PURPOSE: A fludarabine-based "nonmyeloablative" preparative regimen was investigated in 42 patients with hematological malignancies receiving hematopoietic stem cell grafts from unrelated volunteer donors. EXPERIMENTAL DESIGN: Recipient conditioning consisted of fludarabine 30 mg/m(2) on days -6 to -2 and i.v. busulfan 3.3 mg/kg on days -6 to -5. Antithymocyte globuline was added at 2.5 mg/kg i.v. on days -5 to -2. The patients were grafted with bone marrow (n = 13) or peripheral blood stem cells either unmanipulated (n = 20) or CD34+ selected (n = 9). Graft-versus-host disease prophylaxis was performed with cyclosporine A (CsA, n = 12), CsA/methotrexate (n = 12), or CsA/mycophenolate mofetil (n = 18). RESULTS: With a median follow-up of 13 months (range, 5-26 months), the actuarial disease-free survival is 64% and 38% for patients with lymphoid malignancies and standard-risk leukemia compared with only 14% for patients with high-risk disease. The main cause of treatment failure was relapse of disease in high-risk patients (n = 14). An increased incidence of primary (n = 1) or secondary graft-failure (n = 8) was observed (21%). Chimerism analysis of CD56+/CD3--sorted natural killer (NK) cells, available in 10 patients, showed an impaired increase of donor NK cell chimerism between day 10 and 30 after transplantation in three of four patients with graft failure, whereas the percentage of donor NK cells surpassed 75% in all of the six patients with stable engraftment. CONCLUSIONS: Unrelated transplants after dose-reduced conditioning are associated with a higher risk of graft-failure. Pretransplant host immunosuppression has to be optimized to overcome resistance to grafts from unrelated donors after nonmyeloablative conditioning therapy.
PURPOSE: A fludarabine-based "nonmyeloablative" preparative regimen was investigated in 42 patients with hematological malignancies receiving hematopoietic stem cell grafts from unrelated volunteer donors. EXPERIMENTAL DESIGN: Recipient conditioning consisted of fludarabine 30 mg/m(2) on days -6 to -2 and i.v. busulfan 3.3 mg/kg on days -6 to -5. Antithymocyte globuline was added at 2.5 mg/kg i.v. on days -5 to -2. The patients were grafted with bone marrow (n = 13) or peripheral blood stem cells either unmanipulated (n = 20) or CD34+ selected (n = 9). Graft-versus-host disease prophylaxis was performed with cyclosporine A (CsA, n = 12), CsA/methotrexate (n = 12), or CsA/mycophenolate mofetil (n = 18). RESULTS: With a median follow-up of 13 months (range, 5-26 months), the actuarial disease-free survival is 64% and 38% for patients with lymphoid malignancies and standard-risk leukemia compared with only 14% for patients with high-risk disease. The main cause of treatment failure was relapse of disease in high-risk patients (n = 14). An increased incidence of primary (n = 1) or secondary graft-failure (n = 8) was observed (21%). Chimerism analysis of CD56+/CD3--sorted natural killer (NK) cells, available in 10 patients, showed an impaired increase of donor NK cell chimerism between day 10 and 30 after transplantation in three of four patients with graft failure, whereas the percentage of donor NK cells surpassed 75% in all of the six patients with stable engraftment. CONCLUSIONS: Unrelated transplants after dose-reduced conditioning are associated with a higher risk of graft-failure. Pretransplant host immunosuppression has to be optimized to overcome resistance to grafts from unrelated donors after nonmyeloablative conditioning therapy.
Authors: S Fuji; S W Kim; S Yano; S Hagiwara; H Nakamae; M Hidaka; T Ito; K Ohashi; K Hatanaka; A Takami; S Kurosawa; T Yamashita; T Yamaguchi; T Fukuda Journal: Bone Marrow Transplant Date: 2015-11-09 Impact factor: 5.483
Authors: Roger S Riley; Michael Idowu; Alden Chesney; Shawn Zhao; John McCarty; Lawrence S Lamb; Jonathan M Ben-Ezra Journal: J Clin Lab Anal Date: 2005 Impact factor: 2.352
Authors: Ran Reshef; Elizabeth O Hexner; Alison W Loren; Noelle V Frey; Edward A Stadtmauer; Selina M Luger; James K Mangan; Saar I Gill; Pavel Vassilev; Kathryn A Lafferty; Jacqueline Smith; Vivianna M Van Deerlin; Rosemarie Mick; David L Porter Journal: Biol Blood Marrow Transplant Date: 2014-07-10 Impact factor: 5.742