No abstract

Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1(mut) and IDH2(mut) were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2(mut) was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1(mut) (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1(mut) or IDH2(mut) vs. IDH(neg). IDH1(mut) and IDH2(mut) were associated differently with NPM1(mut); co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDH(neg) (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.

Acquired hemophilia A (AHA) is a rare severe autoimmune bleeding disorder with significant morbidity and mortality. Although critical for disease control, there is no consensus for the best immunosuppressive regimen. Most authors use steroids first line, followed by other agents for steroid failures. Upfront combined regimens offer the advantage of reduced steroid-exposure and toxicity as well as increased efficacy. We retrospectively analyzed data from 32 AHA patients treated on an identical institutional such protocol: 1000 mg cyclophosphamide on day 1 and 22, 40 mg dexamethasone on day 1, 8, 15 and 22, and 100 mg rituximab on day 1, 8, 15 and 22 (the regimen was termed CyDRi). All patients received at least 1 cycle of CyDRi. If necessary, CyDRi was repeated until remission, no sooner than day 43 of the previous cycle. Bleeding control was rapidly achieved. The median time for bleeding control was 15.5 days (range 0-429, IQR 2.5-29.5). 31/32 (96.8%) of patients achieved durable CR. 29/32 patients (90.6%) were alive at last follow up, all of them in CR. The median time to reach first CR was 77 days (range 14-939; IQR 31-115). Toxicity and side effects were acceptable and milder than commonly used, prolonged steroid therapies. In conclusion, the CyDRi regimen produced markedly higher complete remission rates and overall survival than currently used sequential regimens. Taken together, CyDRi proved to be an attractive option for the immunosuppression of elderly AHA patients.

Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim of our study was to investigate the frequency of FLT3-ITD mutations followed by a detailed analysis of the mutational load and size of ITD insertions in a cohort consisting of 324 patients younger than 60 years old and treated with curative intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free survival (DFS). We observed worse OS and DFS for patients with high mutational load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038, respectively). In multivariate analyses, patients with FLT3-ITD(48-60bp) showed worse OS and DFS compared to other groups (FLT3-ITD(neg), FLT3-ITD (< 48b), FLT3-ITD (> 60bp); p = 0.014, p = 0.019, respectively). Our novel observation suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions (48-60 bp) represented an adverse prognostic subgroup of patients with AML.

Relapse is the main cause of treatment failure following hematopoietic stem cell transplantation for blastic phase chronic myeloid leukemia. Treatment options including donor lymphocyte infusion, second transplantation, interferon- and re-induction chemotherapy are often unsuccessful. We report a patient with blastic phase chronic myeloid leukemia relapsing after allogeneic stem cell transplantation. The post-transplant leukemia was characterized with B-lymphoid markers and multiple genetic abnormalities including double Ph-chromosomes. The disease was treated with three courses of salvage chemotherapy combined with donor lymphocyte infusion and bcr-abl tyrosine kinase inhibitor. The leukemia proved to be non-responsive both to immune therapy and STI 571. The presented case demonstrates the need for combination approaches in post-transplant relapsed leukemia and discusses the possible contributing mechanisms of STI-571 resistance.