5-azacitidine efficacy and safety in patients aged >65 years with myelodysplastic syndromes outside clinical trials.
ABSTRACT 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.
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ABSTRACT: of key recommendations Diagnosis 1 Myelodysplastic syndrome (MDS) should be suspected in patients with otherwise unexplained cytopenias(s) or mac-rocytosis. Grade 1A 2 The initial assessment of a patient with unexplained cytopenias(s) may not confirm a diagnosis of MDS. Fur-ther follow-up and reassessment may be necessary to reach a firm diagnosis. Grade 2B,C 3 Initial assessment of a patient with suspected MDS should include a minimum set of investigations and the differen-tial diagnosis of marrow dysplasia should be considered. Grade 1A 4 Patients with MDS should be assessed by a haematologist and, except where clearly inappropriate, offered review by a regional or national expert given the disease rarity. 5 All cases of MDS should be classified according to the World Health Organization (WHO) Revised Classification 2008. Grade 1A 6 Bone marrow cytogenetic analysis should be performed on all patients with suspected MDS having a bone marrow examination. Grade 1A 7 Consideration should be given at diagnosis to the progno-sis for each individual patient, with application of the revised International Prognostic Scoring System (IPSS-R). Grade1B 8 All cases of MDS should be reported to the National Cancer Registry and MDS-specific registries if applicable.British Journal of Haematology 02/2014; 164(4):503-525. · 4.94 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; · 2.61 Impact Factor
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ABSTRACT: Introduction: Therapeutic strategies for elderly patients affected by myelodysplastic syndromes (MDS) are scarce and only few patients have an advantage in performing allogeneic bone marrow transplant. Area covered: Primary endpoints for treatment of elderly MDS patients were not curative, but rather allowing to maintain a good quality of life through prolongation of overall survival. In this context, azacitidine showed to improve responses in this subset of patients compared to conventional established regimens, such as intensive or low-dose chemotherapy and best supportive care. Good safety profile of the drug was reported either when it was used inside or outside clinical trials. Improved quality of response was observed when the drug was administered beyond the first response, and it is now usually recommended to continue it at the same dose and schedule in responding patients. Expert opinion: Evaluation of baseline prognostic factors and comorbidities may help to identify patients who can benefit from the prolonged administration of the drug. Real life data regarding efficacy and safety of azacitidine in MDS elderly patients are required in order to confirm the results of clinical trials.Expert Opinion on Pharmacotherapy 07/2014; · 2.86 Impact Factor