This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baron, F. Articles by Storb, R. Search for Related Content PubMed PubMed Citation Articles by Baron, F. Articles by Storb, R.

Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning

From the Clinical Research Division, Fred Hutchinson Cancer Research Center; University of Washington School of Medicine; Children's Hospital and Regional Medical Center; Veterans Affairs Puget Sound Health Care System, Seattle, WA; and Department of Hematology, University of Liège, Liège, Belgium

Address reprint requests to Rainer Storb, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024; e-mail: rstorb{at}fhcrc.org

PURPOSE: We have used a nonmyeloablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m²/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy.

PATIENTS AND METHODS: We analyzed GVT effects in 322 patients given grafts from HLA-matched related (n = 192) or unrelated donors (n = 130).

RESULTS: Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD; P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003).

CONCLUSION: New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning.

Supported by grant Nos. CA78902, HL36444, CA18029, CA92058, DK064715, and CA15704 from the National Institutes of Health, Department of Health and Human Services, Bethesda, MD. R.S. received support from the Laura Landro Salomon Endowment Fund. F.B. is a research associate of the National Fund for Scientific Research, Belgium, and is supported in part by postdoctoral grants from the Fulbright Commission.

F.B. and M.B.M. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				D. Valcarcel, R. Martino, D. Caballero, J. Martin, C. Ferra, J. B. Nieto, A. Sampol, M. T. Bernal, J. L. Pinana, L. Vazquez, et al. Sustained Remissions of High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome After Reduced-Intensity Conditioning Allogeneic Hematopoietic Transplantation: Chronic Graft-Versus-Host Disease Is the Strongest Factor Improving Survival J. Clin. Oncol., February 1, 2008; 26(4): 577 - 584. [Abstract] [Full Text] [PDF]

				E. Castermans, F. Baron, E. Willems, N. Schaaf-Lafontaine, N. Meuris, A. Gothot, J.-F. Vanbellighen, C. Herens, L. Seidel, V. Geenen, et al. Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning Haematologica, February 1, 2008; 93(2): 240 - 247. [Abstract] [Full Text] [PDF]

				A. A. Jakubowski, T. N. Small, J. W. Young, N. A. Kernan, H. Castro-Malaspina, K. C. Hsu, M.-A. Perales, N. Collins, C. Cisek, M. Chiu, et al. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin Blood, December 15, 2007; 110(13): 4552 - 4559. [Abstract] [Full Text] [PDF]

				F. Ciceri, C. Bonini, S. Marktel, E. Zappone, P. Servida, M. Bernardi, A. Pescarollo, A. Bondanza, J. Peccatori, S. Rossini, et al. Antitumor effects of HSV-TK engineered donor lymphocytes after allogeneic stem-cell transplantation Blood, June 1, 2007; 109(11): 4698 - 4707. [Abstract] [Full Text] [PDF]

				N. Durakovic, V. Radojcic, M. Skarica, K. B. Bezak, J. D. Powell, E. J. Fuchs, and L. Luznik Factors governing the activation of adoptively transferred donor T cells infused after allogeneic bone marrow transplantation in the mouse Blood, May 15, 2007; 109(10): 4564 - 4574. [Abstract] [Full Text] [PDF]

				J. H. Antin Reduced-Intensity Stem Cell Transplantation: "...whereof a little More than a little is by much too much." King Henry IV, part 1, I, 2 Hematology, January 1, 2007; 2007(1): 47 - 54. [Abstract] [Full Text] [PDF]

				F. Baron, R. Storb, B. E. Storer, M. B. Maris, D. Niederwieser, J. A. Shizuru, T. R. Chauncey, B. Bruno, S. J. Forman, P. A. McSweeney, et al. Factors Associated With Outcomes in Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning After Failed Myeloablative Hematopoietic Cell Transplantation J. Clin. Oncol., September 1, 2006; 24(25): 4150 - 4157. [Abstract] [Full Text] [PDF]

				L. Pirson, F. Baron, N. Meuris, O. Giet, E. Castermans, R. Greimers, I. Di Stefano, A. Gothot, and Y. Beguin Despite Inhibition of Hematopoietic Progenitor Cell Growth In Vitro, the Tyrosine Kinase Inhibitor Imatinib Does Not Impair Engraftment of Human CD133+ Cells into NOD/SCID{beta}2mNull Mice Stem Cells, July 1, 2006; 24(7): 1814 - 1821. [Abstract] [Full Text] [PDF]

				N. S. Majhail, D. J. Weisdorf, J. E. Wagner, T. E. Defor, C. G. Brunstein, and L. J. Burns Comparable results of umbilical cord blood and HLA-matched sibling donor hematopoietic stem cell transplantation after reduced-intensity preparative regimen for advanced Hodgkin lymphoma Blood, May 1, 2006; 107(9): 3804 - 3807. [Abstract] [Full Text] [PDF]

				B. L. Scott and B. M. Sandmaier Outcomes with Myeloid Malignancies Hematology, January 1, 2006; 2006(1): 381 - 389. [Abstract] [Full Text] [PDF]

				I. F. Khouri Reduced-Intensity Regimens in Allogeneic Stem-Cell Transplantation for Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia Hematology, January 1, 2006; 2006(1): 390 - 397. [Abstract] [Full Text] [PDF]

				M. L. Sorror, M. B. Maris, R. Storb, F. Baron, B. M. Sandmaier, D. G. Maloney, and B. Storer Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT Blood, October 15, 2005; 106(8): 2912 - 2919. [Abstract] [Full Text] [PDF]