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Pellegrino Musto,1 Vittorio Simeon,2 Roberto Guariglia,3 Gabriella Bianchino,4 Vitina Grieco,4 Filomena Nozza,4 Francesco La Rocca,2 Gioacchino Marziano,1 Anna Vittoria Lalinga,5 Emiliano Fabiani,6 Maria Teresa Voso,6 Patrizia Scaravaglio,7 Cristina Mecucci,8 Giovanni D'Arena31Scientific Direction, 2Laboratory of Preclinical and Translational Research, 3Unit of Hematology and Stem Cell Transplantation, 4Laboratory of Clinical Research and Advanced Diagnostics, 5Pathology Unit, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; 6Department of Hematology, Universita Cattolica del Sacro Cuore, Rome, Italy; 7Laboratory of Internal Medicine and Hematology, S Luigi Gonzaga Hospital, Orbassano, Italy; 8Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, ItalyAbstract: The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing – from a clinical, pathological, and biological point of view – for at least some of these patients as a potential distinct entity is discussed.Keywords: myelodysplastic syndromes, myeloproliferative neoplasms, lenalidomide, del(5q), JAK2, World Health Organization

Pellegrino Musto,1 Vittorio Simeon,2 Roberto Guariglia,3 Gabriella Bianchino,4 Vitina Grieco,4 Filomena Nozza,4 Francesco La Rocca,2 Gioacchino Marziano,1 Anna Vittoria Lalinga,5 Emiliano Fabiani,6 Maria Teresa Voso,6 Patrizia Scaravaglio,7 Cristina Mecucci,8 Giovanni D'Arena31Scientific Direction, 2Laboratory of Preclinical and Translational Research, 3Unit of Hematology and Stem Cell Transplantation, 4Laboratory of Clinical Research and Advanced Diagnostics, 5Pathology Unit, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; 6Department of Hematology, Universita Cattolica del Sacro Cuore, Rome, Italy; 7Laboratory of Internal Medicine and Hematology, S Luigi Gonzaga Hospital, Orbassano, Italy; 8Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, ItalyAbstract: The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing – from a clinical, pathological, and biological point of view – for at least some of these patients as a potential distinct entity is discussed.Keywords: myelodysplastic syndromes, myeloproliferative neoplasms, lenalidomide, del(5q), JAK2, World Health Organization

Summary Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375–2500 mg) for a median of 11 months (range 0·4–75). Eight patients (16%) showed grade 2–3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709 μg/l at baseline to 1100 μg/l after 12 months of treatment (P = 0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3 months, median overall survival was 37·5 months. The results of this first survey of DFX in HR-MDS are comparable, in terms of safety and efficacy, with those observed in lower-risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR-MDS patients.