title: Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia.
abstract: Eighty patients with chronic myeloid leukemia (CML) underwent T cell-depleted stem cell transplantation from an HLA-identical sibling, with add-back of donor T cells on days 30 to 45 and days 60 to 100 in patients in whom grade 2 or greater acute graft-versus-host disease (GVHD) developed. The outcomes for 54 patients with chronic-phase (CP) and 26 with advanced-phase (AP) disease were as follows: overall survival, 85% +/- 5% versus 36% +/- 10%; transplantation-related mortality (TRM), 13% +/- 5% versus 43% +/- 11%; and current leukemia-free survival, 76% +/- 6% versus 34% +/- 9%. The day-30 lymphocyte count (LC30) was strongly associated with outcome. For patients in CP with counts greater than the median of 0.30 x 10(9)/L, survival was 100% versus 70% +/- 9% (P = .003); current LFS 100% versus 56% +/- 9% (P = .002); and TRM 0% versus 26% +/- 8% (P = .006). Higher-than-median LC30 correlated significantly with molecular remission (MR) at 3, 6, and 12 months and with higher CD34 doses. Lymphocyte subset analysis performed in 20 patients available for phenotyping showed that LC30 was highly correlated with absolute CD56+CD3- natural killer cell numbers (NK30), which also predicted for survival and MR. CD34 cell dose, LC30, and NK30, but not day-30 CD3+ cell count, were highly correlated and were significant predictors of transplantation outcome. These results suggest that transplanted CD34 cell doses greater than 5 x 10(6)/kg may improve outcomes by increasing the early recovery of NK cells.
authors.affiliation: Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg 10, Hatfield CRC, Bethesda, MD 20892-1202, USA.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
authors.forename: Aldemar
authors.initials: A
authors.lastname: Montero
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlander
authors.forename: Charles S
authors.initials: CS
authors.lastname: Carter
authors.forename: Susan
authors.initials: S
authors.lastname: Leitman
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Read
authors.forename: Richard
authors.initials: R
authors.lastname: Childs
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology*; D016896:Treatment Outcome