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Henk M Lokhorst,
Bronno van der Holt,
Jan J Cornelissen,
Marie-José Kersten,
Marinus van Oers,
Reinier Raymakers,
Monique C Minnema,
Sonja Zweegman,
Jeroen J Janssen,
Mark Zijlmans,
Gerard Bos,
Nicolaas Schaap,
Shulamiet Wittebol, Okke de Weerdt,
Rianne Ammerlaan,
Pieter Sonneveld
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ABSTRACT: To prospectively evaluate allogeneic stem cell transplantation (allo-SCT) for myeloma as part of first-line therapy, a donor versus no-donor analysis was performed of patients treated in the HOVON-50 study, a study that was originally designed to examine thalidomide combined with intensive therapy. Two hundred sixty patients having received an autologous-SCT fulfilled the criteria to be included, 138 patients without an HLA-identical sibling donor and 122 patients with a donor. After a median follow-up of 77 months, complete remission, progression-free survival (PFS), and overall survival were not significantly different between the 2 groups. PFS at 6 years was 28% for patients with a donor versus 22% for patients without a donor (P = .19) and overall survival at 6 years from high-dose melphalan was 55%, irrespective of having a donor (P = .68). Cumulative incidence of nonrelapse mortality at 6 years after autologous-SCT was 16% in the donor group versus 3% in the no-donor group (P < .001). However, PFS was significantly prolonged in the 99 patients who actually proceeded to allo-SCT compared with the 115 patients who continued maintenance or received a second high-dose melphalan, but the difference did not translate into a prolonged survival benefit. These results do not support a general application of allo-SCT in all myeloma patients as part of first-line therapy.
Blood 03/2012; 119(26):6219-25; quiz 6399. · 9.90 Impact Factor
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Lieke H van der Helm,
Canan Alhan,
Pierre W Wijermans,
Marinus van Marwijk Kooy,
Ron Schaafsma,
Bart J Biemond,
Aart Beeker,
Mels Hoogendoorn,
Bastiaan P van Rees, Okke de Weerdt, [......],
Monique C Minnema,
Rolf E Brouwer,
Fransien Croon-de Boer,
Matthijs Eefting,
Kon-Siong G Jie,
Arjan A van de Loosdrecht,
Jan Koedam,
Nic J G M Veeger,
Edo Vellenga,
Gerwin Huls
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ABSTRACT: The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified.
British Journal of Haematology 12/2011; 155(5):599-606. · 4.94 Impact Factor
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Henk M Lokhorst,
Ingo Schmidt-Wolf,
Pieter Sonneveld,
Bronno van der Holt,
Hans Martin,
Rene Barge,
Uta Bertsch,
Jana Schlenzka,
Gerard M J Bos,
Sandra Croockewit, [......],
Harm Sinnige,
Igor Blau,
Michel Delforge,
Gregor Verhoef, Okke de Weerdt,
Pierre Wijermans,
Shulamiet Wittebol,
Ulrich Duersen,
Edo Vellenga,
Hartmut Goldschmidt
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ABSTRACT: In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001). Complete remission (CR) and very good partial remission (VGPR) were also higher after TAD. After High Dose melphalan 200mg/m(2) response was comparable in both arms, 76% and 79% respectively. However, CR plus VGPR were significantly higher in the patients randomized to TAD (49% vs. 32%, p<0.001). CTC grade 3-4 adverse events were similar in both arms.
Haematologica 01/2008; 93(1):124-7. · 6.42 Impact Factor
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ABSTRACT: The t(2;11)(q37;q23) is a rare recurrent cytogenetic abnormality associated with de novo and therapy-related acute myeloid leukemia, resulting in a MLL-SEPT2 fusion gene. We report on a case of therapy-related acute myeloid leukemia M2 showing a t(2;11)(q37;q23) and resulting in a new subtype of a MLL-SEPT2 chimeric transcript. The literature on this translocation is reviewed.
Cancer Genetics and Cytogenetics 08/2007; 176(1):72-5. · 1.39 Impact Factor
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ABSTRACT: In vitro statins induce apoptosis in myeloma and lymphoma cells in a dose-and time-dependent way. In combination with dexamethasone and doxorubicin, statins have a chemo-sensitizing effect. Twenty-eight patients with relapsed myeloma or lymphoma were treated with a dose-escalating regimen of simvastatin for 7 days followed by VAD in myeloma patients and CHOP in lymphoma patients. The maximum tolerated dose was 15 mg/kg/day simvastatin. The most frequently reported side-effects were fatigue, gastrointestinal CTC grade 1-2 and neutropenic fever. The dose-limiting toxicity was neutropenic sepsis and grade 3 gastrointestinal side effects. High-dose simvastatin given immediately prior to chemotherapy is safe and tolerable up to a dose of 15 mg/kg/day.
Haematologica 05/2006; 91(4):542-5. · 6.42 Impact Factor
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ABSTRACT: Background: Multiple myeloma is an incurable disease and after several lines of chemotherapy, patients enter a phase in which no standard treatment options are available. The poor outlook of these patients requires mild, palliative therapy with low toxicity. Previously used regimens either require frequent hospital attendance, lack efficacy or have significant toxicity.Methods: In the current study, daily low dose, oral cyclophosphamide (100 mg) and prednisone (10–20 mg; CP) were administered to patients with advanced myeloma. Forty-two patients with progressive disease after melphalan-based and VAD treatment were enrolled.Results: Objective responses were observed in 29 of 42 (69%) patients. In responding patients, median overall survival and progression-free survival were 22.2 months and 15.0 months, respectively. In non-responders, median OS was 3.5 months only. Side-effects were limited. Cytopenia was the most frequent event (8/29) prompting dose reduction. CP had to be stopped permanently in four patients (two cytopenia, two infections).Conclusion: Orally administered, low dose continuous CP is a feasible, effective and well-tolerated regimen in the management of advanced multiple myeloma.
The Netherlands Journal of Medicine 59(2):50-56. · 2.07 Impact Factor
