Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes.

Transfusion dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions. Transfusion dependency is associated with leukemic progression and shorter survival. Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76, and median age at diagnosis of MDS was 74. Patients had received an average of 13.4 ± 7.6 RBC units in the past 4 months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1,550 μg/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of International Prognostic Scoring System (IPSS), French-American-British (FAB), and/or World Health Organization (WHO) status, though chelated patients had received more RBC transfusions (p = 0.014). Iron chelation therapy may be underutilized in transfusion-dependent patients. Undertreatment can be reduced by complementing sound clinical judgment with the generally accepted guidelines of a serum ferritin level >1,000 μg/L and/or two or more RBC transfusions per month for the past year; considering patients on the basis of their IPSS, FAB, and/or WHO status; and individually tailored treatment regimens. Prospective randomized trials are necessary to establish causally the efficacy of iron chelation therapy in MDS

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey

OBJECTIVES: We evaluated azacitidine (Vidaza(®)) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. METHODS: This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. RESULTS: The median age of patients was 74·7 (range: 43·9-87·8) years; 69·4% had MDS, 26·5% had primary or secondary AML, and 4·1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67·3%, 28·6%, and 18·4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n = 29), 41·4% had CR, PR, or HI, 41·4% had SD, and 17·2% had TF. Among AML patients (n = 9), 44·4% had CR or PR, 33·3% had SD, and 22·2% had TF. TI was observed in 14/32 (43·8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0·571 (0·422-0·696). CONCLUSIONS: Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy

Myelofibrosis patients in Belgium : disease characteristics

Objective: To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to predefined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies. Methods: A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative. Results: A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≥ 50 000/μl and 201 (80%) had platelet count ≥ 100 000/μl. Of 250 patients, 85 (34%) had a myeloblast count ≥ 1%. Six (2%) patients had undergone a splenectomy. Thirteen (5.2%) patients had undergone radiotherapy for splenomegaly. Conclusions: The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development

Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients wih lower risk myelodysplastic syndromes

Background: Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of ironoverload and associated organ damage, and death. Emerging evidence indicates that iron chelation ther-apy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especiallythose classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1).Methods: Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centersin Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). Results: Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 g/L. Of the 80chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox followingdeferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patientschelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiacmortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1years for non-chelated patients (p < 0.001). For patients chelated ≥6 m or patients classified as adequatelychelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusionintensity (HR = 1.08, p = 0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m(HR = 0.24, p < 0.001). Conclusion: Six or more months of adequate ICT is associated with markedly better overall survival. Thissuggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS