ORIGINAL ARTICLE Genetically identical twin transplantation for chronic lymphocytic leukemia SZ Pavletic 1 , G Zhou 2 , K Sobocinski 3 , G Marti 4 , K Doney 5 , J DiPersio 6 , W Feremans 7 , L Foroni 8 , S Goodman 9 , G Prentice 8 , C LeMaistre 10 , G Bandini 11 , A Ferrant 12 , N Jacobsen 13 , I Khouri 14 , RP Gale 3 , A Wiestner 15 , S Giralt 14 , E Montserrat 16 , WC Chan 2 and C Bredeson 17 , for the Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, USA 1 National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA; 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; 3 Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA; 4 Division of Cell and Gene Therapies, United States Food and Drug Administration, CBER, Bethesda, MD, USA; 5 Department of Medicine, University of Washington, Seattle, WA, USA; 6 Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 7 Clinic of Hematology, Erasme University Hospital (ULB), Brussels, Belgium; 8 Department of Haematology, Royal Free Hospital and School of Medicine, University College, London, UK; 9 Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; 10 Division of Adult Stem Cell Transplantation, Texas Transplant Institute, San Antonio, TX, USA; 11 Department of Hematology-Oncology, Institute of Hematology, Sant’ Orsola University Hospital, Bologna, Italy; 12 Department of Hematology, Cliniques Universitaires Saint-Luc, Universite catholique de Louvain, Brussels, Belgium; 13 Department of Hematology, Rigshospitalet University Hospital, Copenhagen, Denmark; 14 Department of Stem Cell Transplantation, MD Anderson Cancer Center, University of Texas, Houston, TX, USA; 15 National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA; 16 Department of Hematology, Institute of Hematology and Oncology, Hospital Clinic, IDIBAPS, University of Barcelona, Spain and 17 Division of Neoplastic Diseases, Medical College of Wisconsin, Milwaukee, WI, USA We identified 19 persons with B-cell chronic lymphocytic leukemia (CLL) who received genetically identical twin blood cell or bone marrow transplants after high-dose conditioning. Ten are alive (eight disease-free) with a median follow-up of 89 months (range, 31–171 months); 5-year relapse rate was 50% (95% confidence interval (CI), 26–73%). Estimated 5-year survival and disease-free survival were 61% (95% CI, 37–82%) and 45% (95% CI, 23–68%). In two of four patients tested at 12 and 21 months by polymerase chain reaction no evidence of residual CLL was detected post-transplant. In one recipient who relapsed at 6 years, molecular studies showed a different CLL clone from that detected pretransplant. This clone was subse- quently identified in the donor suggesting transfer of occult leukemia at the time of transplant. Genetically identical twin transplants can result in long-term disease-free survival and molecular remissions, these data suggest the potential for CLL control in the absence of allogeneic graft-versus-leukemia effect. The case of leukemia transfer indicates the need for careful evaluation of donors prior to graft collection. Leukemia (2007) 21, 2452–2455; doi:10.1038/sj.leu.2404928; published online 30 August 2007 Keywords: hematopoietic stem cell transplantation; identical twin; CLL Introduction Studies of genetically identical twin blood cell and bone marrow transplants can provide unique insights into disease mechanisms and therapies. Graft rejection cannot occur and graft-versus-host disease (GVHD)-related or other allogeneic antileukemia effects are absent. In this setting there is no prior graft exposure to cytotoxic therapy and there should be no cancer cells contaminating the graft that could be transferred to the recipient. Because genetically-identical twin transplants are rare, studies by large international registries are needed; several are reported. 1–5 Rates of leukemia relapse in twins are substantially higher than in allograft recipients including those with and without GvHD. 6 These data suggest allogeneic immune-mediated graft-versus-leukemia (GVL) effect operates after most allotransplants for leukemia. In contrast, leukemia- relapse risk is generally higher after autotransplants than after twin transplants 1,2,7 suggesting leukemia contamination of the graft. 3,8 There is good evidence of a GVL effect after allotransplants for B-cell chronic lymphocytic leukemia (CLL) where an important proportion of patients achieve durable clinical and molecular remissions. 9–13 In contrast, autotransplants have high rates of relapse. 14–16 Here, we report 19 patients with CLL who received genetically identical twin transplants. Our objectives were to determine clinical outcomes. Materials and methods Nineteen patients with CLL were transplanted between 1980 and 2001 and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR), (n ¼ 15), the Fred Hutchinson Cancer Research Center (n ¼ 3) or the European Group for Blood and Marrow Transplantation (n ¼ 1). Data were prospectively collected using the standard CIBMTR core forms, additional Supplementary Information was requested from transplant centers at the time of study using predesigned CLL- specific data collection forms available at: http://www.cibm- tr.org/DATA/report_forms_idx.html. Genetically identical twin state was confirmed independently at each site by history, RBC- antigen and HLA-typing and/or by DNA-polymorphism ana- lyses. No subject received GVHD prophylaxis. Complementar- ity-determining region (CDR)III of IgH-gene PCR amplification Received 25 May 2007; revised 14 July 2007; accepted 24 July 2007; published online 30 August 2007 Correspondence: Dr SZ Pavletic, Experimental Transplantation and Immunology Branch, Graft-versus-Host and Autoimmunity Unit, National Cancer Institute, 9000 Rockville Pike, 10 Center Drive, Bethesda, MD 20892-1203, USA. E-mail: pavletis@mail.nih.gov Leukemia (2007) 21, 2452–2455 & 2007 Nature Publishing Group All rights reserved 0887-6924/07 $30.00 www.nature.com/leu