Chronic Myeloid Leukemia Patients in Prolonged Remission following Interferon-alpha Monotherapy Have Distinct Cytokine and Oligoclonal Lymphocyte Profile

Peer reviewe

Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT), but in the control bone marrow aspirate (before ASCT) a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy

Infectious complications of induction treatment for acute myeloid leukaemia using the "7 + 3" protocol without antibiotic prophylaxis - 15 years of experience of one clinical site

Background. Infectious complications during induction chemotherapy of acute myeloid leukaemia are very common. Prophylactic use of antibiotics however is an ongoing challenge in this situation due to bacterial multi-drug resistance. The aim of this study was to provide a comprehensive overview of the incidence of infectious complications in patients with AML undergoing induction therapy using the "7+3" protocol without routine antibiotic prophylaxis at one clinical site providing specialised haematological care in the Czech Republic, over a period of 15 years. The study also evaluates the aetiological spectrum of causative agents and the development of antibiotic resistance in the context of the use of the various classes of antibiotics. The analysis includes evaluation of the importance of risk factors for infectious complications and their impact on treatment of the underlying disease. The data are compared with published figures for similar cohorts of patients. Patients and Methods. This study presents a retrospective analysis of infectious complications in 242 patients with acute myeloid leukaemia undergoing the first cycle of induction therapy without routine antibiotic prophylaxis in one clinical site in Czech Republic during years 2006-2020. Results. A total of 363 febrile episodes (FE) were recorded. At least 1 FE during the induction was detected in 229 (94.6%) patients. Clinically defined infection was the cause in 96 (26.4%) FEs and blood stream infection in 69 (19.0%) FEs. Both complications occurred simultaneously in 29 (8.0%) FEs. 169 (46.6%) FEs were evaluated as fever of unknown origin (FUO). The achievement of complete remission had a significant effect on the duration of the FE (6 vs. 9 days, P=0.0005) and on the overall survival duration (79.3 vs. 6.5 months, P<0.0001). Patients diagnosed with infection or FUO at diagnosis were significantly more likely to suffer from colonisation by multi-drug resistant bacterial strains at discharge (29.2% vs. 16.3%, P=0.022). This group of patients used antibiotic therapy for a significantly longer time (35 vs. 23 days, P<0.0001). Infection was a contributing cause of death in 18 (7.4%) patients. Mortality was significantly related to the failure to achieve complete remission (P<0.0001). Conclusion. Infectious mortality during induction treatment without routine antibiotic prophylaxis was comparable to the published cohorts with prophylaxis. Regular microbiology surveillance with adequate initial antibiotic treatment can compensate routine antibiotic prophylaxis with slower development of antibiotic resistance

Value of infliximab (Remicade®) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group

Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade®) is an anti-tumor necrosis factor alpha chimeric antibody that is used in the treatment of patients with rheumatoid arthritis or Crohn’s disease. Forty-six patients with myelodysplastic syndromes and a relatively low risk of developing acute leukemia were included in a randomized phase II study assessing the therapeutic activity of two dosages of infliximab administration (3 mg/kg vs. 5 mg/kg). The primary end point was the response rate. Responses were observed in 3 of 22 patients (13.1%) randomized to the 3 mg/kg arm, versus 0 of 21 patients randomized in the 5 mg/kg arm. According to the statistical design of the current study, neither of the two infliximab dose schedules tested showed sufficient activity as a single agent in this cohort of unselected patients with early myelodysplastic syndrome

Molecular Characterization of <b>β</b>-Thalassemia in the Czech and Slovak Populations: Mediterranean, Asian and Unique Mutations

<p>β-Thalassemia (β-thal) is considered rare in Central Europe. As in other malaria-free regions, the presence of β-thal in Central Europe reflects historical and recent immigration, and demographic changes that have influenced the genetic variability of the current populations living in this area. This study assesses the frequency and spectrum of mutations on the β-globin gene in Czech and Slovak subjects with clinical symptoms of thalassemia. The results of the initial part of this research were published more than two decades ago; the aim of this study was to update these original reports. During the period from 2002 to 2015, 400 cases from Czech and Slovak hematological centers were analyzed. Twenty-nine β-thal mutations, identified in 356 heterozygotes from 218 unrelated families, involve five unique mutations including a recently described insertion of a transposable L1 element into the β-globin gene. One mutation described here is reported for the first time. Most of the mutations were of Mediterranean origin and accounted for 82.0% of cases. All but one case studied were heterozygous carriers, manifesting β-thal minor, with rare exceptions represented by the rare (β⁰) codons 46/47 (+G) (<i>HBB</i>: c.142_142dupG) mutation associated with an α-globin gene quadruplication and by dominantly inherited β-thal with a more severe phenotype. One double heterozygous β-thal patient was a recent immigrant from Moldavia. The list of δβ-thal alleles (26 carriers, 16 families) contains Hb Lepore and two types of δβ⁰-thal deletions. In the past, genetic drift and migration as well as recent immigrations were responsible for the introduction of Mediterranean alleles, while several mutations described in single families were of local origin.</p

High-Dose Therapy and Autologous Stem-Cell Transplantation in Waldenstrom Macroglobulinemia:The Lymphoma Working Party of the European Group for Blood and Marrow Transplantation

International audiencePURPOSE: The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome. PATIENTS AND METHODS: We analyzed 158 adult patients with WM reported to the European Group for Blood and Marrow Transplantation (EBMT) between January 1991 and December 2005. Median time from diagnosis to ASCT was 1.7 years (range, 0.3 to 20.3 years), 32% of the patients experienced treatment failure with at least three lines of therapy, and 93% had sensitive disease at the time of ASCT. Conditioning regimen was total-body irradiation-based in 45 patients. Median follow-up for surviving patients was 4.2 years (range, 0.5 to 14.8 years). RESULTS: Nonrelapse mortality was 3.8% at 1 year. Ten patients developed a secondary malignancy, with a cumulative incidence of 8.4% at 5 years. Relapse rate was 52.1% at 5 years. Progression-free survival (PFS) and overall survival were 39.7% and 68.5%, respectively, at 5 years and were significantly influenced by number of lines of therapy and chemorefractoriness at ASCT. The achievement of a negative immunofixation after ASCT had a positive impact on PFS after ASCT. When used as consolidation at first response, ASCT provided a PFS of 44% at 5 years. CONCLUSION: ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy