Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

• Type of Material: Article
• Authors: Olle Ringden, Karolinska University Hospital; Smriti Shrestha, Medical College of Wisconsin; Gisela Tunes da Silva, University of Sao Paulo; Mei-Jie Zhang, Medical College of Wisconsin; Angela Dispenzieri, Mayo Clinic; Mats Remberger, Karolinska University Hospital; Rammurti Kamble, Baylor College of Medicine; Cesar O. Freytes, South Texas Veterans Health Care Systems; Robert Peter Gale, Celgene Corporation; John Gibson, Royal Prince Alfred Hospital; Vikas Gupta, Princess Margaret Hospital; Leona Holmberg, Fred Hutchinson Cancer Research Center; Hillard Lazarus, University Hospitals Case Medical Center; Philip McCarthy, Roswell Park Cancer Institute; Kenneth Meehan, Dartmount-Hitchcock Medical Center; Harry Schouten, University Hospital Maastricht; Gustavo A. Milone, Angelica Ocampo-Fundaleu; Sagar Lonial, Emory University; Parameswaran N Hari, Medical College of Wisconsin
• Language: English
• Date: 2012-06-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Macmillan Publishers Limited All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/bmt.2011.192
• Title of Journal or Parent Work: Bone Marrow Transplantation
• ISSN: 0268-3369
• Volume: 47
• Issue: 6
• Start Page: 831
• End Page: 837
• Grant/Funding Information: Complete funding list available in full text.; The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI); and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.;; Olle Ringdén is supported by grants from the Swedish Cancer Society; the Children’s Cancer Foundation; the Swedish Research Council; the Cancer Society in Stockholm; and Karolinska Institutet.
• Keywords: VERSUS-HOST DISEASE; Immunology; RECIPIENTS; CYCLOSPORINE; Transplantation; Biophysics; reduced intensity; TRIAL; myeloma; Oncology; BONE-MARROW-TRANSPLANTATION; graft-vs-host disease; Life Sciences & Biomedicine; STEM-CELL TRANSPLANTATION; CHRONIC GRAFT; DIAGNOSED MULTIPLE-MYELOMA; Hematology; allogeneic; Science & Technology; EUROPEAN GROUP; CHRONIC LEUKEMIA
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (≥grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.