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Blood Aug 2022Inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure, usually in association with ≥1 extrahematopoietic...
Inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure, usually in association with ≥1 extrahematopoietic abnormalities. BM failure, which can involve ≥1 cell lineages, often presents in the pediatric age group. Furthermore, some children initially labeled as having idiopathic aplastic anemia or myelodysplasia represent cryptic cases of inherited BM failure. Significant advances in the genetics of these syndromes have been made, identifying more than 100 disease genes, giving insights into normal hematopoiesis and how it is disrupted in patients with BM failure. They have also provided important information on fundamental biological pathways, including DNA repair: Fanconi anemia (FA) genes; telomere maintenance: dyskeratosis congenita (DC) genes; and ribosome biogenesis: Shwachman-Diamond syndrome and Diamond-Blackfan anemia genes. In addition, because these disorders are usually associated with extrahematopoietic abnormalities and increased risk of cancer, they have provided insights into human development and cancer. In the clinic, genetic tests stemming from the recent advances facilitate diagnosis, especially when clinical features are insufficient to accurately classify a disorder. Hematopoietic stem cell transplantation using fludarabine-based protocols has significantly improved outcomes, particularly in patients with FA or DC. Management of some other complications, such as cancer, remains a challenge. Recent studies have suggested the possibility of new and potentially more efficacious therapies, including a renewed focus on hematopoietic gene therapy and drugs [transforming growth factor-β inhibitors for FA and PAPD5, a human poly(A) polymerase, inhibitors for DC] that target disease-specific defects.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Dyskeratosis Congenita; Humans; Neoplasms; Pancytopenia
PubMed: 35605178
DOI: 10.1182/blood.2020006481 -
British Journal of Haematology Mar 2024Pancytopenia with hypocellular bone marrow is the hallmark of aplastic anaemia (AA) and the diagnosis is confirmed after careful evaluation, following exclusion of...
Pancytopenia with hypocellular bone marrow is the hallmark of aplastic anaemia (AA) and the diagnosis is confirmed after careful evaluation, following exclusion of alternate diagnosis including hypoplastic myelodysplastic syndromes. Emerging use of molecular cyto-genomics is helpful in delineating immune mediated AA from inherited bone marrow failures (IBMF). Camitta criteria is used to assess disease severity, which along with age and availability of human leucocyte antigen compatible donor are determinants for therapeutic decisions. Supportive care with blood and platelet transfusion support, along with anti-microbial prophylaxis and prompt management of opportunistic infections remain key throughout the disease course. The standard first-line treatment for newly diagnosed acquired severe/very severe AA patients is horse anti-thymocyte globulin and ciclosporin-based immunosuppressive therapy (IST) with eltrombopag or allogeneic haemopoietic stem cell transplant (HSCT) from a matched sibling donor. Unrelated donor HSCT in adults should be considered after lack of response to IST, and up front for young adults with severe infections and a readily available matched unrelated donor. Management of IBMF, AA in pregnancy and in elderly require special attention. In view of the rarity of AA and complexity of management, appropriate discussion in multidisciplinary meetings and involvement of expert centres is strongly recommended to improve patient outcomes.
Topics: Young Adult; Humans; Aged; Anemia, Aplastic; Immunosuppressive Agents; Cyclosporine; Hematopoietic Stem Cell Transplantation; Bone Marrow Failure Disorders; Unrelated Donors; Pancytopenia; Hematology
PubMed: 38247114
DOI: 10.1111/bjh.19236 -
Blood Apr 2023The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely,...
The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter. For model development, patients were labeled as having acquired or inherited BMF depending on their genomic data. Data sets were unbiasedly clustered, and an ensemble model was trained with cases from the largest cluster of a training cohort (n = 359) and validated with an independent cohort (n = 127). Cluster A, the largest group, was mostly immune or inherited aplastic anemia, whereas cluster B comprised underrepresented BMF phenotypes and was not included in the next step of data modeling because of a small sample size. The ensemble cluster A-specific model was accurate (89%) to predict BMF etiology, correctly predicting inherited and likely immune BMF in 79% and 92% of cases, respectively. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment.
