Transplantation of Bone Marrow as Compared with Peripheral-Blood Cells from HLA-Identical Relatives in Patients with Hematologic Cancers
William I. Bensinger, M.D., Paul J. Martin, M.D., Barry Storer, Ph.D., Reginald Clift, F.I.M.L.S., Steven J. Forman, M.D., Robert Negrin, M.D., Ashwin Kashyap, M.D., Mary E.D. Flowers, M.D., Kathy Lilleby, R.N., Thomas R. Chauncey, M.D., Rainer Storb, M.D., and Frederick R. Appelbaum, M.D.
Background In recipients of allogeneic hematopoietic-cell transplants,peripheral-blood cells mobilized with the use of filgrastim(recombinant granulocyte colony-stimulating factor) engraftmore rapidly than bone marrow. However, the relative effectsof these techniques on the rates of acute and chronic graft-versus-hostdisease, overall survival, and disease-free survival have notbeen determined in randomized studies.
Methods Between March 1996 and July 1999, 172 patients (12 to55 years of age) with hematologic cancer were randomly assignedto receive either bone marrow or filgrastim-mobilized peripheral-bloodcells from HLA-identical relatives for hematopoietic rescueafter the treatment of hematologic cancer with high doses ofchemotherapy, with or without radiation.
Results The recovery of both neutrophils and platelets was fasterwith peripheral-blood cells than with marrow (P<0.001 forboth comparisons). The cumulative incidence of grade II, III,or IV acute graft-versus-host disease at 100 days was 64 percentwith peripheral-blood cells and 57 percent with marrow (hazardratio, 1.21; 95 percent confidence interval, 0.81 to 1.81; P=0.35).The cumulative incidence of chronic graft-versus-host diseasewas 46 percent with peripheral-blood cells and 35 percent withmarrow (hazard ratio, 1.16; 95 percent confidence interval,0.71 to 1.90; P= 0.54). The estimated overall probability ofsurvival at two years was 66 percent with peripheral-blood cellsand 54 percent with marrow (hazard ratio for death, 0.62; 95percent confidence interval, 0.38 to 1.02; P= 0.06). The rateof disease-free survival at two years was 65 percent with peripheral-bloodcells and 45 percent with marrow (hazard ratio for relapse ordeath, 0.60; 95 percent confidence interval, 0.38 to 0.95; P=0.03).
Conclusions In patients given high-dose chemotherapy, with orwithout radiation, for the treatment of hematologic cancer,allogeneic peripheral-blood cells used for hematopoietic rescuerestore blood counts faster than allogeneic bone marrow, withoutincreasing the risk of graft-versus-host disease.
Source Information
From the Clinical Division, Fred Hutchinson Cancer Research Center, Seattle (W.I.B., P.J.M., B.S., R.C., M.E.D.F., K.L., T.R.C., R.S., F.R.A.); the Division of Oncology, University of Washington, Seattle (W.I.B., P.J.M., B.S., M.E.D.F., T.R.C., R.S., F.R.A.); the Divisions of Hematology and Bone Marrow Transplantation, City of Hope Medical Center, Duarte, Calif. (S.J.F., A.K.); and the Division of Bone Marrow Transplantation, Stanford University, Stanford, Calif. (R.N.). Other authors were Scott Rowley, M.D., and Shelly Heimfeld, Ph.D., Fred Hutchinson Cancer Research Center and University of Washington, Seattle; and Karl Blume, M.D., Stanford University, Stanford, Calif.
Address reprint requests to Dr. Bensinger at the Division of Oncology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, or at wbensing{at}fhcrc.org.
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(2002). Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood
100: 415-419
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Guardiola, P., Runde, V., Bacigalupo, A., Ruutu, T., Locatelli, F., Boogaerts, M. A., Pagliuca, A., Cornelissen, J. J., Schouten, H. C., Carreras, E., Finke, J., van Biezen, A., Brand, R., Niederwieser, D., Gluckman, E., de Witte, T. M.
(2002). Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood
99: 4370-4378
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Mullighan, C. G., Heatley, S., Doherty, K., Szabo, F., Grigg, A., Hughes, T. P., Schwarer, A. P., Szer, J., Tait, B. D., Bik To, L., Bardy, P. G.
(2002). Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation. Blood
99: 3524-3529
[Abstract][Full Text]
Bittencourt, H., Rocha, V., Chevret, S., Socie, G., Esperou, H., Devergie, A., Dal Cortivo, L., Marolleau, J.-P., Garnier, F., Ribaud, P., Gluckman, E.
(2002). Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation. Blood
99: 2726-2733
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Woolfrey, A. E., Anasetti, C., Storer, B., Doney, K., Milner, L. A., Sievers, E. L., Carpenter, P., Martin, P., Petersdorf, E., Appelbaum, F. R., Hansen, J. A., Sanders, J. E.
(2002). Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood
99: 2002-2008
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Korbling, M., Katz, R. L., Khanna, A., Ruifrok, A. C., Rondon, G., Albitar, M., Champlin, R. E., Estrov, Z.
(2002). Hepatocytes and Epithelial Cells of Donor Origin in Recipients of Peripheral-Blood Stem Cells. NEJM
346: 738-746
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Veys, P., Owens, C.
(2002). Respiratory infections following haemopoietic stem cell transplantation in children. Br Med Bull
61: 151-174
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Elmaagacli, A. H., Basoglu, S., Peceny, R., Trenschel, R., Ottinger, H., Lollert, A., Runde, V., Grosse-Wilde, H., Beelen, D. W., Schaefer, U. W.
(2002). Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia. Blood
99: 1130-1135
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Auffermann-Gretzinger, S., Lossos, I. S., Vayntrub, T. A., Leong, W., Grumet, F. C., Blume, K. G., Stockerl-Goldstein, K. E., Levy, R., Shizuru, J. A.
(2002). Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients. Blood
99: 1442-1448
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Tzachanis, D., Berezovskaya, A., Nadler, L. M., Boussiotis, V. A.
(2002). Blockade of B7/CD28 in mixed lymphocyte reaction cultures results in the generation of alternatively activated macrophages, which suppress T-cell responses. Blood
99: 1465-1473
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Kang, E. M., Areman, E. M., David-Ocampo, V., Fitzhugh, C., Link, M. E., Read, E. J., Leitman, S. F., Rodgers, G. P., Tisdale, J. F.
(2002). Mobilization, collection, and processing of peripheral blood stem cells in individuals with sickle cell trait. Blood
99: 850-855
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Mehta, J., Singhal, S., Cutler, C., Antin, J. H.
(2002). Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell Transplantation: A Little Methotrexate Goes a Long Way. JCO
20: 603-606
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Giles, F. J., Keating, A., Goldstone, A. H., Avivi, I., Willman, C. L., Kantarjian, H. M.
(2002). Acute Myeloid Leukemia. ASH Education Book
2002: 73-110
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Druker, B. J., O'Brien, S. G., Cortes, J., Radich, J.
(2002). Chronic Myelogenous Leukemia. ASH Education Book
2002: 111-135
[Abstract][Full Text]
Hoelzer, D., Gokbuget, N., Ottmann, O., Pui, C.-H., Relling, M. V., Appelbaum, F. R., van Dongen, J. J.M., Szczepanski, T.
(2002). Acute Lymphoblastic Leukemia. ASH Education Book
2002: 162-192
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Maloney, D. G., Sandmaier, B. M., Mackinnon, S., Shizuru, J. A.
(2002). Non-Myeloablative Transplantation. ASH Education Book
2002: 392-421
[Abstract][Full Text]
Weissinger, F., Sandmaier, B. M., Maloney, D. G., Bensinger, W. I., Gooley, T., Storb, R.
(2001). Decreased transfusion requirements for patients receiving nonmyeloablative compared with conventional peripheral blood stem cell transplants from HLA-identical siblings. Blood
98: 3584-3588
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Morton, J., Hutchins, C., Durrant, S.
(2001). Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells. Blood
98: 3186-3191
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Zaucha, J. M., Gooley, T., Bensinger, W. I., Heimfeld, S., Chauncey, T. R., Zaucha, R., Martin, P. J., Flowers, M. E. D., Storek, J., Georges, G., Storb, R., Torok-Storb, B.
(2001). CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation. Blood
98: 3221-3227
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Korbling, M., Anderlini, P.
(2001). Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter?. Blood
98: 2900-2908
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Cutler, C., Giri, S., Jeyapalan, S., Paniagua, D., Viswanathan, A., Antin, J. H.
(2001). Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis. JCO
19: 3685-3691
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Schwarzenberger, P., Huang, W., Oliver, P., Byrne, P., La Russa, V., Zhang, Z., Kolls, J. K.
(2001). IL-17 Mobilizes Peripheral Blood Stem Cells with Short- and Long-Term Repopulating Ability in Mice. J. Immunol.
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Storek, J., Wells, D., Dawson, M. A., Storer, B., Maloney, D. G.
(2001). Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation. Blood
98: 489-491
[Abstract][Full Text]
Storek, J., Dawson, M. A., Storer, B., Stevens-Ayers, T., Maloney, D. G., Marr, K. A., Witherspoon, R. P., Bensinger, W., Flowers, M. E. D., Martin, P., Storb, R., Appelbaum, F. R., Boeckh, M.
(2001). Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood
97: 3380-3389
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Singhal, S., Powles, R., Mehta, J., Klumpp, T. R., Goker, H., Bensinger, W. I., Storer, B., Appelbaum, F. R.
(2001). Hematopoietic Reconstitution by Transplantation of Stem Cells from Bone Marrow or Blood. NEJM
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Rowley, S. D., Donaldson, G., Lilleby, K., Bensinger, W. I., Appelbaum, F. R.
(2001). Experiences of donors enrolled in a randomized study of allogeneic bone marrow or peripheral blood stem cell transplantation. Blood
97: 2541-2548
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Druker, B. J., Sawyers, C. L., Capdeville, R., Ford, J. M., Baccarani, M., Goldman, J. M.
(2001). Chronic Myelogenous Leukemia. ASH Education Book
2001: 87-112
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