[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.
[Show abstract][Hide abstract] ABSTRACT: Background
Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of iron overload and associated organ damage, and death. Emerging evidence indicates that iron chelation therapy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especially those classified as IPSS Low or Intermediate-1 (Low/Int-1).
Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centers in Belgium. Statistical analysis stratified by duration (>6 vs. <6 months) and quality of chelation (adequate vs. weak).
Crude chelation rate was 63% but 88% among patients with serum ferritin >1000 μg/L. Of the 80 chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox following deferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patients chelated >6 m, and 30% among patients chelated adequately; with a trend towards reduced cardiac mortality in chelated patients. Overall, median OS was 10.2 years for chelated and 3.1 years for non-chelated patients (p < 0.001). For patients chelated >6 m or patients classified as adequately chelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusion intensity (HR = 1.08, p = 0.04) but was lower in patients receiving adequate chelation or chelation >6 m (HR = 0.24, p < 0.001).
Six or more months of adequate ICT is associated with markedly better overall survival. This suggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS.
No preview · Article · May 2014 · Leukemia research
[Show abstract][Hide abstract] ABSTRACT: Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.
Full-text · Article · Feb 2014 · Journal of the National Cancer Institute
[Show abstract][Hide abstract] ABSTRACT: We report on a 36-year-old man who presented to the emergency department with haemoptysis. Computed tomography (CT) of the thorax showed a pulmonary mass paramediastinal in the right upper lobe, with the density of a haematoma. Laboratory data demonstrated an absolute lymphocytosis of 5.900 × 10/l (normal range, 1.150-3.250 × 10/l) and a prolonged activated partial thromboplastin time (APTT) of 47.7 s (normal range, 28.0-39.0 s). A de novo diagnosis of lymphoplasmacytic lymphoma (Waldenström macroglobulinaemia) was made, complicated by an acquired von Willebrand syndrome (aVWS) as demonstrated by further laboratory investigations. In this case report, we present a case of aVWS with markedly prolonged APTT and haemoptysis that revealed an underlying Waldenström macroglobulinaemia.
No preview · Article · Jan 2014 · Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis
[Show abstract][Hide abstract] ABSTRACT: Here, we report the case of a 57-year-old man, who was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). His diagnostic workup identified a translocation t(3;9)(p13;p13). This is the fifth case reported to date that involved the forkhead box P1 gene (FOXP1) and paired box gene 5 (PAX5). The PAX5-FOXP1 translocation is a nonrandom aberration, which is recurrent in both childhood and in adult B-ALL, and may contribute to leukemogenesis by blocking differentiation of hematopoietic cells into mature B-cells.
[Show abstract][Hide abstract] ABSTRACT: Bronchiolitis Obliterans Organizing Pneumonia (BOOP) can complicate allogeneic haematopoietic stem cell transplantation. It is associated with prior graft-versus-host disease (GVHD) and the case fatality is 21%. In 22%, diagnosis is preceded by tapering the corticosteroids given as a treatment for GVHD. We report a fatal case of BOOP after tapering the corticosteroids that the patient received for a Pneumocystis jirovecii pneumonia after stem cell transplantation.
No preview · Article · May 2010 · Acta clinica Belgica