Topics: Humans; Bone Marrow Diseases; Diagnosis, Differential; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia
PubMed: 36542832
DOI: 10.1182/blood.2022017518 -
International Journal of Hematology Mar 2024Acquired aplastic anemia (AA) in children is a rare bone marrow failure that requires several special considerations for its diagnosis and treatment compared with that... (Review)
Review
Acquired aplastic anemia (AA) in children is a rare bone marrow failure that requires several special considerations for its diagnosis and treatment compared with that in adults. The most common issue is the differential diagnosis with refractory cytopenia of childhood and inherited bone marrow failure syndromes, which is crucial for making decisions on the appropriate treatment for pediatric AA. In addition to detailed morphological evaluation, a comprehensive diagnostic work-up that includes genetic analysis using next-generation sequencing will play an increasingly important role in identifying the underlying etiology of pediatric AA. When discussing treatment strategies for children with acquired AA, the long-term sequelae and level of hematopoietic recovery that affect daily or school life should also be considered, although the overall survival rate has reached 90% after immunosuppressive therapy or hematopoietic cell transplantation (HCT). Recent advances in HCT for pediatric patients with acquired AA have been remarkable, with the successful use of upfront bone marrow transplantation from a matched unrelated donor, unrelated cord blood transplantation or haploidentical HCT as salvage treatment, and fludarabine/melphalan-based conditioning regimens. This review discusses current clinical practices in the diagnosis and treatment of acquired AA in children based on the latest data.
Topics: Adult; Child; Humans; Anemia, Aplastic; Bone Marrow Transplantation; Hematopoietic Stem Cell Transplantation; Pancytopenia; Immunosuppression Therapy; Transplantation Conditioning
PubMed: 36867357
DOI: 10.1007/s12185-023-03564-4 -
The Primary Care Companion For CNS... Sep 2022
Topics: Cannabis; Hallucinogens; Humans; Pancytopenia
PubMed: 36084655
DOI: 10.4088/PCC.21cr03155 -
American Journal of Therapeutics
Topics: Humans; Leflunomide; Pancytopenia; Antirheumatic Agents; Methotrexate
PubMed: 35404332
DOI: 10.1097/MJT.0000000000001497 -
Acta Neurologica Belgica Aug 2023
Topics: Humans; Levetiracetam; Pancytopenia; Anticonvulsants; Piracetam
PubMed: 36344882
DOI: 10.1007/s13760-022-02138-1 -
JAMA Feb 2020
Topics: Adolescent; Bone Marrow; Career Choice; Female; Humans; Medical Oncology; Pancytopenia
PubMed: 32044946
DOI: 10.1001/jama.2020.0252 -
The Journal of the Association of... Apr 2022Current study intends to study the etiological profile of Pancytopenia and to identify the complete blood count (CBC), peripheral smear (PS) findings which are helpful... (Observational Study)
Observational Study
UNLABELLED
Current study intends to study the etiological profile of Pancytopenia and to identify the complete blood count (CBC), peripheral smear (PS) findings which are helpful in narrowing the differential diagnosis and in planning the additional investigations to arrive at a specific diagnosis.
MATERIAL
Hospital based observational study being conducted at tertiary centre, Jaipur.
INCLUSION CRITERIA
Patients >18 years, CBC on admission fulfilling criteria of pancytopenia as mentioned in definition.
EXCLUSION CRITERIA
Patients > 80 years, Patients on radiotherapy and chemotherapy., Observation :Mean age of patients was 35.42 years with majority (29.90%) patients with majority of patients were in 2nd and 3r decade of their life with male preponderance Male: female ratio is 1.15:1). Vitamin B-12 deficiency (34.02%), folate deficiency (18.55%) CLD (9.27%) were the most common cause of pancytopenia.
CONCLUSION
Detailed clinical history and meticulous physical examination along with baseline hematological investigations, provides invaluable information in the complete workup of pancytopenic patients, helping in systematic planning of further investigations to diagnose and ascertain the cause.
Topics: Adult; Blood Cell Count; Diagnosis, Differential; Female; Folic Acid Deficiency; Humans; Male; Pancytopenia; Vitamin B 12 Deficiency
PubMed: 35443537
DOI: No ID Found