-
Haematologica Jan 2021
Topics: Bone Marrow Failure Disorders; Genomics; Humans; Pancytopenia
PubMed: 33386715
DOI: 10.3324/haematol.2020.265124 -
The Veterinary Record Jan 2023
Topics: Cats; Animals; Pancytopenia; Cat Diseases
PubMed: 36661151
DOI: 10.1002/vetr.2647 -
JPMA. the Journal of the Pakistan... Sep 2022To determine the aetiologies of pancytopenia based on bone trephine biopsy among paediatric and adult patients.
OBJECTIVE
To determine the aetiologies of pancytopenia based on bone trephine biopsy among paediatric and adult patients.
METHOD
The retrospective cross-sectional study was conducted at the Haematology Department of Aga Khan University Hospital, Karachi, and comprised data from June 1, 2016, to October 31, 2019 related to pancytopenia patients who underwent bone marrow biopsy. Data included age, gender, presenting symptoms, physical examination, complete blood count, peripheral smear, bone marrow aspirate and trephine biopsy findings and final diagnosis. Data was analysed using SPSS 19.
RESULTS
Of the 2852bone marrow biopsies done, 255(9%) related to evaluation of pancytopenia. Of them, 208(82%) were adult and 47(18%) were paediatric patients. The median age for adults was 38.8 years (range: 16-92years) and that in paediatric patients was 10.9 years (range: 2-15 years). Presenting symptoms were available for 182(71.4%) patients, and the commonest symptom was generalised weakness 128(70.3%). Overall, pallor was the most frequent sign 233(93.2%). Anisocytosis was predominant blood smear finding 156(61.1%), while the commonest aetiology was aplastic anaemia in both paediatric 23(49%) and adult 57(27.4%) groups. Bone marrow biopsy established the diagnosis in 253(99.2%) cases, while 2(0.95%) adult cases were not diagnosed. Of the diagnosed cases, 103(40.4%) were malignant; 15(32%) paediatric patients and 88(42.3%) adults. The rest were benign; 31(67.4%) paediatric patients and 119(3%) adults.
CONCLUSIONS
Bone marrow biopsy helped in diagnosing all but 2 pancytopenic patients. Aplastic anaemia was the commonest cause in both paediatric and adult patients.
Topics: Adult; Child; Humans; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Pancytopenia; Bone Marrow; Bone Marrow Examination; Anemia, Aplastic; Retrospective Studies; Cross-Sectional Studies; Biopsy
PubMed: 36280982
DOI: 10.47391/JPMA.2092 -
Proceedings of the National Academy of... Jan 2024Human bone marrow failure (BMF) syndromes result from the loss of hematopoietic stem and progenitor cells (HSPC), and this loss has been attributed to cell death;...
Human bone marrow failure (BMF) syndromes result from the loss of hematopoietic stem and progenitor cells (HSPC), and this loss has been attributed to cell death; however, the cell death triggers, and mechanisms remain unknown. During BMF, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) increase. These ligands are known to induce necroptosis, an inflammatory form of cell death mediated by RIPK1, RIPK3, and MLKL. We previously discovered that mice with a hematopoietic RIPK1 deficiency () exhibit inflammation, HSPC loss, and BMF, which is partially ameliorated by a RIPK3 deficiency; however, whether RIPK3 exerts its effects through its function in mediating necroptosis or other forms of cell death remains unclear. Here, we demonstrate that similar to a RIPK3 deficiency, an MLKL deficiency significantly extends survival and like Ripk3 deficiency partially restores hematopoiesis in mice revealing that both necroptosis and apoptosis contribute to BMF in these mice. Using mouse models, we show that the nucleic acid sensor Z-DNA binding protein 1 (ZBP1) is up-regulated in mouse RIPK1-deficient bone marrow cells and that ZBP1's function in endogenous nucleic acid sensing is necessary for HSPC death and contributes to BMF. We also provide evidence that IFNγ mediates HSPC death in mice, as ablation of IFNγ but not TNFα receptor signaling significantly extends survival of these mice. Together, these data suggest that RIPK1 maintains hematopoietic homeostasis by preventing ZBP1 activation and induction of HSPC death.
