scholarly journals Granulocyte transfusions: current status

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 2-8
Author(s):  
DJ Higby ◽  
D Burnett
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Clinical Medicine ◽  
Bone Marrow Failure ◽  
Current Status ◽  
Granulocyte Transfusion ◽  
Transfusion Therapy ◽  
Neutropenic Patients ◽  
Ongoing Evaluation ◽  
Made In

Since granulocyte transfusions first became widely used in clinical medicine, there have been advances in the treatment of acute leukemia and improvement in prevention and management of infection in neutropenic patients. Improved understanding now exists concerning prognosis of infections in such patients, and advances have been made in procurement of granulocytes. Granulocyte transfusions should be given for specific indications, and used adjunctively to other established antiinfective therapy. Once initiated, transfusions should be given in adequate doses at daily intervals (at least) with ongoing evaluation and periodic reassessment of the whole antiinfective program. Serious complications of granulocyte transfusion therapy are relatively rare, but the physician should be prepared to manage them intelligently. Research continues in discerning exactly how granulocyte transfusion work, in preservation of granulocytes, and in delineation of immunologic phenomena affecting the efficiacy of such therapy. Granulocyte transfusions will continue to be important in the management of acute leukemia, and other reversible bone marrow failure states, and in marrow transplantation and autotransplantation.

scholarly journals Granulocyte transfusions: current status

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 2-8 ◽  
Author(s):  
DJ Higby ◽  
D Burnett
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Clinical Medicine ◽  
Bone Marrow Failure ◽  
Current Status ◽  
Granulocyte Transfusion ◽  
Transfusion Therapy ◽  
Neutropenic Patients ◽  
Ongoing Evaluation ◽  
Made In

Abstract Since granulocyte transfusions first became widely used in clinical medicine, there have been advances in the treatment of acute leukemia and improvement in prevention and management of infection in neutropenic patients. Improved understanding now exists concerning prognosis of infections in such patients, and advances have been made in procurement of granulocytes. Granulocyte transfusions should be given for specific indications, and used adjunctively to other established antiinfective therapy. Once initiated, transfusions should be given in adequate doses at daily intervals (at least) with ongoing evaluation and periodic reassessment of the whole antiinfective program. Serious complications of granulocyte transfusion therapy are relatively rare, but the physician should be prepared to manage them intelligently. Research continues in discerning exactly how granulocyte transfusion work, in preservation of granulocytes, and in delineation of immunologic phenomena affecting the efficiacy of such therapy. Granulocyte transfusions will continue to be important in the management of acute leukemia, and other reversible bone marrow failure states, and in marrow transplantation and autotransplantation.

Granulocyte Transfusion Therapy: Survival Directly Correlated with Bone Marrow Recovery and the Pathogenicity of the Infectious Organisms

1981 ◽  
Vol 146 (6) ◽  
pp. 393-396
Author(s):  
James E. Congdon ◽  
Glen R. Justice ◽  
Irwin Dabe ◽  
Eugene P. Flannery ◽  
Michael P. Corder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Granulocyte Transfusion ◽  
Transfusion Therapy

Marrow Failure

Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 318-336 ◽  
Author(s):  
Grover C. Bagby ◽  
Jeffrey M. Lipton ◽  
Elaine M. Sloand ◽  
Charles A. Schiffer
Keyword(s):  
Bone Marrow ◽  
Immunosuppressive Therapy ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Allogeneic Bone Marrow Transplantation ◽  
Dyskeratosis Congenita ◽  
Allogeneic Bone ◽  
Diagnosis And Management ◽  
Bone Marrow Failure Syndromes ◽  
Made In

