hashimoto +1 more | Supportive Care in Cancer

Anti‐thymocyte globulin in immune‐mediated cytopenias: A monocentric experience and literature review

2025-06-12

Luca Guarnera , Arooj Ahmed , Carlos Bravo‐Pérez +7 more | British Journal of Haematology

Anti-thymocyte globulin in multi-refractory immune-mediated cytopenia is an effective treatment, with response rate as high as 65%. Younger patients, presenting with thrombocytopenia or neutropenia, and those with LGL and STAT3 … Anti-thymocyte globulin in multi-refractory immune-mediated cytopenia is an effective treatment, with response rate as high as 65%. Younger patients, presenting with thrombocytopenia or neutropenia, and those with LGL and STAT3 mutations appear to be more likely responsive.

Acquired Bernard-Soulier syndrome as the presenting feature of GATA2-related myeloid neoplasm in an adolescent: an insight into the mechanisms underlying the platelet defect

2025-06-05

Laureano J. Kamiya , M Morell , Rosana F. Marta +7 more | Haematologica

Not available. Not available.

Spontaneous Pneumothorax as an Evolutionary Manifestation of Rheumatoid Arthritis: A Case Report and Review of the Literature

2025-06-04

N. Zaghba , A. Amir , Hanaa Harraz +4 more | SAS Journal of Medicine

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that can lead to pulmonary involvement, particularly subpleural nodules. We report the case of a 28-year-old patient with seropositive RA who developed … Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that can lead to pulmonary involvement, particularly subpleural nodules. We report the case of a 28-year-old patient with seropositive RA who developed a spontaneous left-sided pneumothorax. Chest CT revealed excavated pulmonary nodules. The evolution was favorable after thoracic drainage. Anti-TNF alpha biotherapy was initiated after exclusion of active tuberculosis. This case illustrates a rare but serious complication of RA. It highlights the importance of pulmonary surveillance in these patients.

Schwerwiegende Late-onset-Neutropenien nach Rituximab-Gabe

2025-06-04

Christian Schütte , Christiana Hillebrecht , Jens G. Kuipers +3 more | Zeitschrift für Rheumatologie

ABS0518 A COMPARATIVE ANALYSIS OF PRIMARY AND SECONDARY ANTIPHOSPHOLIPID SYNDROME IN A GREEK COHORT: EVALUATING PATIENTS WITH DIVERSE THROMBOTIC PHENOTYPES

2025-06-01

V. Lainis , Michail Krikelis , O. Katsouli +1 more | Annals of the Rheumatic Diseases

ABS0406 RISK OF NEUTROPENIA AND T-CELL CLONAL EXPANSION IN RHEUMATOID ARTHRITIS PATIENTS ON TNF INHIBITORS

2025-06-01

Anastasia Mocritcaia , O. Omaña , Alberto Rivero +2 more | Annals of the Rheumatic Diseases

Piperacillin-induced encephalopathy

2025-06-01

Pedro Parra-Caballero , Ángela Sánchez-Juez , Francisco Abad-Santos | Medicina Clínica (English Edition)

OP0267 SINGLE-CELL TRANSCRIPTOMICS OF B CELLS TOWARDS THE UNDERSTANDING OF THE MECHANISMS LEADING TO THE PRODUCTION OF ANTIPHOSPHOLIPID ANTIBODIES IN THROMBOTIC PRIMARY ANTIPHOSPHOLIPID SYNDROME

2025-06-01

Pedro Gaspar , D. Holdych , Mariane Santos +7 more | Annals of the Rheumatic Diseases

UPDATED EFFICACY & SAFETY OF BTK DEGRADER BGB‐16673 IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINEMIA (R/R WM): ONGOING PHASE 1 CaDAnCe‐101 RESULTS

2025-06-01

Anna Maria Frustaci , J.F. Seymour , Chan Y. Cheah +7 more | Hematological Oncology

De novo myeloid sarcoma of the oral cavity in early adolescence: an uncommon presentation with severe congenital neutropenia

2025-06-01

N. Jayakumar , Deenadayalan Munirathnam , Meena Sivasankaran +3 more | BMJ Case Reports

Severe congenital neutropenia (SCN) is a rare disorder characterised by a persistent decrease in circulating leukocytes leading to recurrent life-threatening bacterial and fungal infections. SCN patients also carry an inherent … Severe congenital neutropenia (SCN) is a rare disorder characterised by a persistent decrease in circulating leukocytes leading to recurrent life-threatening bacterial and fungal infections. SCN patients also carry an inherent risk of developing malignancies and myelodysplastic transformations, which can be attributed to increased clonal haematopoiesis. Though the incidence of acute myeloid leukaemia in SCN patients is well documented in literature, the occurrence of extramedullary lesions like myeloid sarcoma is an uncommon event. Here we present a comprehensive case report of a female in early adolescence with SCN presenting with myeloid sarcoma of the mandible.

Diagnosis and management of cutaneous infections in immunocompromised hosts part II: neutropenia and humoral immunodeficiency

2025-06-01

Nicole Boswell , Nina Punyamurthy , Kiran Motaparthi +2 more | Journal of the American Academy of Dermatology