Topics: Animals; Humans; Mice; Apoptosis; Bone Marrow Failure Disorders; Cell Death; Hematopoietic Stem Cells; Necrosis; Nucleic Acids; Pancytopenia; Receptor-Interacting Protein Serine-Threonine Kinases
PubMed: 38227660
DOI: 10.1073/pnas.2309628121 -
Hematology/oncology and Stem Cell... Nov 2022Chimeric antigen receptor T-cell (CAR T-cell) therapy represents an innovative and transformative therapy for patients with relapsed and/or refractory (R/R)... (Review)
Review
Chimeric antigen receptor T-cell (CAR T-cell) therapy represents an innovative and transformative therapy for patients with relapsed and/or refractory (R/R) hematological malignancies. CAR T-cell therapy was first approved in R/R diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia, today the use of CAR T-cell therapy has expanded to multiple myeloma and other lymphoma subtypes such as follicular and mantle cell lymphoma. It is also being explored in earlier lines of therapy in DLBCL. CAR T-cell therapy is associated with a unique toxicity profile and development of cytopenias post CAR T-cell therapy has been reported in all pivotal clinical trials and is now considered a related side effect. Here, we provide an in-depth evaluation of etiologies, consequences, and current management strategies for cytopenias following CAR T-cell therapy.
Topics: Humans; Adult; Immunotherapy, Adoptive; Pancytopenia; Receptors, Chimeric Antigen; T-Lymphocytes; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Anemia; Thrombocytopenia; Receptors, Antigen, T-Cell
PubMed: 36633964
DOI: 10.56875/2589-0646.1047 -
International Journal of Molecular... Oct 2022In recent years, it has become increasingly apparent that bone marrow (BM) failures and myeloid malignancy predisposition syndromes are characterized by a wide... (Review)
Review
In recent years, it has become increasingly apparent that bone marrow (BM) failures and myeloid malignancy predisposition syndromes are characterized by a wide phenotypic spectrum and that these diseases must be considered in the differential diagnosis of children and adults with unexplained hematopoiesis defects. Clinically, hypocellular BM failure still represents a challenge in pathobiology-guided treatment. There are three fundamental topics that emerged from our review of the existing data. An exogenous stressor, an immune defect, and a constitutional genetic defect fuel a vicious cycle of hematopoietic stem cells, immune niches, and stroma compartments. A wide phenotypic spectrum exists for inherited and acquired BM failures and predispositions to myeloid malignancies. In order to effectively manage patients, it is crucial to establish the right diagnosis. New theragnostic windows can be revealed by exploring BM failure pathomechanisms.
Topics: Adult; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Hematopoietic Stem Cells; Humans; Pancytopenia; Workflow
PubMed: 36233062
DOI: 10.3390/ijms231911765 -
Modern Rheumatology Case Reports Jan 2023Pachydermaperiostosis (PDP) is a rare condition of connective tissue presenting with abnormal skin and skeletal findings that usually occur as a complication of an...
Pachydermaperiostosis (PDP) is a rare condition of connective tissue presenting with abnormal skin and skeletal findings that usually occur as a complication of an underlying disease, especially malignancies. We described a case of a patient with severe transfusion-dependent anemia and both skin and joint findings, diagnosed as PDP. The haematological assessment revealed myelofibrosis as the underlying disease, and treatment with ruxolitinib as the first-line choice was given by skipping hydroxyurea due to pancytopenia. The patient got benefits in arthralgia and amelioration of pancytopenia and a reduced spleen volume was observed, despite the negative result for JAK2 gene mutation. This is the first case of ruxolitinib being used in PDP with myelofibrosis, and it highlights the importance of evaluating PDP as not just a skin and joint problem but a result of systemic disease and individual-based treatment.
Topics: Humans; Primary Myelofibrosis; Pancytopenia; Nitriles; Pyrimidines
PubMed: 36208298
DOI: 10.1093/mrcr/rxac076 -
Environmental Pollution (Barking, Essex... Oct 2022Benzene exposure can cause pancytopenia and immunosuppression, leading to serious diseases such as aplastic anemia (AA) or acute myeloid leukemia (AML), but the...