Abstract New discoveries in cell biology, molecular biology and genetics have unveiled some of the pathophysiological mysteries of some of the bone marrow failure syndromes. Many of these discoveries have revealed why these syndromes show so much clinical overlap and some hold the potential for influencing the development of new therapies. In children and adults with pancytopenia and hypoplastic bone marrows proper differential diagnosis requires that some attention be directed toward defining molecular and cellular pathogenetic mechanisms because, once identified, some of these mechanisms will clearly suggest rational therapeutic approaches, treatment options that should be avoided, or both. In Section I, Drs. Jeffrey Lipton and Grover Bagby review the approach to diagnosis and management of patients with the inherited bone marrow failure syndromes, Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and the Shwachman-Diamond syndrome. Extraordinary progress has been made in identifying the genes bearing pathogenetically relevant mutations in these disorders, but slower progress has been made in defining the precise functions of the proteins these genes encode in normal cells, in part because it is increasingly obvious that the proteins are multifunctional. In practice, it is clear that in patients with dyskeratosis congenita and Fanconi anemia, the diagnosis must be considered not only in children but in adults as well. In Section II, Dr. Elaine Sloand outlines a very practical and evidence-based approach to diagnosis and management of acquired hypoplastic states emphasizing overlap between non-clonal and clonal hematopoiesis is such conditions. The pathogenesis of T lymphocyte–mediated marrow failure is presented as a clear-cut rationale for use of immunosuppressive therapy and stem cell transplantation. Practical management of patients with refractory disease with and without evidence of clonal evolution (either paroxysmal nocturnal hemoglobinuria [PNH] or myelodysplasia [MDS]) is presented. In Section III, the challenge of hypoplastic MDS is reviewed by Dr. Charles Schiffer. After reviewing the most up-to-date classification scheme, therapeutic options are reviewed, focusing largely on agents that have most recently shown some promising activity, including DNA demethylating agents, thalidomide and CC5013, arsenic trioxide, and immunosuppressive therapy. Here are also outlined the rationale and the indications for choosing allogeneic bone marrow transplantation, the only therapy with known curative potential.

Characteristics of De Novo Acute Leukemia Patients with Glycosylphosphatidylinositol (GPI) Protein-Negative Population of Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4462-4462
Author(s):  
Hideyoshi Noji ◽  
Tsutomu Shichishima ◽  
Masatoshi Okamoto ◽  
Kazuhiko Ikeda ◽  
Akiko Nakamura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
De Novo ◽  
Bone Marrow Failure ◽  
Flow Cytometric Analysis ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Color Flow ◽  
Flow Cytometric ◽  
Number Of Patients

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be an acquired stem cell disorder affecting all hematopoietic lineages, which lack GPI-anchored membrane proteins, such as CD59, because of abnormalities in the phosphatidylinositol glycan-class A (PIG-A) gene. Also, PNH is one disorder of bone marrow failure syndromes, including aplastic anemia and myelodysplastic syndrome, which are considered as pre-leukemic states. In this study, to know some characteristics of patients with de novo acute leukemia, we investigated expression of CD59 in leukemic cells from 25 patients (female: male=8: 17; mean age ± standard deviation, 57.8 ± 19.5 years) with de novo acute leukemia by single-color flow cytometric analysis. In addition, the PIG-A gene from CD59− leukemic cells sorted by FACS Vantage in 3 patients with acute leukemia was examined by sequence analysis. All the patients had no past history of PNH. Based on the French-American-British criteria, the diagnosis and subtypes of acute leukemia were determined. The number of patients with subtypes M1, M2, M3, M4, M5, and M7 was 1, 14, 2, 4, 2, and 2, respectively. Two of the patients were classified into acute myeloid leukemia with trilineage myelodysplasia from morphological findings in bone marrow. Chromosomal analyses presented abnormal karyotypes in 14 of 25 patients. Flow cytometric analyses showed that leukemic cells from 16 of 25 patients (64%) had negative populations of CD59 expression and the proportion of the populations was 63.3 ± 25.7%, suggesting the possibility that CD59− leukemic cells from patients with de novo acute leukemia might be derived from PNH clones. In fact, the PIG-A gene analyses showed that monoclonal or oligoclonal PIG-A mutations in coding region were found in leukemic cells from 3 patients with CD59− leukemic cells and all of the clones with the PIG-A mutations were minor. Then, various clinical parameters, including rate of complete remission for remission-induction chemotherapy, peripheral blood, bone marrow blood, and laboratory findings, and results of chromosomal analyses were statistically compared between 2 groups of patients with (n=16) and without (n=9) CD59− leukemic cells. The reticulocyte counts (10.5 ± 13.0 x 104/μl) and proportions of bone marrow erythroblasts (17.5 ± 13.9%) in patients with only CD59+ leukemic cells were significantly higher than those (2.5 ± 1.7 x 104/μl, p<0.05; and 5.6 ± 6.2%, p<0.01, respectively) in patients with CD59− leukemic cells. The proportions of bone marrow blasts (69.3 ± 21.1%) in patients with CD59− leukemic cells were significantly higher than those (45.5 ± 19.3%, p<0.02) in patients with only CD59+ leukemic cells. In conclusion, our findings indicate that leukemic cells derived from PNH clones may be common in de novo acute leukemia patients, suggesting that bone marrow failure may have already occurred in localized bone marrow even in de novo acute leukemia.

