PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell-depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell-depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.
PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell-depleted bone marrow transplants in acute leukemiapatients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemiapatients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemiapatients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell-depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.
Authors: Barbara Spitzer; Ann A Jakubowski; Esperanza B Papadopoulos; Kirsten Fuller; Patrick D Hilden; James W Young; Juliet N Barker; Guenther Koehne; Miguel-Angel Perales; Katharine C Hsu; Marcel R van den Brink; Nancy A Kernan; Susan E Prockop; Andromachi Scaradavou; Hugo Castro-Malaspina; Richard J O'Reilly; Farid Boulad Journal: Biol Blood Marrow Transplant Date: 2017-07-12 Impact factor: 5.742
Authors: C Bonini; J Peccatori; M T L Stanghellini; L Vago; A Bondanza; N Cieri; R Greco; M Bernardi; C Corti; G Oliveira; E Zappone; C Traversari; C Bordignon; F Ciceri Journal: Bone Marrow Transplant Date: 2015-06 Impact factor: 5.483
Authors: H Joachim Deeg; Margaret O'Donnell; Jakub Tolar; Rajni Agarwal; Richard E Harris; Stephen A Feig; Mary C Territo; Robert H Collins; Peter A McSweeney; Edward A Copelan; Shakila P Khan; Ann Woolfrey; Barry Storer Journal: Blood Date: 2006-05-09 Impact factor: 22.113
Authors: Marcel van den Brink; Markus Uhrberg; Lorenz Jahn; John F DiPersio; Michael A Pulsipher Journal: Bone Marrow Transplant Date: 2018-01-24 Impact factor: 5.483
Authors: Ann A Jakubowski; Trudy N Small; Nancy A Kernan; Hugo Castro-Malaspina; Nancy Collins; Guenther Koehne; Katharine C Hsu; Miguel A Perales; Genovefa Papanicolaou; Marcel R M van den Brink; Richard J O'Reilly; James W Young; Esperanza B Papadopoulos Journal: Biol Blood Marrow Transplant Date: 2011-01-11 Impact factor: 5.742