Marinus H J van Oers

Publications (58)475.73 Total impact

• Article: Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease.

  Daniel W Hommes, Marjolijn Duijvestein, Zuzana Zelinkova, Pieter C F Stokkers, Maartje Holsbergen-de Ley, Jaap Stoker, Carlijn Voermans, Marinus H J van Oers, Marie José Kersten
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  ABSTRACT: Although new therapeutic strategies have been developed to control Crohn's disease, medical treatment for refractory cases is not able to prevent extensive and/or repeat surgery. Recently, several cases have been reported of successful remission induction in Crohn's disease patients by means of hematopoietic stem cell transplantation (HSCT). Here we report our long-term (4 to 6 years) outcome in three patients. Three patients (two male, one female) with active severe Crohn's disease were planned to undergo autologous HSCT. All patients were intolerant or refractory to conventional therapies, including anti-TNFα antibodies. Patients either refused surgery or surgery was considered not to be a feasible alternative due to the extensive disease involvement of the small intestine. Peripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4 g/m(2), followed on day 4 by subcutaneous injections with G-CSF 5 μg/kg twice daily until leukapheresis. CD34+ cells were isolated after leukapheresis by magnetic cell sorting. In two of the three patients a second round of stem cell mobilization using G-CSF only was required, either because of low yield or because of insufficient recovery after CD34 selection. Prior to transplantation, immune ablation was achieved using cyclophosphamide 50mg/kg/day (4 days), antithymocyte globulin 30 mg/kg/day (3 days) and prednisolone 500 mg (3 days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed. All three patients successfully completed stem cell mobilization, and two of them subsequently underwent conditioning and autologous HSCT with CD34+ cell selection. Treatment was well tolerated, with acceptable toxicity. Now, 5 and 6 years post-transplantation, these patients are in remission under treatment. The third patient went into remission after mobilization and therefore she decided not to undergo conditioning and HSCT transplantation. After a successful pregnancy she relapsed two years later. Since then, she suffers from refractory Crohn's disease for which we are now reconsidering conditioning and transplantation. Autologous HSCT appears to be safe and can be an alternative strategy for Crohn's disease patients with severe and therapy resistant disease.
  Journal of Crohn s and Colitis 12/2011; 5(6):543-9. · 2.57 Impact Factor
• Article: Treatment strategies in advanced stage follicular lymphoma.

  Marinus H J van Oers, Marie José Kersten
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  ABSTRACT: Although the introduction of anti-CD20 monoclonal antibodies has improved the outcome of patients with follicular lymphoma, a curative treatment is still not available. Many questions still remain to be answered: when should treatment be initiated? Is there an optimal first line treatment and can this treatment be individualized on the basis of prognostic markers? What is the best treatment strategy for relapsed follicular lymphoma and what is the place of the many novel agents? Should maintenance treatment be given to all patients and how? In the present review we will address these questions.
  Best practice & research. Clinical haematology 06/2011; 24(2):187-201. · 3.13 Impact Factor
• Article: Reply to U. Duhrsen et al.

  Marinus H J van Oers, Evelyn Tönnissen, Martine Van Glabbeke, Livia Giurgea, Joop H Jansen, Richard Klasa, Robert E Marcus, Max Wolf, Eva Kimby, Andrej Vranovsky, Harald Holte, Anton Hagenbeek, Bert A van der Reijden
  Journal of Clinical Oncology 08/2010; · 18.37 Impact Factor
• Article: A case of ATRA-induced isolated myocarditis in the absence of circulating malignant cells: demonstration of the t(15;17) translocation in the inflammatory infiltrate by in situ hybridisation.

  Reinier H van Rijssel, Jurgen Wegman, Monique E Oud, Steven T Pals, Marinus H J van Oers
  Leukemia research 07/2010; 34(7):e142-4. · 2.36 Impact Factor
• Article: Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study.