Study of the Correlation between Phenotype - Including Acute Leukemia/MDS- and Genotype in Shwachman Diamond Syndrome in 60 Patients from the French SCN Registry.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3301-3301
Author(s):  
Jean Donadieu ◽  
B. Beaupain ◽  
S. Beaufils ◽  
V. Gandemer ◽  
J.P. Fermant ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Survival Data ◽  
Bone Marrow Failure ◽  
Great Majority ◽  
Rank Test ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Specialized School ◽  
Shwachman Diamond Syndrome

Abstract Shwachman Diamond syndrome (SDS) is a rare multi organ genetic disease bearing a very high risk of haematological complications i.e. MDS/leukaemia and Bone Marrow Failure. The aim of this study is to explore genotype predisposition of the major complications observed in SDS’s patients and to explore prognosis factors of MDS/leukaemia. Methods: Among 90 SDS patients included in the French Severe Chronic Neutropenia Registry, SBDS gene was screened in 63 patients and mutations have been found in 60 patients. Cut-off date was july 30th, 2007. Differences between groups of patients were analysed as survival data, by log rank test. The medical events analysed were: death (n=6), myelodysplasia or acute leukemia (n=6), bone marrow failure (n=6), all hematological events combined (n=12), the use of G-CSF as infectious prophylaxis (n= 11), the necessity of an orthopedic surgery (n=4) and the necessity of nutritional medical support (parenteral or enteral feeding, by mean of gastrostomy (n= 5), intrauterine growth retardation (n=19) and finally, major development retardation if it leads to a specialized school (n=10). Results: Mutations were found in 60 patients (35 males, 25 females) belonging to 54 distinct families (in 6 families, two siblings were genotyped). The median age at last analysis was 10.3 years (0.5yr-38.6 yr). The great majority of patients present the recurrent genotype K62X/C84fs (n=38, 68%) while 19 other mutations were founded, which could be classified in truncating mutations leading to premature stop codons (nonsense, frameshift or splicing defect; n=8) or missense mutations (n=11). We compared patients with truncating mutations on both alleles to compound heterozygous patients carrying at least one missense mutation. Even if differences were observed for the distribution of events between genotype subgroups of patients, none of them raised statistically significance. However, to date, all leukemia has been observed in the group of patients with “truncating” mutations. The genotype of patients with leukemia was [K62X]+[C84fs] in 5 and [C84fs]+[V93fs] in one; while the genotype of patients with BM failure was [K62X]+[C84fs] (n=2), [C84fs]+[624+1G>C], [C84fs]+[C119R], K62X/undetermined, and [C84fs]+[E99fs], [C84fs]+[E44fs]. Among the 6 pairs of siblings tested, four had a similar outcome and two pairs were discordant for the haematological events (leukaemia in one family, Bone marrow failure in the second family). Further, we have analysed genotype, gender, G-CSF therapy and initial Neutrophils and monocytes count, Hemoglobin level, Platelet level as risk factors of Leukemia/MDS. In a multivariate model, none of these features predicts Leukemia/MDS in SDS patients. Conclusion: The genotype of SDS did not appear to be correlated with clinical presentation or outcome. It remains possible than patients without truncating mutations (about 18%) may have a low rate of leukaemia but our survey lack of statistical powerful to demonstrate this hypothesis. We also failed to determine prognostic factors of Leukemia/MDS in SDS patients.

