International Myeloma Working Group Consensus Statement Regarding the Current Status of Allogeneic Stem-Cell Transplantation for Multiple Myeloma
ABSTRACT To define consensus statement regarding allogeneic stem-cell transplantation (Allo-SCT) as a treatment option for multiple myeloma (MM) on behalf of International Myeloma Working Group.
In this review, results from prospective and retrospective studies of Allo-SCT in MM are summarized.
Although the introduction of reduced-intensity conditioning (RIC) has lowered the high treatment-related mortality associated with myeloablative conditioning, convincing evidence is lacking that Allo-RIC improves the survival compared with autologous stem-cell transplantation.
New strategies are necessary to make Allo-SCT safer and more effective for patients with MM. Until this is achieved, Allo-RIC in myeloma should only be recommended in the context of clinical trials.
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ABSTRACT: In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single centre analysis we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). We included a total of 138 patients who underwent 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma). Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs 26.5%, P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable, independently predicted for superior progression-free and overall survival (median progression-free survival: 37.5 vs 6.3 months, P<0.001; median overall survival: 115.3 vs 31.0 months, P=0.004). Clinicians should be aware of the benign nature of this phenomenon, and secondary monoclonal gammopathy of undetermined significance should not be confused with relapse or progression of disease. Trial is registered with trialregister.nl; HOVON 108: NTR 2958.Haematologica 09/2014; 99(12). DOI:10.3324/haematol.2014.111104 · 5.87 Impact Factor
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ABSTRACT: Background Consensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine’s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents. Findings Thirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal’s consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases. Conclusion Guidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor’s product to enhance transparency.PLoS ONE 10/2014; 9(10). DOI:10.1371/journal.pone.0110469 · 3.53 Impact Factor
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ABSTRACT: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD). Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses. We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses potentially associated with the curative capacity of this immunotherapeutic approach.PLoS ONE 11/2014; 9(11):e113764. DOI:10.1371/journal.pone.0113764 · 3.53 Impact Factor