Oreste Villani

Azacitidine for the treatment of lower risk myelodysplastic syndromes : a retrospective study of 74 patients enrolled in an Italian named patient program.

Azacitidine induces responses and prolongs overall survival compared with conventional care regimens in patients who have high‐risk myelodysplastic syndromes (MDS). However, limited data are available concerning the efficacy and safety of azacitidine in patients who have lower risk MDS.

Rituximab for warm‐type idiopathic autoimmune hemolytic anemia: a retrospective study of 11 adult patients

Warm‐type idiopathic autoimmune hemolytic anemia (AIHA) is a relatively common hematologic disorder resulting from autoantibody production against red blood cells. Steroids represent the first‐line therapeutic option, and immunosuppressive agents as well as splenectomy are used for refractory cases. Recently, the anti‐CD20 monoclonal antibody rituximab has been shown to control autoimmune hemolysis in patients with refractory chronic disease. We report results from a retrospective analysis of 11 adult patients receiving rituximab for steroid‐refractory AIHA of the warm type at a mean age of 55 yr (range 23–81 yr). All patients were given methyl‐prednisolone as first‐line treatment and some of them also received azathioprine and intravenous high‐dose immunoglobulins. One patient underwent splenectomy. All patients were considered refractory to steroids and/or immunosuppressive drugs and all were then given weekly rituximab (375 mg/m2) for four consecutive weeks. An increase in hemoglobin (Hgb) levels in response to rituximab, with a mean increment of 3.3 g/dL (95% CI 2.1–4.4), was observed in all cases. Four patients required packed red cell transfusions before starting rituximab and all became transfusion‐free. At a mean follow‐up of 604 d (range 30–2884 d) since the treatment of AIHA with rituximab, all patients are alive, eight (73%) of them in complete remission (CR) and three (27%) in partial remission (PR). A moderate hemolysis still persisted in six (54%) patients. In conclusion, our experience clearly demonstrates that anti‐CD20 monoclonal antibody rituximab is an effective and safe alternative treatment option for idiopathic AIHA, in particular, for steroid‐refractory disease.

Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: A brief review

Iron overload is a frequent consequence in transfusion-dependent myelodysplastic syndromes (MDSs), which often requires iron chelation therapy (ICT). Interestingly, ICT may sometimes induce a hematologic improvement that leads to significant reduction or complete interruption of blood transfusions. This phenomenon has been recently described in MDS treated with the new oral chelator deferasirox. Here we briefly review the literature about this phenomenon and discuss the possible biological mechanisms underlying hematologic effects of deferasirox in MDS, starting from a new paradigmatic case in whom both hemoglobin level and platelet count improved, inducing transfusion-independence, soon after starting the treatment with deferasirox.

Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study

A prospective, multicenter, randomized trial comparing pamidronate administration (60–90 mg once a month for 1 year) versus simple observation in 177 patients with asymptomatic myeloma was performed to explore whether the administration of this drug reduces the rate of and/or the time to progression to overt, symptomatic disease. No relevant side effects were recorded in pamidronate-treated patients. With a minimum follow-up of 5 years for live patients, there were 56/89 (62.9%) progressions in the pamidronate-treated group and 55/88 (62.5%) within the controls (p = NS). Median time to progression was 46 and 48 months, respectively (p = NS). Overall survival was also similar between the two groups. Skeletal-related events at the time of progression were observed in 40/55 (72.7%) controls, but only in 22/56 (39.2%) pamidronate-treated patients (p = 0.009). In conclusion, the administration of pamidronate in asymptomatic myeloma, while reducing bone involvement at progression, did not decrease the risk of transformation and the time to progression into overt myeloma.

Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party

BACKGROUND The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. PATIENTS AND METHODS Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. RESULTS An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction. CONCLUSION Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.

Salvage therapy with lenalidomide and dexamethasone in relapsed primary plasma cell leukemia.

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Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia.

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A shorter time to the first treatment may be predicted by the absolute number of regulatory T-cells in patients with Rai stage 0 chronic lymphocytic leukemia†

Regulatory T-cells (Tregs) are increased in chronic lymphocytic leukemia(CLL) and correlates with clinical and biological features of active/progressive disease. However, little is known about their ability to predict the time to first treatment (TFT). We evaluated 75 patients with Rai stage 0 CLL, in whom the absolute number of Tregs was determined at diagnosis, and correlated to main clinical and biological features, as well as to the need of receiving any specific therapy during the course of the disease. After a median follow-up of 30 months, 12 patients(16%) required therapy at some time from the diagnosis. Treated patients showed a significant higher number of peripheral white blood cells and B-lymphocytes, platelet count, cases with unmutated immunoglobulin heavy chain status, and high-risk cytogenetic abnormalities,as well as lower hemoglobin values, than patients who did not need therapy. A greater number of circulating Tregs was detected in treated patients (P < 0.001). Multivariate analysis confirmed that the absolute number of Tregs was an independent predictor of TFT in these patients, the best predictive cut-off being 41/mL. These data show that the absolute Tregs cell number is able to identify Rai stage 0 CLL patients at higher risk of requiring therapy.

Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes

This was a retrospective, comparative study focused on the extended follow-up of 192 transfusion-dependent patients with myelodysplastic syndromes treated (n. 83) or not treated (n. 109) with recombinant erythropoietin alpha (r-EPO) as single agent during the course of their disease. The results supported the safety of this treatment in the long term and also showed a significant survival advantage (median 52 months vs. 31 months, p<0.0095) in responding patients as compared to non-responding ones or to subjects never treated with r-EPO. At multivariate analysis, response to r-EPO maintained an independent prognostic value on OS.

No cross-resistance after sequential use of romiplostim and eltrombopag in chronic immune thrombocytopenic purpura

To the editor: Romiplostim and eltrombopag (a synthetic fusion peptibody and a nonpeptide molecule, respectively) are second-generation thrombopoietin mimetics/agonists that are structurally dissimilar to thrombopoietin and do not induce the formation of autoantibodies.[1][1][⇓][2]–[3][3] They