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Blood Jun 2023Biallelic germ line excision repair cross-complementing 6 like 2 (ERCC6L2) variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies,...
Biallelic germ line excision repair cross-complementing 6 like 2 (ERCC6L2) variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies, characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germ line variants collected retrospectively from 11 centers globally, with a follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). The subjects presented with 19 different variants of ERCC6L2, and we identified a founder mutation, c.1424delT, in Finnish patients. The median age of the subjects at baseline was 18 years (range, 2-65 years). Changes in the complete blood count were mild despite severe bone marrow (BM) hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without HMs. Signs of progressive disease included increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in the BM morphology. The median age at the onset of HM was 37.0 years (95% CI, 31.5-42.5; range, 12-65 years). The overall survival (OS) at 3 years was 95% (95% CI, 85-100) and 19% (95% CI, 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome with a 3-year OS of 28% (95% CI, 0-61). Our results demonstrated the importance of early recognition and active surveillance in patients with biallelic germ line ERCC6L2 variants.
Topics: Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Retrospective Studies; Bone Marrow Failure Disorders; Leukemia, Myeloid, Acute; Anemia, Aplastic; DNA Repair; Pancytopenia; Acute Disease; DNA Helicases
PubMed: 36952636
DOI: 10.1182/blood.2022019425 -
Lancet (London, England) Jun 2023
Topics: Humans; Pancytopenia; Anorexia Nervosa; Bone Marrow; Lung Abscess
PubMed: 37270240
DOI: 10.1016/S0140-6736(23)00857-7 -
Blood Oct 2020Clonal hematopoiesis (CH) is common in older persons and is associated with an increased risk of hematologic cancer. Here, we review studies establishing an association... (Review)
Review
Clonal hematopoiesis (CH) is common in older persons and is associated with an increased risk of hematologic cancer. Here, we review studies establishing an association between CH and hematopoietic malignancy, discuss features of CH that are predictive of leukemic progression, and explore the role of hematopoietic stressors in the evolution of CH to acute myeloid leukemia or myelodysplastic syndrome. CH due to point mutations or structural variants such as copy-number alterations is associated with an ∼10-fold increased risk of hematopoietic malignancy. Although the absolute risk of hematopoietic malignancy is low, certain features of CH may confer a higher risk of transformation, including the presence of TP53 or spliceosome gene mutations, a variant allele fraction >10%, the presence of multiple mutations, and altered red blood indices. CH in the setting of peripheral blood cytopenias carries a very high risk of progression to a myeloid malignancy and merits close observation. There is emerging evidence suggesting that hematopoietic stressors contribute to both the development of CH and progression to hematopoietic malignancy. Specifically, there is evidence that genotoxic stress from chemotherapy or radiation therapy, ribosome biogenesis stress, and possibly inflammation may increase the risk of transformation from CH to a myeloid malignancy. Models that incorporate features of CH along with an assessment of hematopoietic stressors may eventually help predict and prevent the development of hematopoietic malignancies.
Topics: Animals; Antineoplastic Agents; Biomarkers; Cell Transformation, Neoplastic; Clonal Evolution; Clonal Hematopoiesis; Disease Susceptibility; Genetic Predisposition to Disease; Hematologic Neoplasms; Hematopoiesis; Humans; Mutation; Neoplasms, Second Primary; Pancytopenia; Stress, Physiological
PubMed: 32736382
DOI: 10.1182/blood.2019000991 -
Expert Review of Hematology Feb 2021: Pregnancy-associated aplastic anemia (pAA) occurs when aplastic anemia (AA) is diagnosed for the first time during pregnancy and it is a rare but serious condition... (Review)
Review
: Pregnancy-associated aplastic anemia (pAA) occurs when aplastic anemia (AA) is diagnosed for the first time during pregnancy and it is a rare but serious condition leading to severe maternal and fetal complications. It is unknown whether pregnancy triggers bone marrow failure or if this state is unrelated to the pathogenesis of pAA.: In this review, three new cases of pAA are presented and its controversial etiologic relationship with pregnancy, its atypical presentation, and management are also discussed. Furthermore, a literature review of pAA cases between 1975 and 2020 was performed in PubMed, accessed via the National Library of Medicine PubMed interface. Keywords included 'aplastic anemia' AND 'pregnancy'. We found 54 cases reported in the literature with a clear diagnosis of pAA.: The diagnosis of pAA is challenging since pregnancy is associated with physiologic hematological changes in the complete blood count which can mask the disease. Meticulous monitoring and adequate support therapy given by a trained multidisciplinary team have the potential to improve outcomes for women and their neonates. All women should receive frequent assessments to optimize their care during pregnancy and after delivery, definitive treatment should be offered.
