Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer

Summary

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects of donor stem cell transplant and to see how well it works in treating patients with high-risk hematologic cancer.

Timeline

Start

2005-05

Primary completion

2011-03

Completion

2012-03

Publications

• Background McGlave PB, Shu XO, Wen W, Anasetti C, Nademanee A, Champlin R, Antin JH, Kernan NA, King R, Weisdorf DJ. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood. 2000 Apr 1;95(7):2219-25.
• Background Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A, Matthews D, Sanders JE, Storb R, Appelbaum FR, Anasetti C. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant. 2000 Aug;26(4):397-404. doi: 10.1038/sj.bmt.1702519.
• Background Weisdorf DJ, Billett AL, Hannan P, Ritz J, Sallan SE, Steinbuch M, Ramsay NK. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia. Blood. 1997 Oct 15;90(8):2962-8.
• Background Anderson JE, Anasetti C, Appelbaum FR, Schoch G, Gooley TA, Hansen JA, Buckner CD, Sanders JE, Sullivan KM, Storb R. Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia. Br J Haematol. 1996 Apr;93(1):59-67. doi: 10.1046/j.1365-2141.1996.4811022.x.
• Background Izutsu K, Kanda Y, Ohno H, Sao H, Ogawa H, Miyazaki Y, Kawa K, Kodera Y, Kato S, Morishima Y, Hirai H; Japan Marrow Donor Program. Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program. Blood. 2004 Mar 1;103(5):1955-60. doi: 10.1182/blood-2003-03-0937. Epub 2003 Nov 6.
• Background Shaw BE, Peggs K, Bird JM, Cavenagh J, Hunter A, Alejandro Madrigal J, Russell NH, Sirohi B, Towlson K, Williams CD, Marks DI; Clinical Trials Committee of the British Society of Blood and Marrow Transplantation. The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma. Br J Haematol. 2003 Dec;123(5):886-95. doi: 10.1046/j.1365-2141.2003.04714.x.
• Background Davies SM, Kollman C, Anasetti C, Antin JH, Gajewski J, Casper JT, Nademanee A, Noreen H, King R, Confer D, Kernan NA. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood. 2000 Dec 15;96(13):4096-102.
• Background Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8. doi: 10.1056/NEJM199804023381405.
• Background Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C, Maloney DG, Storb R. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004 Aug 15;104(4):961-8. doi: 10.1182/blood-2004-02-0545. Epub 2004 Apr 27.
• Background Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L, Buckner CD, Anasetti C, Appelbaum FR, Badger C, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989 May 1;73(6):1720-8.
• Background Mehta J, Singhal S. Graft-versus-myeloma. Bone Marrow Transplant. 1998 Nov;22(9):835-43. doi: 10.1038/sj.bmt.1701459.
• Background Jones RJ, Ambinder RF, Piantadosi S, Santos GW. Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood. 1991 Feb 1;77(3):649-53.
• Background Porter DL, Connors JM, Van Deerlin VM, Duffy KM, McGarigle C, Saidman SL, Leonard DG, Antin JH. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol. 1999 Apr;17(4):1234. doi: 10.1200/JCO.1999.17.4.1234.
• Background O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood. 1993 Sep 15;82(6):1695-700.
• Background Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6.
• Background Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG, Sandmaier BM, Storb R. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood. 2004 Sep 1;104(5):1550-8. doi: 10.1182/blood-2004-03-0804. Epub 2004 May 18.
• Background Escalon MP, Champlin RE, Saliba RM, Acholonu SA, Hosing C, Fayad L, Giralt S, Ueno NT, Maadani F, Pro B, Donato M, McLaughlin P, Khouri IF. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol. 2004 Jun 15;22(12):2419-23. doi: 10.1200/JCO.2004.09.092.
• Background Khouri IF, Lee MS, Saliba RM, Andersson B, Anderlini P, Couriel D, Hosing C, Giralt S, Korbling M, McMannis J, Keating MJ, Champlin RE. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol. 2004 Jan;32(1):28-35. doi: 10.1016/j.exphem.2003.09.021.
• Background Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, Gajewski J, Hansen JA, Henslee-Downey J, McCullough J, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med. 1993 Mar 4;328(9):593-602. doi: 10.1056/NEJM199303043280901.
• Background Champlin RE, Passweg JR, Zhang MJ, Rowlings PA, Pelz CJ, Atkinson KA, Barrett AJ, Cahn JY, Drobyski WR, Gale RP, Goldman JM, Gratwohl A, Gordon-Smith EC, Henslee-Downey PJ, Herzig RH, Klein JP, Marmont AM, O'Reilly RJ, Ringden O, Slavin S, Sobocinski KA, Speck B, Weiner RS, Horowitz MM. T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities. Blood. 2000 Jun 15;95(12):3996-4003.
• Background Perez-Simon JA, Kottaridis PD, Martino R, Craddock C, Caballero D, Chopra R, Garcia-Conde J, Milligan DW, Schey S, Urbano-Ispizua A, Parker A, Leon A, Yong K, Sureda A, Hunter A, Sierra J, Goldstone AH, Linch DC, San Miguel JF, Mackinnon S; Spanish and United Kingdom Collaborative Groups for Nonmyeloablative Transplantation. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood. 2002 Nov 1;100(9):3121-7. doi: 10.1182/blood-2002-03-0701.
• Background Byrne JL, Stainer C, Cull G, Haynes AP, Bessell EM, Hale G, Waldmann H, Russell NH. The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. Bone Marrow Transplant. 2000 Feb;25(4):411-7. doi: 10.1038/sj.bmt.1702165.
• Background Faulkner RD, Craddock C, Byrne JL, Mahendra P, Haynes AP, Prentice HG, Potter M, Pagliuca A, Ho A, Devereux S, McQuaker G, Mufti G, Yin JL, Russell NH. BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood. 2004 Jan 15;103(2):428-34. doi: 10.1182/blood-2003-05-1406. Epub 2003 Sep 11.

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Indications