Current Concepts of the Pathogenesis of Aplastic Anemia

2019 ◽  
Vol 25 (3) ◽  
pp. 236-241 ◽  
Author(s):  
Chunyan Liu ◽  
Yingying Sun ◽  
Zonghong Shao
Keyword(s):  
Bone Marrow ◽  
Dendritic Cell ◽  
Aplastic Anemia ◽  
Chromosomal Abnormalities ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Bone Marrow Failure ◽  
Plasmacytoid Dendritic Cell ◽  
Current Status ◽  
Telomere Attrition

Abnormal activation of the immune system plays an important role in the pathogenesis of aplastic anemia (AA). Various immune cells and cytokines constitute a complex immune network, leading to bone marrow failure. The known pathogenesis is an increase of the myeloid dendritic cell (mDC)/ plasmacytoid dendritic cell (pDC) ratio, which causes the ratio of T helper (Th)1/Th2 to be skewed in favor of Th1 and eventually leads to an abnormal activation of cytotoxic T lymphocyte (CTL). The antigens that stimulate T cells in the context of AA remain unknown. In this process, regulatory T (Treg), Th17, natural killer (NK) cell, memory T cell and negative hematopoietic regulatory factors are also involved. In addition, genetic background (e.g., chromosomal abnormalities, telomere attrition, somatic cell mutations), abnormal bone marrow hematopoietic microenvironment and viral infection may also contribute to the pathogenesis of AA. This review summarizes the recent studies of the pathogenesis of AA and the current status of AA research.

Hematogones Detected by Flow Cytometry in a Child with Vitamin B12 Deficiency

2017 ◽  
Vol 20 (2) ◽  
pp. 172-175
Author(s):  
Lisa Sutton ◽  
Nkechi Mba
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Leukemia ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Bone Marrow Failure ◽  
Vitamin B12 Deficiency ◽  
Bone Marrow Biopsies ◽  
B12 Deficiency ◽  
B Cell Precursors

Vitamin B12 deficiency is a known cause of megaloblastic anemia and bone marrow failure. Bone marrow biopsies are not frequently performed as part of the diagnostic workup and can demonstrate morphologic features that overlap with myelodysplastic syndrome (MDS) and acute leukemia. We describe a case of a dysplastic bone marrow with increased bone marrow hematogones detected by flow cytometry in a child with vitamin B12 deficiency. Hematogones are normal B cell precursors, and hyperplasia has been described in a variety of often reactive conditions and also disease. Hematogones are not typically seen in MDS. The presence of hematogones may help differentiate the dysplastic changes seen in vitamin B12 deficiency from MDS.

scholarly journals Genetic classification and confirmation of inherited platelet disorders: current status in Korea

2020 ◽  
Vol 63 (3) ◽  
pp. 79-87 ◽  
Author(s):  
Ye Jee Shim
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Failure ◽  
Gene Mutations ◽  
Hematologic Malignancies ◽  
Mendelian Inheritance ◽  
Current Status ◽  
Genetic Classification ◽  
Granule Formation ◽  
Primary Hemostasis ◽  
Platelet Disorders