  Marinus H J van Oers, Martine Van Glabbeke, Livia Giurgea, Richard Klasa, Robert E Marcus, Max Wolf, Eva Kimby, Mars van t Veer, Andrej Vranovsky, Harald Holte, Anton Hagenbeek
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  ABSTRACT: In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the maintenance phase was 33 months. Now, we report the long-term outcome of maintenance treatment, with a median follow-up of 6 years. Overall, 465 patients were randomly assigned to induction with either six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab plus CHOP (R-CHOP). Those in complete remission or partial remission after induction (n = 334) were randomly assigned to maintenance treatment with rituximab (375 mg/m(2) intravenously once every 3 months) or observation. Rituximab maintenance significantly improved progression-free survival (PFS) compared with observation (median, 3.7 years v 1.3 years; P < .001; hazard ratio [HR], 0.55), both after CHOP induction (P < .001; HR, 0.37) and R-CHOP (P = .003; HR, 0.69). The 5-year overall survival (OS) was 74% in the rituximab maintenance arm, and it was 64% in the observation arm (P = .07). After progression, a rituximab-containing salvage therapy was given to 59% of patients treated with CHOP followed by observation, compared with 26% after R-CHOP followed by rituximab maintenance. Rituximab maintenance was associated with a significant increase in grades 3 to 4 infections: 9.7% v 2.4% (P = .01). With long-term follow-up, we confirm the superior PFS with rituximab maintenance in relapsed/resistant FL. The improvement of OS did not reach statistical significance, possibly because of the unbalanced use of rituximab in post-protocol salvage treatment.
  Journal of Clinical Oncology 06/2010; 28(17):2853-8. · 18.37 Impact Factor
• Article: BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study.

  Marinus H J van Oers, Evelyn Tönnissen, Martine Van Glabbeke, Livia Giurgea, Joop H Jansen, Richard Klasa, Robert E Marcus, Max Wolf, Eva Kimby, Andrej Vranovsky, Harald Holte, Anton Hagenbeek, Bert A van der Reijden
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  ABSTRACT: The prognostic value of residual BCL2/immunoglobulin heavy chain (BCL2/IgH) -positive cells in peripheral blood (PB) or bone marrow (BM) after induction treatment in follicular lymphoma (FL) is still controversial. In a prospective randomized phase III intergroup trial of 465 patients with relapsed/resistant follicular lymphoma (FL), we showed that addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone induction results in increased overall and complete response rates, and that rituximab maintenance strongly improves median progression-free survival (PFS) as well as overall survival. Here, we studied whether BCL2/IgH major break point levels in PB/BM correlated with response rates/quality for the induction phase and PFS for the maintenance phase. Samples were obtained before and after induction therapy and at the end of the 2 years maintenance/observation period. BCL2/IgH major break point-positive cells were quantified by genomic quantitative polymerase chain reaction in 792 samples from 238 patients. Pretreatment BCL2/IgH levels had no significant prognostic value for overall response or complete remission rates after induction treatment, but pretreatment positive BM results had an adverse prognostic value for PFS from first randomization (P = .023). Importantly, BCL2/IgH levels at the end of induction treatment had no prognostic value for PFS from second randomization. The highly significant improved PFS by rituximab maintenance was observed in both BCL2/IgH PB/BM-positive and -negative groups. Postinduction BCL2/IgH major break point status in BM/PB is not useful for decisions on subsequent therapy for patients with relapsed/resistant FL.
  Journal of Clinical Oncology 04/2010; 28(13):2246-52. · 18.37 Impact Factor
• Article: Analysis of efficacy and prognostic factors of lenalidomide treatment as part of a Dutch compassionate use program.