Topics: Anemia, Aplastic; Blood Cell Count; Female; Humans; Infant, Newborn; Pancytopenia; Pregnancy; United States
PubMed: 33430674
DOI: 10.1080/17474086.2021.1875816 -
Hematology (Amsterdam, Netherlands) Dec 2019Pancytopenia is a frequent entity in clinical practice as a feature of a myriad of conditions, ranging from benign to malignant diseases. Since the cause of pancytopenia... (Review)
Review
BACKGROUND
Pancytopenia is a frequent entity in clinical practice as a feature of a myriad of conditions, ranging from benign to malignant diseases. Since the cause of pancytopenia depends on environmental factors, it is important to know the common etiologies of pancytopenia, however, few studies address this.
OBJECTIVES
To identify the etiology of pancytopenia in our population and compare them with what is reported elsewhere.
METHODS
We conducted an observational study of patients with pancytopenia in a Mexican Tertiary Care Center. Clinical, hematological and bone marrow studies were performed in all patients.
RESULTS
Of 109 cases included, the mean age at diagnosis was 49.4 years, with a slightly higher female incidence (53.2%). The most common causes of pancytopenia were: MDS (20.2%), megaloblastic anemia (18.3%) and AML (12.8%).
DISCUSSION
We found a complex picture of pancytopenia in Mexico and compared it with what is reported elsewhere in the literature.
CONCLUSION
The sociocultural context in which the patients develop helps narrowing the possible etiology of pancytopenia, and therefore hasten the diagnostic process. Of all the studies available, bone marrow aspiration seems the most useful.
Topics: Adolescent; Adult; Age of Onset; Aged; Aged, 80 and over; Female; Humans; Male; Mexico; Middle Aged; Pancytopenia; Sex Factors; Tertiary Care Centers
PubMed: 30890036
DOI: 10.1080/16078454.2019.1590961 -
Zhonghua Yi Xue Za Zhi Mar 2022As an independent disease, aplastic anemia (AA) has been recognized for more than a century. When AA is diagnosed, other non-AA bone marrow failures should be excluded....
As an independent disease, aplastic anemia (AA) has been recognized for more than a century. When AA is diagnosed, other non-AA bone marrow failures should be excluded. It is termed as exclusive diagnosis of AA. The exclusive diagnosis of AA is helplessly based on that there is no parameter by which AA can be sensitively and specifically diagnosed now. So further searching for the meaningful diagnostic parameters of AA should be carried on to establish a direct diagnostic protocol of this disease and make it possible to differentiate it clearly from other bone marrow failure disease such as congenenital bone marrow failure, hypoplastic myelodysplastic syndromes, AA-paroxysmal nocturnal hemoglobinuria syndromes, large granules lymphocyte leukemia, clonal cytopenia of undetermined significance, immunorelated pancytopenia, acute hemopoietic arresting and idiopathic cytopenia of undetermined significance. The new markers and technologies being helpful for distinguishing AA from other bone marrow failures should be used in diagnosing AA. Correct understanding and application of exclusive diagnosis is not only related to the correctness of diagnosis and treatment of excluded diseases, but also to the quality of AA diagnosis, treatment and research.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Hemoglobinuria, Paroxysmal; Humans; Myelodysplastic Syndromes; Pancytopenia
PubMed: 35330574
DOI: 10.3760/cma.j.cn112137-20211207-02728 -
Journal of Investigative Medicine High... 2021We report a rare case of a 32-year-old male who ingested 32.4 to 54 mg of colchicine and presented after 44 hours. He developed progressive multiple organ failure with...
