Imatinib-Induced Bone Marrow Aplasia in Chronic Myelogenous Leukemia.

Imatinib is a tyrosine kinase inhibitor (TKI) and is a commonly used medication for treatment of chronic myelogenous leukemia (CML). Aplastic anemia is a very uncommon complication of Gleevec, and only a few cases are reported in the literature. We present a case of a 63-year-old Asian female who was initiated on imatinib for treatment of CML with good response in cell counts. Four months after Gleevec initiation, the patient was admitted to the hospital with extreme fatigue and noted to have severe pancytopenia. Patient received multiple blood transfusions. Finally, the patient underwent bone marrow biopsy, which showed concern for aplastic anemia with marked hypocellular bone marrow. Gleevec was held, blood counts were monitored, and supportive care was given. Patient had slow recovery of her blood counts. There remains scarcity of data on this topic and no criteria exist to predict the myelosuppression with TKI therapy. Our case report aims to reemphasize the need for increased research on myelosuppression with TKI therapy.

A Case of Severe Aplastic Anemia in a 35-Year-Old Male With a Good Response to Immunosuppressive Therapy.

Aplastic anemia (AA) is a severe but rare hematologic condition associated with hematopoietic failure leading to decreased or total absent hematopoietic precursor cells in the bone marrow. AA presents at any age with equal distribution among gender and race. There are three known mechanisms of AA: direct injuries, immune-mediated disease, and bone marrow failure. The most common etiology of AA is considered to be idiopathic. Patients usually present with non-specific findings, such as easy fatigability, dyspnea on exertion, pallor, and mucosal bleeding. The primary treatment of AA is to remove the offending agent. In patients in whom the reversible cause was not found, patient management depends on age, disease severity, and donor availability. Here, we present a case of a 35-year-old male who presented to the emergency room with profuse bleeding after a deep dental cleaning. He was found to have pancytopenia on his laboratory panel and had an excellent response to immunosuppressive therapy.

[Hypoplastic acute promyelocytic leukemia with continuous hypocellular bone marrow after remission].

An 87-year old female presented with unsteady gait and occasional subcutaneous hematomas. Blood examination findings revealed pancytopenia and mild coagulopathy. Both the histopathological evaluation of bone marrow smears and bone marrow biopsy revealed a hypocellular bone marrow. However, APL cells were observed and PML-RARA fusion gene was detected. On the basis of these findings, the patient was diagnosed with hypoplastic acute promyelocytic leukemia. She received ATRA treatment and achieved complete remission (CR) 29 days from the commencement of therapy. After the first CR, she received two courses of ATO as a consolidation therapy. Following the latter treatments, she maintained CR, but a hypoplastic bone marrow was still observed. Hypoplastic AML is defined as AML with a low bone marrow cellularity. It is clinically important to distinguish it from aplastic anemia and hypoplastic MDS. It has been suggested that both cytogenetic and morphological diagnosis are imperative to the differential diagnosis of hypocellular bone marrow.

Missing Cells: Pathophysiology, Diagnosis, and Management of (Pan)Cytopenia in Childhood.

Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings, such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia, whereas antibody-mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. By contrast, pancytopenia is frequently associated with a hypocellular bone marrow, and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita, and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition, and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC) can reliably be differentiated on a morphological level, the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC, and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pan)cytopenia, their pathophysiology, characteristic bone marrow findings, and therapeutic approaches.

Bone marrow hypocellularity does not affect tolerance or efficacy of azacitidine in patients with higher-risk myelodysplastic syndromes.

The efficacy and tolerance of azacitidine in higher-risk myelodysplasia with hypocellular bone marrow (BM) are unknown. This post hoc AZA-001 trial analysis assessed whether baseline BM cellularity affected the overall survival (OS) advantage demonstrated with azacitidine versus conventional care regimens (CCR). Baseline BM biopsies of <30% cellularity were considered hypocellular with data evaluable from 299 patients (azacitidine n = 154, CCR n = 145); 13% (n = 39) hypocellular, 87% (n = 260) non-hypocellular. Patient characteristics were balanced between cellularity and treatment groups. Most patients (90-100%) had 2-3 cytopenias at baseline. Median (range) azacitidine treatment cycle lengths were 35·5 (28-54) and 33·0 (15-75) d in hypocellular and non-hypocellular groups, respectively. At 33 months, median OS was not reached (NR) [95% confidence interval (CI): 19·2, NR] in hypocellular patients receiving azacitidine versus 16·9 months (95% CI: 11·1, 19·3) with CCR (P = 0·001); and in non-hypocellular patients, it was 21·1 months (95% CI: 16·2, 34·7) versus 15·3 months (95% CI: 9·3, 17·6) (P = 0·012). Azacitidine tolerance was similar regardless of cellularity. Grade 3-4 thrombocytopenia and neutropenia occurred similarly in hypocellular patients treated with azacitidine versus CCR (80% vs. 92% and 88% vs. 75%). Azacitidine OS results are consistent with those from AZA-001, regardless of cellularity, and demonstrate its safety and efficacy in higher-risk myelodysplasia with hypocellular BM.

Lower segment cesarean section in a patient with severe thrombocytopenia and pregnancy induced hypertension.

Thrombocytopenia in pregnancy carries a major risk of feto-maternal morbidity and mortality. We present a case of hypocellular bone marrow with severe thrombocytopenia with pregnancy induced hypertension (PIH) for emergency lower segment cesarean section (LSCS). This disease is characterized by pancytopenia and hypocellular bone marrow with impaired morphology and maturation. Causes of death due to this disease include hemorrhage and infection secondary to thrombocytopenia and neutropenia especially following surgery. We report successful management of emergency LSCS with severe thrombocytopenia with severe PIH.