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Data derived from clinical trials consistently show a prolongation of overall survival of late-stage MDS patients with the introduction of azacytidine. Nevertheless, the applicability of the above results to real-world clinical settings may be questionable due to the strict design, the controlled medical environment, and the limited patient sample of explanatory studies. We retrospectively compared the outcome of two well-balanced groups of late-stage MDS patients. The first consisted of 46 patients treated with azacytidine (AZA cohort) and the second of 41 patients treated with other agents (non-AZA cohort). Patients in the AZA cohort displayed superior survival compared to the non-AZA ones. However, subgroup analysis revealed that azacytidine conferred a significant survival advantage only in patients with AML-MDS and those who attained a CR at any time after treatment initiation, while all other patients displayed comparable outcome with the non-AZA cohort. Larger series are needed to determine which patients benefit most from azacytidine therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Myelodysplastic syndrome (MDS) patients with renal impairment (RI) were not assessed in the approval trials of 5-azacytidine, thus the optimal use of 5-azacytidine in such patients is currently undefined. We retrospectively analyzed 42 IPSS intermediate-2 and high-risk patients with moderate, mild or no RI undergoing 5-azacytidine therapy in a non-trial setting. We demonstrate that patients in all three groups achieved comparable responses and had similar overall and event-free survival. Likewise, both treatment toxicity and dose adjustments were not significantly influenced by renal function status. A transient but reversible decline in glomerular filtration rate was observed in patients either with or without RI, without affecting the therapeutic schedule. Our results provide the first evidence that 5-azacytidine is effective and well-tolerated in patients with mild and moderate RI and, if confirmed by prospective randomized studies, advocate that such patients can be managed in an analogous fashion to patients with normal renal function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Telomere exhaustion and increased telomerase activity are associated with the acquisition of aggressive molecular events in a variety of haematological malignancies. In Philadelphia chromosome negative myeloproliferative neoplasms (Ph(neg)MPN's), telomere dynamics during clonal evolution of these diseases have not yet been fully elucidated. Herein we demonstrated that telomere shortening is a global phenomenon in Ph(neg)MPN's, irrespective of disease phenotype, treatment administration and JAK2V617F mutational status but the presence of additional cytogenetic abnormalities further affects them. Consistent with the above finding, TA was upregulated in CD34+ haemopoietic progenitors from almost all Ph(neg)MPN subgroups compared to healthy donors. Moreover, TL below the cut-off value of 27% could predict disease progression in Ph(neg)MPN patients (PFS at 5 years 39% vs 81%). Thus, TL emerges as a new prognostic marker in Ph(neg)MPN, reflecting probably the genetic instability of highly proliferating MPN clones., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The recently proposed, ISSWM staging system for symptomatic patients with WM was based on patients treated with alkylating agents and nucleoside analogs and has not been externally validated nor has been validated for cause-specific survival (CSS). We independently validated ISSWM both for overall survival (OS) and for CSS and assessed whether addition of elevated serum LDH may add to the strength of ISSWM in 335 patients treated upfront mainly with alkylating agents (43%), and rituximab-based therapies (47%). ISSWM could discriminate three groups with significantly different OS and CSS (p<0.01 for both). High serum LDH was predictive of shorter OS and CSS (p<0.01). The combination of high risk according to ISSWM and elevated serum LDH identified a subset of patients for whom innovative treatment approaches are needed., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)