5-Azacitidine efficacy and safety in patients aged >65 years with myelodysplastic syndromes outside clinical trials
Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy. Leukemia & lymphoma
(Impact Factor: 2.89).
02/2012; 53(8):1558-60. DOI: 10.3109/10428194.2012.660632
The efficacy and safety of azacitidine in elderly patients (aged >65 years) with myelodysplastic syndromes (MDS) treated outside clinical trials are reported. Thirty-eight patients with MDS received azacitidine (75 mg/m(2), schedule 5+2 +2): seven patients were classified as having refractory cytopenia with multilineage dysplasia (RCMD), nine patients with refractory anemia with excess of blasts (RAEB) type 1, 18 patients with RAEB type 2 and four patients with chronic myelomonocytic leukemia type 2 (CMML-2). According to International Working Group (IWG) 2006 criteria, after the first four cycles we detected complete remission in seven patients (CR, 18%), improvement of bone marrow dysplasia and reduction of blast percentage in seven patients (partial response, 18%), stable disease in 20 patients (53%) and progression to acute leukemia in four patients (10%). Median overall survival for all patients treated was 16.4 months. Only mild non-hematologic toxicity was detected (grade 1-2 nausea and pruritus), whereas 55% of patients experienced hematologic side effects (25% grade 3-4 thrombocytopenia and 30% grade 3-4 neutropenia). Our results suggest that advanced age should not preclude effective treatment with azacitidine in non-selected elderly patients wih MDS.
Available from: Yishai Ofran
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ABSTRACT: Hypomethylating agents have become the standard therapy for patients with high-risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA-treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high-risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29-92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 10(9) /L and neutrophil count below 0.5 × 10(9) /L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
American Journal of Hematology 02/2013; 88(2). DOI:10.1002/ajh.23368 · 3.80 Impact Factor
Annals of Hematology 03/2013; 92(10). DOI:10.1007/s00277-013-1732-2 · 2.63 Impact Factor
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ABSTRACT: Abstract The tolerability of azacitidine (AZA) allows its administration in elderly patients. The objective of this study was to analyze the clinical and biological characteristics, transfusion independence (TI), overall survival (OS) and toxicity of a series of 107 patients ≥75 years of age from the Spanish Registry of myelodysplastic syndromes (MDS) treated with AZA. The median age (range) was 78 (75-90) years. According to the WHO classification 86/102 (84%) were MDS, 10/102 (10%) mixed myeloproferative/myelodysplastic, and 6/102 (6%) were acute myeloblastic leukemia. Regarding MDS by the International Prognostic System score on initiation of AZA 38/84 (45%) were low-intermediate-1 risk and 46/84 (55%) were intermediate-2-high risk. Ninety-five patients (89%) were red blood cell or platelet transfusion dependent. The AZA schedule was 5-0-0 in 39/106 (37%) patients, 5-2-2 in 36/106 (34%) patients, and 7 consecutive days in 31/106 (29%) patients. The median number of cycles administered was 8 (range, 1-30). Thirty eight out of 94 (40%) patients achieved TI. Median OS (95%CI) was significantly better in patients achieving TI (n=38) compared to patients that did not (n=56) (22 [20.1, 23.9] months vs. 11.1 [4.8, 17.5] months, p=.001). No significant differences were observed in TI rate and OS among the three different schedules. With a median follow-up of 14 [min-max, 1-50] months, the median OS (95%CI) of the 107 patients was 18 (12-23) months and the probability of OS (95%CI) at 2 years was 34% (22%-46%). Cycles were delayed in 31/106 (29%) patients and 47/101 patients (47%) were hospitalized for infection. These results show that treatment with AZA was feasible and effective in this elderly population, with 40% achieving TI, having a better OS than patients not achieving it. The schedule of AZA administration did not affect efficacy and toxicity.
Leukemia & lymphoma 08/2013; 55(6). DOI:10.3109/10428194.2013.834532 · 2.89 Impact Factor
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