Inherited platelet disorders (IPDs), which manifest as primary hemostasis defects, often underlie abnormal bleeding and a family history of thrombocytopenia, bone marrow failure, hematologic malignancies, undefined mucocutaneous bleeding disorder, or congenital bony defects. Wide heterogeneity in IPD types with regard to the presence or absence of thrombocytopenia, platelet dysfunction, bone marrow failure, and dysmegakaryopoiesis is observed in patients. The individual processes involved in platelet production and hemostasis are genetically controlled; to date, mutations of more than 50 genes involved in various platelet biogenesis steps have been implicated in IPDs. Representative IPDs resulting from defects in specific pathways, such as thrombopoietin/MPL signaling; transcriptional regulation; granule formation, trafficking, and secretion; proplatelet formation; cytoskeleton regulation; and transmembrane glycoprotein signaling are reviewed, and the underlying gene mutations are discussed based on the National Center for Biotechnology Information database and Online Mendelian Inheritance in Man accession number. Further, the status and prevalence of genetically confirmed IPDs in Korea are explored based on searches of the PubMed and KoreaMed databases. IPDs are congenital bleeding disorders that can be dangerous due to unexpected bleeding and require genetic counseling for family members and descendants. Therefore, the pediatrician should be suspicious and aware of IPDs and perform the appropriate tests if the patient has unexpected bleeding. However, all IPDs are extremely rare; thus, the domestic incidences of IPDs are unclear and their diagnosis is difficult. Diagnostic confirmation or differential diagnoses of IPDs are challenging, time-consuming, and expensive, and patients are frequently misdiagnosed. Comprehensive molecular characterization and classification of these disorders should enable accurate and precise diagnosis and facilitate improved patient management.

scholarly journals Corticosteroids Impair Granulocyte Transfusion Therapy By Targeting NET Formation and Neutrophil Antifungal Functions Via ROS/Dectin1 Pathways

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2506-2506 ◽  
Author(s):  
Natarajaswamy Kalleda ◽  
Jorge Amich ◽  
Spoorthi Poreddy ◽  
Berkan Arslan ◽  
Mike Friedrich ◽  
...  
Keyword(s):  
Mouse Models ◽  
Defense Mechanisms ◽  
Fungal Infections ◽  
Corticosteroid Treatment ◽  
High Morbidity ◽  
Granulocyte Transfusion ◽  
Transfusion Therapy ◽  
Neutropenic Patients

Abstract Introduction: Invasive pulmonary Aspergillus fumigatus infections cause high morbidity and mortality in neutropenic patients. Granulocyte transfusions have been tested as an alternative therapy for the management of high-risk neutropenic patients with invasive A. fumigatus infections. To increase the granulocyte yield for transfusion, donors are treated with corticosteroids. Yet, the efficacy of granulocyte transfusion and functional defense mechanisms of granulocytes collected from corticosteroid treated donors remain largely elusive. Therefore, we investigated the efficacy of granulocyte transfusion and functional defense mechanisms of corticosteroid treated granulocytes using mouse models. Methods: To determine the effects of corticosteroids on granulocytes to control A. fumigatus infections, we performed granulocyte adoptive cell transfers using in vivo mouse models, in vitro human and mouse granulocyte and A. fumigatus functional co-culture experiments in combination with flow cytometry, cytokine analysis, fluorescence and electron microscopy. Results: Transfusion of granulocytes from corticosteroid treated mice did not protect cyclophosphamide immunosuppressed mice against lethal A. fumigatus infection in contrast to granulocytes from untreated mice. Upon infection increased levels of inflammatory cytokines helped to recruit granulocytes to the lungs without any recruitment defects in corticosteroid treated and infected mice or in cyclophosphamide immunosuppressed and infected mice that had received the granulocytes from corticosteroid treated mice. However, corticosteroid treated human or mouse neutrophils failed to form neutrophil extracellular traps (NETs) under in vitro and in vivo conditions. Furthermore, corticosteroid treated granulocytes exhibited impaired ROS production against A. fumigatus. Notably, corticosteroids impaired the β-glucan receptor Dectin-1 (CLEC7A) on mouse and human granulocytes to efficiently recognize and phagocytize A. fumigatus, which markedly impaired fungal killing. Conclusions: We conclude that corticosteroid treatment of granulocyte donors for increasing neutrophil yields or patients with ongoing corticosteroid treatment could result in deleterious effects on granulocyte antifungal functions, thereby limiting the benefit of granulocyte transfusion therapies against invasive fungal infections. Disclosures Einsele: Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Speakers Bureau.

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