title: Donor lymphocyte infusion for relapsed hematological malignancies after allogeneic hematopoietic cell transplantation: prognostic relevance of the initial CD3+ T cell dose.
abstract: The impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patients with chronic myeloid leukemia but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3(+) cell dose on graft-versus-host disease (GVHD) and overall survival after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high- or reduced-intensity conditioning. The cohort included 225 patients. Initial DLI CD3(+) cell dose per kilogram of recipient body weight was ≤ 1 × 10(7) (n = 84; group A), >1.0 to <10 × 10(7) (n = 58; group B), and ≥ 10 × 10(7) (n = 66; group C). The initial cell dose was unknown for the remaining 17 patients. Cumulative incidence rates of GVHD at 12 months after DLI were 21%, 45%, and 55% for groups A, B, and C, respectively. Multivariate analysis showed that initial DLI CD3(+) cell ≥ 10 × 10(7) dose per kilogram is associated with an increased risk of GVHD after DLI (P = .03). Moreover, an initial DLI CD3(+) cell dose of 10 × 10(7) or higher did not decrease the risk of relapse and did not improve overall survival. Thus, these results support the use of less than 10 × 10(7) CD3(+) cell per kilogram as the initial cell dose of DLI for treatment of persistent or recurrent hematological malignancy after HCT.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. mbar@u.washington.edu
authors.forename: Merav
authors.initials: M
authors.lastname: Bar
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D017252:CD3 Complex; D019653:Myeloablative Agonists