Benzene exposure can cause pancytopenia and immunosuppression, leading to serious diseases such as aplastic anemia (AA) or acute myeloid leukemia (AML), but the underlying mechanism has not been fully elucidated. Hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that regulates many downstream target genes. In this study, we reported a novel mechanism by which high expression of HIF-1α alleviated benzene toxicity. Mice with high expression of HIF-1α (HIF-1α) were obtained by the Tet-on system and doxycycline induction, and they and wild-type (WT) mice were exposed to 150 mg/kg benzene for 0, 1, 3, 7, 10, 14, and 28 days. Dynamic changes in hematopoietic and immune-related indicators and the role of HIF-1α were explored. The level of white blood cells in mice reached the highest level on the third day, and immunity was activated and then suppressed within 10 days. Significant pancytopenia and immunosuppression occurred at 14 days and were more pronounced at 28 days. The levels of HIF-1α, EPO, VEGF, RORγt, and IL-17 in WT mice gradually decreased with increasing benzene exposure days, while the levels of Foxp3 and IL-10 increased. These changes were alleviated in HIF-1α mice. High expression of HIF-1α increased the levels of EPO and VEGF, which helped to maintain the stability of the hematopoietic microenvironment. Simultaneously, it attenuated benzene-induced immunosuppression by alleviating the Th17/Treg imbalance. HIF-1α is expected to be a new target for benzene-induced diseases such as AA and AML.
Topics: Animals; Benzene; Hypoxia-Inducible Factor 1, alpha Subunit; Immunosuppression Therapy; Leukemia, Myeloid, Acute; Mice; Pancytopenia; Tumor Microenvironment; Vascular Endothelial Growth Factor A
PubMed: 35970343
DOI: 10.1016/j.envpol.2022.119928 -
Leukemia Research Jun 2023The accrual of somatic mutations is a byproduct of aging. When a clone bearing a somatic genetic alteration, conferring comparative competitive advantage, displays...
The accrual of somatic mutations is a byproduct of aging. When a clone bearing a somatic genetic alteration, conferring comparative competitive advantage, displays sufficient outgrowth to become detectable amongst an otherwise polyclonal background in the hematopoietic system, this is called clonal hematopoiesis (CH). Somatic genetic alterations observed in CH include point mutations in cancer related genes, mosaic chromosomal alterations or a combination of these. Interestingly, clonal hematopoiesis (CH) can also occur with somatic variants in genes without a known role in cancer and in the absence of a somatic genetic alteration through a process that has been described as 'genetic drift'. Clonal hematopoiesis of indeterminate significance (CHIP), is age-related and defined by the presence of somatic point mutations in cancer related genes, in the absence of cytopenias or a diagnosis of hematologic neoplasm, with a variant allele fraction ≥ 2 %. Remarkably, the increased mortality associated with CHIP is largely due to cardiovascular disease. Subsequently, CHIP has been associated with a myriad of age-related conditions such as Alzheimer's Disease, osteoporosis, CVA and COPD. CHIP is associated with an increased risk of hematologic malignancies, particularly myeloid neoplasms, with the risk rising with increasing clone size and clonal complexity. Mechanisms regulating clonal evolution and progression to hematologic malignancies remain to be defined. However, observations on context specific CH arising in the setting of bone marrow failure states, or on exposure to chemotherapy and radiation therapy, suggest that CH reflects context specific selection pressures and constraint-escape mechanisms.
Topics: Humans; Clonal Hematopoiesis; Hematopoiesis; Hematologic Neoplasms; Pancytopenia; Myeloproliferative Disorders; Clonal Evolution; Mutation
PubMed: 37075557
DOI: 10.1016/j.leukres.2023.107076 -
Deutsche Medizinische Wochenschrift... Jan 2022The 79-year-old patient was admitted with recurring fever, weight loss, night sweat, a decrease in physical capacity and hematomas of the extremities.
HISTORY
The 79-year-old patient was admitted with recurring fever, weight loss, night sweat, a decrease in physical capacity and hematomas of the extremities.
FINDINGS
The patient presented with pancytopenia, elevated CRP and impaired renal function. A splenomegaly was evident in abdominal sonography. A bone marrow aspiration was performed.
DIAGNOSIS
Histopathologic examination revealed a visceral Leishmaniasis. The diagnosis was confirmed by PCR from peripheral blood.
THERAPY AND COURSE
After initiation of liposomal amphotericin B haematopoiesis recovered and CRP decreased. Initially the renal function deteriorated with prolongated improvement in the course of therapy.
CONCLUSIONS
Pancytopenia and corresponding symptoms are suspect for visceral Leishmaniasis also in patients supposed to be immunocompetent with travel history of endemic regions.
Topics: Aged; Antiprotozoal Agents; Diagnosis, Differential; Fever; Humans; Leishmaniasis, Visceral; Pancytopenia; Splenomegaly
PubMed: 35100643
DOI: 10.1055/a-1685-5173