  Evelien Kneppers, Henk M Lokhorst, Corien M Eeltink, Gerwin Huls, Marie José Kersten, Jan Koedam, Monique C Minnema, Marinus H J van Oers, Reinier A P Raymakers, Martijn R Schaafsma, Edo Vellenga, Pierre W Wijermans, Shulamiet Wittebol, Pieter Sonneveld, Sonja Zweegman
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  ABSTRACT: To obtain efficacy and safety data on lenalidomide treatment outside of clinical trials, we analyzed the clinical data of 114 patients with refractory or relapsed multiple myeloma treated with lenalidomide on a compassionate use basis. The recommended treatment consisted of lenalidomide 25 mg given on days 1-21 of a 28-day cycle, in combination with dexamethasone. A median of 3 previous lines of therapy were given, including thalidomide in 91%. Most patients were treated until progression or intolerable toxicity. The median number of cycles was 7 (range, 1-21+ cycles) with a maximum response after a median of 3 cycles (range, 1-10 cycles). The overall response rate was 69%, including complete response in 6%, very good partial response in 19%, and partial response in 44%. The response rate was not influenced by previous thalidomide and/or bortezomib treatment. The median time to progression (TTP) was 9 months and the median overall survival (OS) was 22 months. A significantly longer TTP was observed in patients who previously underwent allogeneic stem cell transplantation (12.5 months vs. 8 months; P = .036). Overall survival was significantly affected by performance status (P < .0001). Lenalidomide toxicity was predominantly hematologic (37%; Common Toxicity Criteria > or = 3) and the incidence of venous thrombotic events was low (5%) using the recommended prophylaxis. This analysis confirms that, outside clinical prospective trials, treatment with lenalidomide is highly effective and feasible in heavily pretreated patients with multiple myeloma.
  Clinical lymphoma, myeloma & leukemia 04/2010; 10(2):138-43.
• Article: Enhanced formation and survival of CD4+ CD25hi Foxp3+ T-cells in chronic lymphocytic leukemia.

  Margot Jak, Rogier Mous, Ester B M Remmerswaal, René Spijker, Annelieke Jaspers, Adriana Yagüe, Eric Eldering, René A W Van Lier, Marinus H J Van Oers
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  ABSTRACT: Recently, it has been described that patients with chronic lymphocytic leukemia (CLL) have increased numbers of regulatory T (T(reg)) cells. In the present study, we analysed the mechanism behind T(reg) cells expansion in CLL. Neither analysis of the T-cell receptor repertoire nor CD45 isoform expression of T(reg) cells from patients with CLL provided evidence for chronic (tumor) antigenic stimulation as a possible cause for T(reg) cells expansion in CLL. We found evidence however for increased formation of T(reg) cells via CD70 costimulation, because we observed that CD40 ligand activated CLL cells (which might be considered a model of lymph node CLL cells) strongly induced CD70-dependent formation of T(reg) cells. Reverse transcription-multiplex ligation-dependent probe amplification assay expression analysis of 34 apoptosis-regulating genes showed that in comparison with other CD4(+) T-cells, T(reg) cells from both healthy individuals (HD) and patients with CLL had a high expression of pro-apoptotic Noxa and a low expression of anti-apoptotic Bcl-2. Strikingly, Bcl-2 levels of T(reg) cells in patients with CLL were significantly higher than in HD. Finally, the different apoptotic profile resulted in differences at the functional level, because T(reg) cells from patients with CLL were more resistant to drug-induced apoptosis than T(reg) cells from HD. In conclusion, T(reg) cells in CLL may accumulate both by increased formation, facilitated by CD27-CD70 interaction in the lymph node proliferation centres, and decreased sensitivity to apoptosis because of a shifted Noxa-Bcl-2 balance.
  Leukemia & lymphoma 06/2009; 50(5):788-801. · 2.40 Impact Factor
• Source

  Available from: uu.nl

  Article: In vivo dynamics of stable chronic lymphocytic leukemia inversely correlate with somatic hypermutation levels and suggest no major leukemic turnover in bone marrow.

