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Patients with AAT are often initially misdiagnosed as having immune thrombocytopenia (ITP) but do not usually respond to ITP first-line therapy (i.e. corticosteroids [CS] and intravenous immunoglobulin [IVIg]). After a median follow-up of 4.0 years (range: 1.2-11.9), two (16.7%) patients developed AA (7 and 41.5 months after AAT diagnosis), and two developed B-cell lymphoma (8 and 9 years after AAT diagnosis). Acquired amegakaryocytic thrombocytopenia and red cell aplasia in a patient with thymoma progressing to aplastic anemia successfully treated with allogenic stem cell transplantation. Amegakaryocytic thrombocytopenia is characterized by severe thrombocytopenia associated with aplastic or hypoplastic megakaryocytic lineage in the bone marrow (BM), and usually preserved granular and erythroid lineage. [Extracted from the article]

Background: Hairy cell leukemia (HCL) is a rare chronic B cell malignancy, characterized by infiltration of bone marrow, blood and spleen by typical "hairy cells" that bear the BRAFV600E mutation. However, in addition to the intrinsic activation of the MAP kinase pathway as a consequence of the BRAFV600E mutation, the potential participation of other signaling pathways to the pathophysiology of the disease remains unclear as the precise origin of the malignant hairy B cells. Materials and methods: Using mRNA gene expression profiling based on the Nanostring technology and the analysis of 290 genes with crucial roles in B cell lymphomas, we defined a 17 gene expression signature specific for HCL. Results: Separate analysis of samples from classical and variant forms of hairy cell leukemia showed almost similar mRNA expression profiles apart from overexpression in vHCL of the immune checkpoints CD274 and PDCD1LG2 and underexpression of FAS. Our results point to a post-germinal memory B cell origin and in some samples to the activation of the non-canonical NF-κB pathway. Conclusions: This study provides a better understanding of the pathogenesis of HCL and describes new and potential targets for treatment approaches and guidance for studies in the molecular mechanisms of HCL. [ABSTRACT FROM AUTHOR]

They rather identified six Ph+AML patients harboring I NPM1 i mutations and outlined some criteria, in which I NPM1 i mutation, to discriminate Ph+AML from BP-CML. Subsequently, using the oncomine myeloid research assay panel of ThermoFisher Scientific SP ® sp (3% sensitivity for point mutations and 5% for indels), the NGS analysis singled out the I NPM1 i type A mutation with variant allele frequency at 42-6% on the diagnostic bone marrow sample. Does eventually NPM1 mutation in blast phase chronic myeloid leukemia (BP-CML) exist? The prognostic value of a I NPM1 i mutation in BP-CML and Ph+AML cannot be determined because of the scantiness of case reports. [Extracted from the article]

Objectives: To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. Methods: Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary end-points were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. Results: Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. Conclusion: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload. [ABSTRACT FROM AUTHOR]

Marrow cells from patients with higher-risk myelodysplastic syndrome ( MDS) exhibit constitutive nuclear factor ( NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m2, days 1, 4, 8 and 11) and low dose cytarabine arabinoside ( LDAC; 10 mg/m2, then 20 mg/m2 from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response ( CR, n = 1), marrow- CR ( n = 3), partial response ( PR, n = 5) and haematological improvement ( HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients ( P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow- CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes. [ABSTRACT FROM AUTHOR]