We report a rare case of a 32-year-old male who ingested 32.4 to 54 mg of colchicine and presented after 44 hours. He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis. He also developed electrolyte abnormalities and refractory hypoglycemia. Initial treatment consisted of activated charcoal, fluids, and broad-spectrum antibiotics with supportive treatment of mechanical ventilation, hemodialysis, vasopressors, N-acetylcysteine, colony-stimulating factors, and blood products. Literature shows potential benefit of colchicine-specific Fab fragments for acute toxicity with limited studies and is not currently available in the United States. Further research for N-acetylcysteine protocol for acute liver failure in colchicine toxicity and potential use of colchicine-specific Fab fragments is needed. Our case demonstrates the importance of early use of activated charcoal for ingestion overdose with the incorporation of poison control into multidisciplinary team for coordinated patient care.
Topics: Acute Kidney Injury; Adult; Colchicine; Drug Overdose; Humans; Male; Multiple Organ Failure; Pancytopenia
PubMed: 34229452
DOI: 10.1177/23247096211029744 -
The American Journal of Emergency... Sep 2021As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) pandemic progresses, various hematologic complications have emerged, often centered around the...
As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) pandemic progresses, various hematologic complications have emerged, often centered around the hypercoagulable state. However, pancytopenia represents a rare but serious complication from SARS-CoV2 infection. While lymphopenia is a common finding, concomitant acute anemia and thrombocytopenia are not commonly reported. We describe a novel case of SARS-CoV2 pancytopenia in a 40-year-old male without active risk factors for cell line derangements but subsequent critical illness.
Topics: Acute Kidney Injury; Adult; COVID-19; Continuous Renal Replacement Therapy; Humans; Male; Pancytopenia; Respiration, Artificial; Respiratory Insufficiency; SARS-CoV-2
PubMed: 33653644
DOI: 10.1016/j.ajem.2021.02.043 -
Rheumatology International May 2024Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus... (Review)
Review
Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.
Topics: Humans; Anemia, Aplastic; Pancytopenia; Lupus Erythematosus, Systemic; Cyclosporine; Cyclophosphamide
PubMed: 38512478
DOI: 10.1007/s00296-024-05585-6 -
Tzu Chi Medical Journal 2022The causes of pancytopenia vary in different populations depending on age, gender, nutrition, geographic location, standard of living, and exposure to certain infections...
OBJECTIVE
The causes of pancytopenia vary in different populations depending on age, gender, nutrition, geographic location, standard of living, and exposure to certain infections and drugs. As the severity of pancytopenia and its underlying etiology determine the management and prognosis, identifying the correct etiology in a given case is crucial and helps in implementing timely and appropriate treatment. The objectives of this study were to study the clinical profile and hematological parameters of pancytopenic adults and to identify different etiologies of pancytopenia. This observational study was conducted in the Medicine department of a tertiary care teaching hospital.
MATERIALS AND METHODS
The study was conducted on 100 adult patients aged 18-65 years presenting with pancytopenia. All the participants were subjected to detailed clinical examination and relevant investigations including bone marrow (BM) examination. Categorical variables were presented in number and percentage (%). Qualitative variables were correlated using the Chi-square test. A =0.05 was considered statistically significant.
RESULTS
A female preponderance was observed, and the majority of patients were aged between 18 and 40 years. The most common clinical features were generalized weakness, fever, and pallor. Seventy-four percent of patients were vegetarians; 58% had vitamin B12 deficiency, 25% had folic acid deficiency and 19% had a deficiency of both. The most common cause of pancytopenia was megaloblastic anemia (MA) (37%), followed by dimorphic anemia (DA) (26%), aplastic anemia (AA) (20%), and hematological malignancies (11%).
CONCLUSION
MA, DA, and AA are the most prevalent etiologies of pancytopenia. BM examination is of utmost importance in the definitive diagnosis of pancytopenia and is useful in initiating timely treatment as a significant number of causes of pancytopenia are potentially curable.
PubMed: 35233363
DOI: 10.4103/tcmj.tcmj_17_21