  Rogier van Gent, Arnon P Kater, Sigrid A Otto, A Jaspers, José A M Borghans, Nienke Vrisekoop, Mariëtte A T Ackermans, An F C Ruiter, Shulamiet Wittebol, Eric Eldering, Marinus H J van Oers, Kiki Tesselaar, Marie José Kersten, Frank Miedema
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  ABSTRACT: Although accumulating evidence indicates that chronic lymphocytic leukemia (CLL) is a disease with appreciable cell dynamics, it remains uncertain whether this also applies to patients with stable disease. In this study, (2)H(2)O was administered to a clinically homogeneous cohort of nine stable, untreated CLL patients. CLL dynamics in blood and bone marrow were determined and compared with normal B-cell dynamics in blood from five healthy individuals who underwent a similar (2)H(2)O labeling protocol. Average CLL turnover rates (0.08-0.35% of the clone per day) were approximately 2-fold lower than average B-cell turnover rates from healthy individuals (0.34-0.89%), whereas the rate at which labeled CLL cells in blood disappeared (0.00-0.39% of B cells per day) was approximately 10-fold lower compared with labeled B cells from healthy individuals (1.57-4.24% per day). Leukemic cell turnover variables inversely correlated with the level of somatic hypermutation of the CLL clone (IgVH mutations). Although CLL cells in bone marrow had a higher level of label enrichment than CLL cells in blood, no difference between proliferation rates and proapoptotic and antiapoptotic profiles of CLL cells from these compartments was observed. These data suggest that, in stable disease, there is a biological relationship between the degree of somatic hypermutation of the CLL clone and its dynamics in vivo. Furthermore, in contrast to lymph nodes, the bone marrow does not seem to be a major CLL proliferation site.
  Cancer Research 01/2009; 68(24):10137-44. · 7.86 Impact Factor
• Article: High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients.

  Mars B van 't Veer, Daphne de Jong, Marius MacKenzie, Hanneke C Kluin-Nelemans, Marinus H J van Oers, Jose Zijlstra, Anton Hagenbeek, Wim L J van Putten
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  ABSTRACT: Mantle cell lymphoma (MCL) has a dismal outcome when treated with conventional chemotherapy. This single arm phase 2 study evaluated intensive consolidation treatment of patients with newly diagnosed MCL up to the age of 65 years, responsive to R-CHOP (rituximab, cyclophosphamide, oncovin, adriamycin, prednisolone). Endpoints for evaluation were toxicity, failure-free survival (FFS) and overall survival (OS). Eighty-seven patients were treated with three cycles of R-CHOP. Sixty-six patients responded to R-CHOP with at least a partial response, 62 continued protocol treatment with high-dose cytarabine (Ara-C; 2000 mg/m(2), bid. over 4 d) and 61 patients received rituximab and stem cell harvest, followed by BEAM (carmustine, etoposide, Ara-C, melphalan) and autologous stem cell rescue. Non-haematological toxicity, grades III and IV, was seen in 8% of the patients after R-CHOP, in 22% after high-dose Ara-C and in 55% after BEAM. The overall response rate was 70% (complete response rate 64%, partial response rate 6%), FFS and OS at 4 years were 36 +/- 7% and 66 +/- 6%, respectively. The FFS and OS at 4 years from the evaluation after BEAM in the 61 R-CHOP responsive patients was 46 +/- 9% and 79 +/- 7%, respectively. In conclusion, high-dose Ara-C and BEAM with stem cell rescue in newly diagnosed MCL patients responsive to R-CHOP is a manageable treatment with respect to toxicity. This regimen leads to long-term, but probably not durable, remissions.
  British Journal of Haematology 12/2008; 144(4):524-30. · 4.94 Impact Factor
• Article: Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison.

