title: Impact of immune modulation with in vivo T-cell depletion and myleoablative total body irradiation conditioning on outcomes after unrelated donor transplantation for childhood acute lymphoblastic leukemia.
abstract: To determine whether in vivo T-cell depletion, which lowers GVHD, abrogates the antileukemic benefits of myeloablative total body irradiation-based conditioning and unrelated donor transplantation, in the present study, we analyzed 715 children with acute lymphoblastic leukemia. Patients were grouped for analysis according to whether conditioning included antithymocyte globulin (ATG; n = 191) or alemtuzumab (n = 132) and no in vivo T-cell depletion (n = 392). The median follow-up time was 3.5 years for the ATG group and 5 years for the alemtuzumab and T cell-replete groups. Using Cox regression analysis, we compared transplantation outcomes between groups. Compared with no T-cell depletion, grade 2-4 acute and chronic GVHD rates were significantly lower after in vivo T-cell depletion with ATG (relative risk [RR] = 0.66; P = .005 and RR = 0.55; P < .0001, respectively) or alemtuzumab (RR = 0.09; P < .003 and RR = 0.21; P < .0001, respectively). Despite lower GVHD rates after in vivo T-cell depletion, nonrelapse mortality, relapse, overall survival, and leukemia-free survival (LFS) did not differ significantly among the treatment groups. The 3-year probabilities of LFS after ATG-containing, alemtuzumab-containing, and T cell-replete transplantations were 43%, 49%, and 46%, respectively. These data suggest that in vivo T-cell depletion lowers GVHD without compromising LFS among children with acute lymphoblastic leukemia who are undergoing unrelated donor transplantation with myeloablative total body irradiation-based regimens.
authors.affiliation: Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom. paul.veys@gosh.nhs.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wynn
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
authors.forename: Wensheng
authors.initials: W
authors.lastname: He
authors.forename: Denise
authors.initials: D
authors.lastname: Bonney
authors.forename: John
authors.initials: J
authors.lastname: Craddock
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cornish
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.forename: Reggie E
authors.initials: RE
authors.lastname: Duerst
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Neena
authors.initials: N
authors.lastname: Kapoor
authors.forename: Carrie
authors.initials: C
authors.lastname: Kitko
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
authors.forename: Victor A
authors.initials: VA
authors.lastname: Lewis
authors.forename: Colin
authors.initials: C
authors.lastname: Steward
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Paul A
authors.initials: PA
authors.lastname: Carpenter
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D042381:Granulocyte Precursor Cells / Q000473:pathology / Q000528:radiation effects; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D007223:Infant; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000276:immunology / Q000628:therapy*; D012042:Registries / Q000706:statistics & numerical data; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014916:Whole-Body Irradiation / Q000379:methods