Reduced Intensity Conditioning and Allogeneic Stem-Cell Transplantation: Determining Its Role in Multiple Myeloma
Authors: Karl S. Peggs, Stephen Mackinnon, Kwee Yong, Ashraf Badros
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.151 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12377972 Reduced Intensity Conditioning and Allogeneic Stem-Cell Transplantation: Determining Its Role in Multiple Myeloma Karl S. PeggsxKarl S. PeggsSearch for articles by this author , Stephen MackinnonxStephen MackinnonSearch for articles by this author , Kwee YongxKwee YongSearch for articles by this author Ashraf BadrosxAshraf BadrosSearch for articles by this author Show More University College London Hospitals, London, United KingdomUniversity of Maryland, Baltimore, MD https://doi.org/10.1200/JCO.2002.99.151 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15102002In Reply:In our study,1 high-risk multiple myeloma (MM) patients “as defined by chromosome 13 abnormalities in association with B-2 microglobulin level of 2.5 mg/L or higher” who received a planned tandem allogeneic transplantation early in the disease course after an autologous stem-cell transplantation (auto-SCT) has improved disease-free and overall survivals. The duration of follow-up is limited; however, the fact that none of these patients had relapsed at a median follow-up of 21 months (range, 17 to 37 months) is encouraging. The effect in these patients is clearly related to graft-versus-myeloma effect rather than a second cycle of high-dose melphalan, because median disease-free survival for high-risk MM patients after tandem auto-SCT is less than 9 months.2Graft-versus-host disease (GVHD) continues to be a problem with nonmyeloablative allogeneic transplantations. In our study, all responses, especially in refractory patients, followed the development of GVHD. Actually, the development of chronic GVHD was an independent prognostic factor for better disease-free survival after allogeneic transplantation.3 The importance of GVHD is re-emphasized by the high relapse rate seen in responding patients after adequate control of GVHD. Although it is presumed that T cells are the primary mediators of immune responses after allogeneic transplantations; the number of CD3+ cells, in our study, did not correlate with the severity of GVHD or durability of graft-versus-myeloma responses in the small subset of patients who received donor lymphocyte infusion (unpublished data). In addition, the role of other effector cells (eg, NK and LAK) or the contributions of CD34+ cells that were infused with the granulocyte colony-stimulating factor mobilized CD3+ cells have not been fully evaluated. Whether pre-emptive donor lymphocyte infusion in the setting of persistent minimal residual disease can prevent relapse after allogeneic transplantation remains under investigation.Until mature data are available on nonmyeloablative allogeneic transplantations, we believe that good-risk MM patients should receive a planned tandem auto-SCT upfront, even in presence of a matched sibling donor. These patients have an excellent quality of life and a complete remission rate of 40% to 50%, with a median survival of 9.5 years. Many of these patients are in continuous remissions more than 7 years after tandem auto-SCT.4New therapies that target the bone marrow microenvironment, overcome drug resistance, or modify the immune responses should be integrated in future studies to further improve the outcome of allogeneic transplantations in MM.1. Badros A, Barlogie B, Siegel E, et al: Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning. J Clin Oncol 20:: 1295,2002-1303, Link, Google Scholar2. Desikan R, Barlogie B, Sawyer J, et al: Results of high-dose therapy for 1000 patients with multiple myeloma: Durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 95:: 4008,2000-4010, Crossref, Medline, Google Scholar3. Lee CK, Badros A, Barlogie B, et al: Prognostic factors in non-myeloablative allogeneic transplantation for patients with high-risk multiple myeloma. J Clin Oncol 21:: 416a,,2002 (abstr 1660) Google Scholar4. Tricot G, Trey S, Sawyer J, et al: Predicting long term (≥ 5 yr.) event-free survival in multiple myeloma patients following planned tandem autotransplants. Br J Haematol 116:: 1,2002-8, Crossref, Medline, Google Scholar