title: Transplantation in remission improves the disease-free survival of patients with advanced myelodysplastic syndromes treated with myeloablative T cell-depleted stem cell transplants from HLA-identical siblings.
abstract: From 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (> or =5% blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in hematologic remission; 4 were in a second refractory cytopenia phase (26 responders); 8 had failed to achieve remission; and 2 of the responders had progression or relapse of their MDS (10 failures). No post-transplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2 had primary graft failure; and 2 died before engraftment. Only 3 patients developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3 yrs post-transplantation, the overall survival (OS) was 54% in the responders; 31% in the untreated group; and 0% in the failure group (P=.0004). The disease free survival (DFS) was 50%, 15% and 0% in each group respectively (P=.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs post-transplantation for the responders was 23%; for the untreated group was 38%; and for the failures was 50%. The CI of non-relapse mortality at 2-yrs post-transplantation, for the responders was 23%; for the untreated group was 38%; and for the failures was 40%. All survivors achieved a Karnofsky Performance Status (KPS) of > or =90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long-term remissions following a myeloablative T cell depleted allogeneic HSCT.
authors.affiliation: The Allogeneic Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. castro-h@mskcc.org
authors.forename: Hugo
authors.initials: H
authors.lastname: Castro-Malaspina
authors.forename: Ann A
authors.initials: AA
authors.lastname: Jabubowski
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Perales
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: Katharine
authors.initials: K
authors.lastname: Hsu
authors.forename: Michelle
authors.initials: M
authors.lastname: Chiu
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Collins
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Jhanwar
authors.forename: Marcel
authors.initials: M
authors.lastname: van den Brink
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008212:Lymphocyte Depletion; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000628:therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D035781:Siblings; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods; D014185:Transplantation, Isogeneic / Q000379:methods*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D006680:HLA Antigens