  Jan J Cornelissen, Bronno van der Holt, Gregor E G Verhoef, Mars B van't Veer, Marinus H J van Oers, Harry C Schouten, Gert Ossenkoppele, Pieter Sonneveld, Johan Maertens, Marinus van Marwijk Kooy, Martijn R Schaafsma, Pierre W Wijermans, Douwe H Biesma, Shulamit Wittebol, Paul J Voogt, Joke W Baars, Pierre Zachée, Leo F Verdonck, Bob Löwenberg, Adriaan W Dekker
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  ABSTRACT: While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (+/- 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P = .01). After risk-group analysis, improved outcome was more pronounced in standard-risk patients with a donor, who experienced an overall survival of 69% at 5 years (P = .05). In conclusion, standard-risk ALL patients with a sibling donor may show favorable survival following SCT, due to both a strong reduction of relapse and a modest nonrelapse mortality. This trial is registered with http://www.trialregister.nl under trial ID NTR228.
  Blood 12/2008; 113(6):1375-82. · 9.90 Impact Factor
• Article: Array CGH analysis of chronic lymphocytic leukemia reveals frequent cryptic monoallelic and biallelic deletions of chromosome 22q11 that include the PRAME gene.

  Shelly R Gunn, Aswani R Bolla, Lynn L Barron, Mercedes E Gorre, Mansoor S Mohammed, David W Bahler, Clemens H M Mellink, Marinus H J van Oers, Michael J Keating, Alessandra Ferrajoli, Kevin R Coombes, Lynne V Abruzzo, Ryan S Robetorye
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  ABSTRACT: We used BAC array-based CGH to detect genomic imbalances in 187 CLL cases. Submicroscopic deletions of chromosome 22q11 were observed in 28 cases (15%), and the frequency of these deletions was second only to loss of the 13q14 region, the most common genomic aberration in CLL. Oligonucleotide-based array CGH analysis showed that the 22q11 deletions ranged in size from 0.34 Mb up to approximately 1 Mb. The minimally deleted region included the ZNF280A, ZNF280B, GGTLC2, and PRAME genes. Quantitative real-time PCR revealed that ZNF280A, ZNF280B, and PRAME mRNA expression was significantly lower in the 22q11 deletion cases compared to non-deleted cases.
  Leukemia research 12/2008; 33(9):1276-81. · 2.36 Impact Factor
• Article: Whole-genome scanning by array comparative genomic hybridization as a clinical tool for risk assessment in chronic lymphocytic leukemia.

  Shelly R Gunn, Mansoor S Mohammed, Mercedes E Gorre, Philip D Cotter, Jaeweon Kim, David W Bahler, Sergey N Preobrazhensky, Russell A Higgins, Aswani R Bolla, Sahar H Ismail, Daphne de Jong, Eric Eldering, Marinus H J van Oers, Clemens H M Mellink, Michael J Keating, Ellen J Schlette, Lynne V Abruzzo, Ryan S Robetorye
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  ABSTRACT: Array-based comparative genomic hybridization (array CGH) provides a powerful method for simultaneous genome-wide scanning and prognostic marker assessment in chronic lymphocytic leukemia (CLL). In the current study, commercially available bacterial artificial chromosome and oligonucleotide array CGH platforms were used to identify chromosomal alterations of prognostic significance in 174 CLL cases. Tumor genomes were initially analyzed by bacterial artificial chromosome array CGH followed by confirmation and breakpoint mapping using oligonucleotide arrays. Genomic changes involving loci currently interrogated by fluorescence in situ hybridization (FISH) panels were detected in 155 cases (89%) at expected frequencies: 13q14 loss (47%), trisomy 12 (13%), 11q loss (11%), 6q loss (7.5%), and 17p loss (4.6%). Genomic instability was the second most commonly identified alteration of prognostic significance with three or more alterations involving loci not interrogated by FISH panels identified in 37 CLL cases (21%). A subset of 48 CLL cases analyzed by six-probe FISH panels (288 total hybridizations) was concordant with array CGH results for 275 hybridizations (95.5%); 13 hybridizations (4.5%) were discordant because of clonal populations that comprised less than 30% of the sample. Array CGH is a powerful, cost-effective tool for genome-wide risk assessment in the clinical evaluation of CLL.
  Journal of Molecular Diagnostics 10/2008; 10(5):442-51. · 3.58 Impact Factor
• Article: miR-34a as part of the resistance network in chronic lymphocytic leukemia.

