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Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease S Mackinnon, EB Papadopoulos, MH Carabasi, L Reich, NH Collins, F Boulad, H Castro-Malaspina, BH Childs, AP Gillio and NA Kernan Departments of Medicine and Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD. Volume 86, Issue 4, pp. 1261-1268, 08/15/1995 Copyright © 1995 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Leen, A. Christin, G. D. Myers, H. Liu, C. R. Cruz, P. J. Hanley, A. A. Kennedy-Nasser, K. S. Leung, A. P. Gee, R. A. Krance, et al. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation Blood, November 5, 2009; 114(19): 4283 - 4292. [Abstract] [Full Text] [PDF] M. Haniffa, F. Ginhoux, X.-N. Wang, V. Bigley, M. Abel, I. Dimmick, S. Bullock, M. Grisotto, T. Booth, P. Taub, et al. Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation J. Exp. Med., February 16, 2009; 206(2): 371 - 385. [Abstract] [Full Text] [PDF] A. Hayat, S. R. McCann, S. 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