title: Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy.
abstract: Donor lymphocyte infusions (DLI) are an effective treatment for patients with chronic myeloid leukemia (CML) in relapse after allografting but the optimal cell dose has yet to be identified. To address this question, we investigated the factors affecting the dose required to achieve remission (effective cell dose, (ECD)) in 81 patients treated with an escalating dose regimen. The overall proportion of patients who achieved a molecular remission was 88%. The cumulative proportion of remitters increased significantly at each dose level. With a CD3(+) cell dose < or =10(7)/kg, 56% of patients in molecular/cytogenetic relapse obtained molecular remission, whereas only 20% of those in hematologic relapse did so. At the same cell dose, 58% of patients who received lymphocytes from volunteer unrelated donors achieved remission, as compared to 29% of those who received DLI from sibling donors. We conclude that the response to DLI is dose-dependent and that the ECD is influenced by the quantity and phase of CML at relapse and degree of donor/recipient histocompatibility.
authors.affiliation: Department of Hematology, Imperial College at Hammersmith Hospital, London, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Simula
authors.forename: S
authors.initials: S
authors.lastname: Marktel
authors.forename: C
authors.initials: C
authors.lastname: Fozza
authors.forename: J
authors.initials: J
authors.lastname: Kaeda
authors.forename: R M
authors.initials: RM
authors.lastname: Szydlo
authors.forename: E
authors.initials: E
authors.lastname: Nadal
authors.forename: M
authors.initials: M
authors.lastname: Bua
authors.forename: A
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: E
authors.initials: E
authors.lastname: Kanfer
authors.forename: D
authors.initials: D
authors.lastname: Marin
authors.forename: E
authors.initials: E
authors.lastname: Olavarria
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.forename: F
authors.initials: F
authors.lastname: Dazzi
mesh_terms: D000208:Acute Disease; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D017710:Lymphocyte Transfusion; D012008:Recurrence