AimTo assess the benefit of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) regimen as a first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL) presenting with unfavorable or aggressive features, and autologous stem cell transplantation (ASCT) as a part of the first-line treatment for selected DLBCL patients with additional aggressive features.MethodsWe retrospectively analyzed 75 newly diagnosed DLBCL patients with Ki-67+≥80% or International Prognostic Index ≥2 who were treated with R-DA-EPOCH between 2005 and 2015. Of 24 DLBCL patients with additional aggressive features (Ki-67+≥90% or age-adjusted IPI≥2) who were planned to receive consolidation with ASCT, 17 patients underwent the procedure. We determined the overall response rate (ORR), complete remission (CR), partial remission (PR), 5-year overall survival (OS), and progression free survival (PFS) in all DLBCL patients and specifically those planned to receive ASCT.ResultsAll 75 patients included in the analysis started one or more cycles of therapy. The ORR, CR, and PR rates were 80%, 55%, and 25%, respectively. The response was non-evaluable in 10 of 75 patients due to treatment discontinuation. The OS and PFS rates for all 75 patients were 70% and 61%, respectively, and 80% and 79%, respectively, for 24 planned-to-receive-ASCT patients. Age (≤65 vs >65 years) had no prognostic impact on OS and PFS (P = 0.994 and P = 0.827, respectively).ConclusionOur retrospective analysis of one of the largest DLBCL patient cohorts outside the US National Cancer Institute showed that R-DA-EPOCH is a very effective therapeutic option as a first-line treatment of DLBCL patients with unfavorable prognostic features irrespective of their age. ASCT provided additional benefit for DLBCL patients with additional aggressive features.

Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph- MPNs), and elevated mean-platelet-volume (MPV) is a common finding in these diseases. The clinical and prognostic significances of MPV in patients with primary (PMF) and secondary myelofibrosis (SMF) have not been reported. We retrospectively analyzed 87 patients with myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was recorded in addition to other hematological and clinical parameters. MPV was elevated in both PMF and SMF patients in comparison to controls, whereas there was no statistically significant difference between PMF and SMF. Elevated MPV was associated with lower platelets (P = 0.016), higher white blood cells (P = 0.015), higher percentage of circulatory blasts (P = 0.009), higher lactate dehydrogenase (P = 0.011), larger spleen size (P = 0.014) and higher Dynamic International Prognostic score category (P = 0.027), while there was no statistically significant association with driver mutations or degree of bone marrow fibrosis. Higher MPV was univariately associated with inferior overall survival in the whole cohort (HR = 3.82, P = 0.006), PMF (HR = 4.35, P = 0.007) and SMF patients (HR = 7.22, P = 0.034). These associations remained significant in multivariate analyses adjusted for DIPSS. Higher MPV is associated with more aggressive disease features and exhibits powerful independent prognostic properties in both PMF and SMF settings.

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Conflict of interest statementThe authors declare that there are no conflicts of interest. AcknowledgementsThe authors would like to thank Wilma Miletić for help with manuscript preparation. 2 AbstractObjectives: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS.Methods: 36 newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene.Results: Mutations were present in 11 out of 36 patients (31%), which was not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (p=0.039) and lower TIBC (p=0.018). Ferritin was found to be higher for the untransfused mutated patients (p=0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (p=0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival (OS) in addition to a poorer leukemia free survival (LFS) (p=0.004 and p=0.003, respectively). Discussion:The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anaemia.The effect of mutations on survival could be mediated by changes in iron metabolism. Conclusion:The HFE gentopye may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy.