Bone Marrow Transplants from Unrelated Donors for Patients with Chronic Myeloid Leukemia
John A. Hansen, M.D., Theodore A. Gooley, Ph.D., Paul J. Martin, M.D., Frederick Appelbaum, M.D., Thomas R. Chauncey, M.D., Reginald A. Clift, F.I.M.L.S., Effie W. Petersdorf, M.D., Jerald Radich, M.D., Jean E. Sanders, M.D., Rainer F. Storb, M.D., Keith M. Sullivan, M.D., and Claudio Anasetti, M.D.
Background Chronic myeloid leukemia can be cured by marrow transplantationfrom an HLA-identical sibling donor. The use of transplantsfrom unrelated donors is an option for the 70 percent of patientswithout an HLA-identical sibling, but the morbidity and mortalityassociated with such transplants have been cause for concern.We analyzed the safety and efficacy of transplants from unrelateddonors for the treatment of chronic myeloid leukemia and identifiedvariables that predict a favorable outcome.
Methods Between May 1985 and December 1994, 196 patients withPhiladelphia chromosome–positive chronic myeloid leukemiain chronic phase received marrow transplants from unrelateddonors.
Results The median follow-up was 5 years (range, 1.2 to 10.1).Graft failure occurred in 5 percent of patients who could beevaluated. Acute graft-versus-host disease of grade III or IVseverity was observed in 35 percent of patients who receivedHLA-matched transplants, and the estimated cumulative incidenceof relapse at five years was 10 percent. The Kaplan–Meierestimate of survival at five years was 57 percent. Survivalwas adversely affected by an interval from diagnosis to transplantationof one year or more, an HLA-DRB1 mismatch, a high body-weightindex, and an age of more than 50 years. Survival was improvedby the prophylactic use of fluconazole and ganciclovir. TheKaplan–Meier estimate of survival at five years was 74percent (95 percent confidence interval, 62 to 86 percent) forpatients who were 50 years of age or younger who received atransplant from an HLA-matched donor within one year after diagnosis.
Conclusions Transplantation of marrow from an HLA-matched, unrelateddonor is safe and effective therapy for selected patients withchronic myeloid leukemia.
Source Information
From the Fred Hutchinson Cancer Research Center (J.A.H., T.A.G., P.J.M., F.A., T.R.C., R.A.C., E.W.P., J.R., J.E.S., R.F.S., K.M.S., C.A.), the Veterans Affairs Medical Center (T.R.C.), and the University of Washington School of Medicine (J.A.H., P.J.M., F.A., T.R.C., E.W.P., J.R., J.E.S., R.F.S., K.M.S., C.A.) — all in Seattle.
Address reprint requests to Dr. Hansen at the Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024.
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[Abstract][Full Text]
Bunjes, D., Buchmann, I., Duncker, C., Seitz, U., Kotzerke, J., Wiesneth, M., Dohr, D., Stefanic, M., Buck, A., Harsdorf, S. V., Glatting, G., Grimminger, W., Karakas, T., Munzert, G., Dohner, H., Bergmann, L., Reske, S. N.
(2001). Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study. Blood
98: 565-572
[Abstract][Full Text]
Ulrich, C. M., Yasui, Y., Storb, R., Schubert, M. M., Wagner, J. L., Bigler, J., Ariail, K. S., Keener, C. L., Li, S., Liu, H., Farin, F. M., Potter, J. D.
(2001). Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood
98: 231-234
[Abstract][Full Text]
Laughlin, M. J., Barker, J., Bambach, B., Koc, O. N., Rizzieri, D. A., Wagner, J. E., Gerson, S. L., Lazarus, H. M., Cairo, M., Stevens, C. E., Rubinstein, P., Kurtzberg, J.
(2001). Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical-Cord Blood from Unrelated Donors. NEJM
344: 1815-1822
[Abstract][Full Text]
Soiffer, R. J., Weller, E., Alyea, E. P., Mauch, P., Webb, I. L., Fisher, D. C., Freedman, A. S., Schlossman, R. L., Gribben, J., Lee, S., Anderson, K. C., Marcus, K., Stone, R. M., Antin, J. H., Ritz, J.
(2001). CD6+ Donor Marrow T-Cell Depletion as the Sole Form of Graft-Versus-Host Disease Prophylaxis in Patients Undergoing Allogeneic Bone Marrow Transplant From Unrelated Donors. JCO
19: 1152-1159
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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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Marr, K. A., Seidel, K., Slavin, M. A., Bowden, R. A., Schoch, H. G., Flowers, M. E. D., Corey, L., Boeckh, M.
(2000). Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood
96: 2055-2061
[Abstract][Full Text]
Nash, R. A., Antin, J. H., Karanes, C., Fay, J. W., Avalos, B. R., Yeager, A. M., Przepiorka, D., Davies, S., Petersen, F. B., Bartels, P., Buell, D., Fitzsimmons, W., Anasetti, C., Storb, R., Ratanatharathorn, V.
(2000). Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood
96: 2062-2068
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Mielcarek, M., Leisenring, W., Torok-Storb, B., Storb, R.
(2000). Graft-versus-host disease and donor-directed hemagglutinin titers after ABO-mismatched related and unrelated marrow allografts: evidence for a graft-versus-plasma cell effect. Blood
96: 1150-1156
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Craddock, C., Szydlo, R. M., Klein, J. P., Dazzi, F., Olavarria, E., van Rhee, F., Pocock, C., Cwynarski, K., Apperley, J. F., Goldman, J. M.
(2000). Estimating leukemia-free survival after allografting for chronic myeloid leukemia: a new method that takes into account patients who relapse and are restored to complete remission. Blood
96: 86-90
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Yu, X.-Z., Bidwell, S. J., Martin, P. J., Anasetti, C.
(2000). CD28-Specific Antibody Prevents Graft-Versus-Host Disease in Mice. J. Immunol.
164: 4564-4568
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Reddy, V., Moreb, J., Mehta;, P., Dazzi, F., Szydlo, R. M., Goldman, J. M.
(2000). Donor lymphocyte infusions for CML: possible effects of age and mobilization. Blood
95: 2994-2995
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McGlave, P. B., Shu, X. O., Wen, W., Anasetti, C., Nademanee, A., Champlin, R., Antin, J. H., Kernan, N. A., King, R., Weisdorf, D. J.
(2000). Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the National Marrow Donor Program. Blood
95: 2219-2225
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Deeg, H. J., Shulman, H. M., Anderson, J. E., Bryant, E. M., Gooley, T. A., Slattery, J. T., Anasetti, C., Fefer, A., Storb, R., Appelbaum, F. R.
(2000). Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood
95: 1188-1194
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Kantarjian, H., Melo, J. V., Tura, S., Giralt, S., Talpaz, M.
(2000). Chronic Myelogenous Leukemia: Disease Biology and Current and Future Therapeutic Strategies. ASH Education Book
2000: 90-109
[Abstract][Full Text]
Hehlmann, R., Hochhaus, A., Kolb, H.-J., Hasford, J., Gratwohl, A., Heimpel, H., Siegert, W., Finke, J., Ehninger, G., Holler, E., Berger, U., Pfirrmann, M., Muth, A., Zander, A., Fauser, A. A., Heyll, A., Nerl, C., Hossfeld, D. K., Loffler, H., Pralle, H., Tobler, W. Q.{b.}e. a. A.
(1999). Interferon-alpha Before Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia Does Not Affect Outcome Adversely, Provided It Is Discontinued at Least 90 Days Before the Procedure. Blood
94: 3668-3677
[Abstract][Full Text]
Tseng, L.-H., Lin, M.-T., Hansen, J. A., Gooley, T., Pei, J., Smith, A. G., Martin, E. G., Petersdorf, E. W., Martin, P. J.
(1999). Correlation Between Disparity for the Minor Histocompatibility Antigen HA-1 and the Development of Acute Graft-Versus-Host Disease After Allogeneic Marrow Transplantation. Blood
94: 2911-2914
[Abstract][Full Text]
Martin, P. J., Rowley, S. D., Anasetti, C., Chauncey, T. R., Gooley, T., Petersdorf, E. W., van Burik, J.-A., Flowers, M. E.D., Storb, R., Appelbaum, F. R., Hansen, J. A.
(1999). A Phase I-II Clinical Trial to Evaluate Removal of CD4 Cells and Partial Depletion of CD8 Cells From Donor Marrow for HLA-Mismatched Unrelated Recipients. Blood
94: 2192-2199
[Abstract][Full Text]
Green, A., Clarke, E., Hunt, L., Canterbury, A., Lankester, A., Hale, G., Waldmann, H., Goodman, S., Cornish, J. M., Marks, D. I., Steward, C. G., Oakhill, A., Pamphilon, D. H.
(1999). Children With Acute Lymphoblastic Leukemia Who Receive T-Cell-Depleted HLA Mismatched Marrow Allografts From Unrelated Donors Have an Increased Incidence of Primary Graft Failure but a Similar Overall Transplant Outcome. Blood
94: 2236-2246
[Abstract][Full Text]
Silver, R. T., Woolf, S. H., Hehlmann, R., Appelbaum, F. R., Anderson, J., Bennett, C., Goldman, J. M., Guilhot, F., Kantarjian, H. M., Lichtin, A. E., Talpaz, M., Tura, S.
(1999). An Evidence-Based Analysis of the Effect of Busulfan, Hydroxyurea, Interferon, and Allogeneic Bone Marrow Transplantation in Treating the Chronic Phase of Chronic Myeloid Leukemia: Developed for the American Society of Hematology. Blood
94: 1517-1536
[Abstract][Full Text]
Faderl, S., Talpaz, M., Estrov, Z., Kantarjian, H. M.
(1999). Chronic Myelogenous Leukemia: Biology and Therapy. ANN INTERN MED
131: 207-219
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(1999). Monitoring Treatment and Survival in Chronic Myeloid Leukemia. JCO
17: 1858-1858
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Sawyers, C. L.
(1999). Chronic Myeloid Leukemia. NEJM
340: 1330-1340
[Full Text]
Small, T.N., Papadopoulos, E.B., Boulad, F., Black, P., Castro-Malaspina, H., Childs, B.H., Collins, N., Gillio, A., George, D., Jakubowski, A., Heller, G., Fazzari, M., Kernan, N., MacKinnon, S., Szabolcs, P., Young, J.W., O'Reilly, R.J.
(1999). Comparison of Immune Reconstitution After Unrelated and Related T-Cell-Depleted Bone Marrow Transplantation: Effect of Patient Age and Donor Leukocyte Infusions. Blood
93: 467-480
[Abstract][Full Text]
Lee, S. J., Anasetti, C., Kuntz, K. M., Patten, J., Antin, J. H., Weeks, J. C.
(1998). The Costs and Cost-Effectiveness of Unrelated Donor Bone Marrow Transplantation for Chronic Phase Chronic Myelogenous Leukemia. Blood
92: 4047-4052
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Petersdorf, E. W., Gooley, T. A., Anasetti, C., Martin, P. J., Smith, A. G., Mickelson, E. M., Woolfrey, A. E., Hansen, J. A.
(1998). Optimizing Outcome After Unrelated Marrow Transplantation by Comprehensive Matching of HLA Class I and II Alleles in the Donor and Recipient. Blood
92: 3515-3520
[Abstract][Full Text]
Morton, A. J., Gooley, T., Hansen, J. A., Appelbaum, F. R., Bruemmer, B., Bjerke, J. W., Clift, R., Martin, P. J., Petersdorf, E. W., Sanders, J. E., Storb, R., Sullivan, K. M., Woolfrey, A., Anasetti, C.
(1998). Association Between Pretransplant Interferon-alpha and Outcome After Unrelated Donor Marrow Transplantation for Chronic Myelogenous Leukemia in Chronic Phase. Blood
92: 394-401
[Abstract][Full Text]
(1998). Marrow Transplants from Unrelated Donors in CML. JWatch General
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Hehlmann, R.
(1998). A Chance of Cure for Every Patient with Chronic Myeloid Leukemia?. NEJM
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