Critical Factors in Optimizing Graft-Versus-Leukemia Effect for Relapsed Leukemias
Authors: Suparno Chakrabarti, John E. Levine, Robert H. Collins
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.2002.20.11.2756 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12039941 Critical Factors in Optimizing Graft-Versus-Leukemia Effect for Relapsed Leukemias Suparno ChakrabartixSuparno ChakrabartiSearch for articles by this author John E. LevinexJohn E. LevineSearch for articles by this author , Robert H. Collins JrxRobert H. Collins JrSearch for articles by this author Show More Bristol Royal Hospital for Sick Children, Bristol, United KingdomUniversity of Michigan, Ann Arbor, MIUniversity of Texas Southwestern Medical Center, Dallas, TX https://doi.org/10.1200/JCO.2002.20.11.2756 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 OncologyResponse01062002In Reply:Dr Chakrabarti notes that acute leukemia relapse rates in adults were lower when less immunosuppression was given in the first 10 days after myeloablative transplantation. Recipients of lower-dose immunosuppression who were younger than 30 years had superior survival, but this benefit did not hold true for patients older than 30 years.1 On the basis of this observation, Chakrabarti speculates that the optimal time to achieve the graft-versus-leukemia (GVL) effect is to administer donor lymphocyte infusion (DLI) earlier than the 10 to 14 days following chemotherapy, as was performed in our study.2 However, earlier administration of DLI may increase the risk of graft-versus-host disease (GVHD) unless postinfusion immunosuppression is provided. In a myeloablative murine model, Xun et al3 showed that delaying T-cell infusion from day 0 to day 4 after total-body irradiation (TBI) led to a substantial reduction in GVHD -related mortality. Conditioning-related tissue damage and subsequent inflammatory cytokine release might be important mechanisms for the risk of lethal GVHD after T-cell infusion.4 Although Chakrabarti puts forth an interesting hypothesis, further study will be needed to determine whether an earlier DLI will result in a greater GVL effect, worse GVHD, both, or neither.Chakrabarti interprets the failure to observe a survival benefit of GVHD after DLI in our study to mean that a GVL effect was not operative. This is not necessarily true. Horowitz et al5 showed that the GVL effect need not occur in the context of clinically evident GVHD. However, in the absence of a randomized comparison, we make no claim of superiority of our approach over any other. For example, Pawson et al6 recently reported overall survival of 60% and disease-free survival of 28% at 58 months after a second nonmyeloablative transplant for acute leukemia relapse following a failed first allogeneic transplant. We believe that further investigation into inducing meaningful GVL effects while minimizing regimen-related and GVHD-related mortality is warranted for patients with advanced myeloid leukemia relapse after allogeneic stem-cell transplantation.1. Bacigalupo A, Lamparelli T, Gualandi F, et al: Increased risk of leukemia relapse with high dose cyclosporine after allogeneic marrow transplantation for acute leukemia: 10 year follow-up of a randomized study. Blood 98:: 3174,2001-3175, Crossref, Medline, Google Scholar2. Levine JE, Braun T, Penza SL, et al: Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol 20:: 405,2002-412, Link, Google Scholar3. Xun CQ, Tsuchida M, Thompson JS: Delaying transplantation after total body irradiation is a simple and effective way to reduce acute graft-versus-host disease mortality after major H2 incompatible transplantation. Transplantation 64:: 297,1997-302, Crossref, Medline, Google Scholar4. Hill GR, Crawford JM, Cooke KR, et al: Total body irradiation and acute graft-versus-host disease: The role of gastrointestinal damage and inflammatory cytokines. Blood 90:: 3204,1997-3213, Crossref, Medline, Google Scholar5. Horowitz MM, Gale RP, Sondel PM, et al: Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:: 555,1990-562, Crossref, Medline, Google Scholar6. Pawson R, Potter MN, Theocharous P, et al: Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant. Br J Haematol 115:: 622,2001-629, Crossref, Medline, Google Scholar