Endoscopic diagnosis of a colonic localisation of a mantle cell lymphoma.

Extra-nodal localisations of mantle cell lymphomas are most frequently found in the gastrointestinal tract. It is therefore important for an endoscopist to be familiar with the endoscopic image of a mantle cell lymphoma. In this case series of three patients with colonic involvement of mantle cell lymphoma, we discuss the endoscopic diagnosis.

Targeted next-generation sequencing using a multigene panel in myeloid neoplasms: Implementation in clinical diagnostics.

INTRODUCTION: Detection of mutations in patients with myeloid neoplasms (MNs) has shown great potential for diagnostic and prognostic purposes. Next-generation sequencing (NGS) is currently implemented for the diagnostic profiling of the four major MN subgroups. METHODS: First, we validated the targeted NGS approach using the TruSight Myeloid panel. Next, we screened 287 patients with a clinical suspicion of MN and 61 follow-up patients with documented MN. RESULTS: Validation of the NGS workflow resulted in maximal precision, accuracy, sensitivity, and specificity for gene variants with an allele frequency of at least 5% and a minimal read depth of 300. In our diagnostic screen, we identified at least one somatic mutation in 89% of patients with proven MN. Of the 155 newly diagnosed MN cases, 126 (81%) showed at least one mutation, confirming clonality. Moreover, the co-occurrence of mutated genes in the different MN subentities facilitates their classification and justifies the diagnostic use of a pan-myeloid panel. Furthermore, several of these mutations provide additional prognostic information independently of traditional prognostic scoring systems. CONCLUSION: Pan-myeloid targeted NGS fits elegantly in the routine diagnostic approach of MNs allowing for an improved diagnosis, subclassification, and prognosis.

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.

Management of myelodysplastic syndromes in adults: guidelines from the Belgian Haematological Society.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of haematological disorders characterized by ineffective haematopoiesis and an increased risk for leukemic transformation. In recent years several new therapeutics have emerged that have demonstrated to alter the natural course of the disease. This document summarizes the state of the art in diagnosis and treatment of this heterogeneous disease, as proposed by a group of expert haematologists in the field of MDS from the Belgian Haematological Society. Its main purpose is to guide clinicians in daily practice to treat patients with this disease, within the limitations of current reimbursement modalities in Belgium.

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium.

The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.

The Belgian 2010 consensus recommendations for the treatment of multiple myeloma.

Since the introduction of novel therapeutic agents including thalidomide, lenalidomide and bortezomib, the prognosis of multiple myeloma (MM) has significantly improved. These agents have been incorporated into numerous treatment schedules for newly diagnosed as well as more advanced MM patients. Hence, the therapeutic options for MM have become more complex and subject to rapid changes. The multiple myeloma study group (MMSG) of the Belgian Hematological Society has established recommendations for the treatment of MM as based on an extensive review of the literature which is also summarized in this paper. The recommendations are the result of a consensus opinion between haematologists with experience in the field and representing most haematology centres in Belgium. Where applicable, reimbursement criteria are also taken into account. The consensus recommendations should be a reference for use by clinical haematologists in daily practice.

Rituximab in auto-immune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study.

OBJECTIVES: For better characterizing the effect of anti-CD20 therapy, we analysed the use of rituximab in Belgian patients experiencing auto-immune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP). DESIGN: We performed a retrospective multicentric analysis of patients with AIHA and ITP treated with rituximab in Belgium. SETTING: Haematological departments were invited to fill in a questionnaire about patient and disease characteristics. SUBJECTS: All patients with AIHA and ITP, both primary and secondary to other diseases, who received one or more courses of rituximab during their disease course were included. Sixty-eight courses of rituximab in 53 patients with AIHA and 43 courses in 40 patients with ITP were analyzed. INTERVENTION: Response rates, duration of response and factors predictive for response were assessed. RESULTS: All patients were given rituximab after failing at least one previous line of treatment, including splenectomy in 19% and 72.5% of AIHA-patients and ITP-patients respectively. Overall response rates were 79.2% in AIHA and 70% in ITP, with a median follow-up since first rituximab administration of 15 months (range 0.5-62) in AIHA and 11 months (range 0-74) in ITP. Progression free survival at 1 and 2 years were 72% and 56% in AIHA and 70% and 44% in ITP. In this retrospective analysis we were not able to identify pretreatment characteristics predictive for response to rituximab. Nine patients with AIHA and three patients with ITP were given one or more additional courses of rituximab. Most of these patients, who had responded to a previous course, experienced a new response comparable to the previous one, both in terms of quality and of duration of response. Finally, the outcome of patients who failed to respond to rituximab therapy was poor both in terms of response to subsequent therapy and in terms of survival. CONCLUSIONS: This study confirms that rituximab induces responses in a majority of previously treated patients with AIHA and ITP. Response duration generally exceeds 1 year. Retreatment with rituximab in responding patients is most often successful. The outcome of patients who fail on rituximab is poor. We were not able to identify pretreatment patient characteristics predicting for response.

Successful patching of iatrogenic rupture of the fetal membranes.

Rupture of the fetal membranes is a common, but potentially serious complication of invasive fetal procedures. Quintero described a technique to seal the fetal membrane defect by means of a bloodpatch, usually called 'amniopatch' in this application. The successful use in two consecutive patients with ruptured membranes after a fetoscopic intervention at respectively 17 and 22 weeks' gestational age is described, together with a literature review of published experience.