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

• 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
• Journal Title: Bone Marrow Transplantation
• Volume: Volume 47, Number 6
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals | 2012-06-01, Pages 831-837
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/bmt.2011.192
• Subjects: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biophysics; Oncology; Hematology; Immunology; Transplantation; graft-vs-host disease; reduced intensity; allogeneic; myeloma; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA; VERSUS-HOST DISEASE; CHRONIC GRAFT; CHRONIC LEUKEMIA; EUROPEAN GROUP; RECIPIENTS; TRIAL; CYCLOSPORINE

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.