  Thorsten Zenz, Julia Mohr, Eric Eldering, Arnon P Kater, Andreas Bühler, Dirk Kienle, Dirk Winkler, Jan Dürig, Marinus H J van Oers, Daniel Mertens, Hartmut Döhner, Stephan Stilgenbauer
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  ABSTRACT: 17p (TP53) deletion identifies patients with chronic lymphocytic leukemia (CLL) who are resistant to chemotherapy. The members of the miR-34 family have been discovered to be direct p53 targets and mediate some of the p53-dependent effects. We studied miR-34a and miR-34b/c expression in a large cohort to define their potential role in refractory CLL. While no expression of miR-34b/c could be detected, we found variable expression levels of miR-34a. miR-34a levels were up-regulated after DNA damage in the presence of functional p53, but not in cases with 17p deletion (P < .001). We found a strong correlation of low miR-34a levels with impaired DNA damage response, TP53 mutations (without 17p deletion), and fludarabine-refractory disease (also in the absence of 17p deletion). Up-regulation of miR-34a after irradiation was associated with induction of Bax and p21, but not Puma. CLL cells with reduced miR-34a expression showed increased viability after DNA damage independently of 17p status. Therefore, low expression of miR-34a in CLL is associated with p53 inactivation but also chemotherapy-refractory disease, impaired DNA damage response, and apoptosis resistance irrespective of 17p deletion/TP53 mutation. The elucidation of mechanisms underlying miR-34a regulation and overcoming its role in chemotherapy resistance warrant further study.
  Blood 10/2008; 113(16):3801-8. · 9.90 Impact Factor
• Article: Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma.

  Franck Morschhauser, John Radford, Achiel Van Hoof, Umberto Vitolo, Pierre Soubeyran, Herve Tilly, Peter C Huijgens, Arne Kolstad, Francesco d'Amore, Marcos Gonzalez Diaz, Mario Petrini, Catherine Sebban, Pier Luigi Zinzani, Marinus H J van Oers, Wim van Putten, Angelika Bischof-Delaloye, Ama Rohatiner, Gilles Salles, Jens Kuhlmann, Anton Hagenbeek
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  ABSTRACT: We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 ((90)Y)-ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma in first remission. Patients with CD20(+) stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive (90)Y-ibritumomab tiuxetan (rituximab 250 mg/m(2) on day -7 and day 0 followed on day 0 by (90)Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment. A total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers. (90)Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio [HR] = 0.465; P < .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P < .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After (90)Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with (90)Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients. Consolidation of first remission with (90)Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.
  Journal of Clinical Oncology 10/2008; 26(32):5156-64. · 18.37 Impact Factor
• Article: No convincing evidence for a role of CD31-CD38 interactions in the pathogenesis of chronic lymphocytic leukemia.

  Sanne H Tonino, Rene Spijker, Dieuwertje M P Luijks, Marinus H J van Oers, Arnon P Kater
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  ABSTRACT: Although CD38, a marker of poor prognosis in chronic lymphocytic leukemia (CLL), is known primarily as an ecto-enzyme, it has also been ascribed a receptor function. Interaction with its proposed ligand CD31 expressed on nurse-like cells would result in proliferative and survival-signals. Yet, in CLL, both homotypic and heterotypic CD31-CD38 interactions are expected to be rather ubiquitous. We analyzed whether CD38-CD31 interactions result in proliferative and antiapoptotic signals. We found a high expression of CD31 on CLL, irrespective of CD38 expression. Coculture of CD38(high) CLL with endothelial cells or CD31 transfected fibroblasts, with or without blocking CD31 or CD38 antibodies, did not result in increased survival or proliferation. Analysis of gene expression of most known regulators of apoptosis revealed no influence of coculture with CD31-expressing feeder cells. In conclusion, our data do not support an important contribution of CD38 triggering by CD31 to the proliferative and antiapoptotic state of the leukemic clone.
  Blood 08/2008; 112(3):840-3. · 9.90 Impact Factor
• Source

  Available from: Erwan Piriou

  Article: Tight regulation of the Epstein-Barr virus setpoint: interindividual differences in Epstein-Barr virus DNA load are conserved after HIV infection.

  Erwan Piriou, Karel van Dort, Sigrid Otto, Marinus H J van Oers, Debbie van Baarle
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  ABSTRACT: Healthy individuals carry a constant number of Epstein-Barr virus-infected B cells in the peripheral blood over time. Here, we show that interindividual differences in Epstein-Barr virus DNA levels are maintained after HIV infection, providing evidence for the existence of an individual Epstein-Barr virus setpoint. Immune activation may contribute to the increase in this setpoint after human immunodeficiency virus seroconversion.
  Clinical Infectious Diseases 02/2008; 46(2):313-6. · 9.15 Impact Factor
• Article: Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

  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
• Article: Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial.

  Edo Vellenga, Wim L J van Putten, Mars B van 't Veer, Josée M Zijlstra, Willem E Fibbe, Marinus H J van Oers, Leo F Verdonck, Pierre W Wijermans, Gustaaf W van Imhoff, Pieternella J Lugtenburg, Peter C Huijgens
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  ABSTRACT: We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+ non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in complete remission (CR) and partial remission (PR) after 2 chemotherapy courses were eligible for autologous stem-cell transplantation. After the second chemotherapy cycle, 75% of the patients in the R-DHAP arm had responsive disease (CR or PR) versus 54% in the DHAP arm (P=.01). With a median follow-up of 24 months, there was a significant difference in failure-free survival (FFS24; 50% vs 24% vs, P<.001), and progression free survival (PFS24; 52% vs 31% P<.002) in favor of the R-DHAP arm. Cox-regression analysis demonstrated a significant effect of rituximab treatment on FFS24 (HR 0.41, 95% confidence interval [CI] 0.29-0.57 versus 0.51, 95% CI 0.37-0.70) and overall-survival (OS24: HR 0.60 [0.41-0.89] vs 0.76 [0.52-1.10]) when adjusted for time since upfront treatment, age, World Health Organization performance status, and secondary age-adjusted international prognostic index. These results demonstrate improved FFS and PFS for relapsed aggressive B-cell NHL if rituximab is added to the re-induction chemotherapy regimen.
  Blood 01/2008; 111(2):537-43. · 9.90 Impact Factor
• Article: Cellular immune therapy for chronic lymphocytic leukemia.

  Arnon P Kater, Marinus H J van Oers, Thomas J Kipps
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  ABSTRACT: Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for chemotherapy-resistant leukemia-cell subclones. Cellular immune therapy promises to mitigate these complications and potentially provide for curative treatment. Most experience with this is in the use of allogeneic hematopoietic stem-cell transplantation (allo-HSCT), in which graft-versus-leukemia (GVL) effects can be observed and shown responsible for long-term disease-free survival. However, use of allo-HSCT for CLL is limited because of the lack of suitable donors and the treatment-related morbidity/mortality for elderly patients, who constitute the majority at risk for developing this disease. The GVL effect, however, suggests there are specific CLL-associated antigens that could be targeted in autologous cellular immune therapy. Effective strategies for this will have to overcome the disease-related acquired immune deficiency and the capacity of the leukemia-cell to induce T-cell tolerance, thereby compromising the activity of even conventional vaccines in patients with this disease. We will discuss the different strategies being developed to overcome these limitations that might provide for effective cellular immune therapy of CLL.
  Blood 11/2007; 110(8):2811-8. · 9.90 Impact Factor