title: A phase I/II study of chemotherapy followed by donor lymphocyte infusion plus interleukin-2 for relapsed acute leukemia after allogeneic hematopoietic cell transplantation.
abstract: The efficacy of donor lymphocyte infusion (DLI) for treatment of relapsed acute leukemia after allogeneic hematopoietic cell transplantation is limited. We hypothesized that interleukin-2 (IL-2) combined with DLI after chemotherapy might augment graft-versus-leukemia effects. To identify a safe and effective IL-2 regimen, a phase I/II study of DLI plus IL-2 therapy was performed for such patients. After chemotherapy, 17 patients received DLI (1 × 10(8) CD3/kg for patients with related donors, and 0.1 × 10(8) CD3/kg for those with unrelated donors) and an escalating dose of induction IL-2 (1.0, 2.0, or 3.0 × 10(6) IU/m(2)/day representing levels I [n = 7], Ia [n = 9], and II [n = 1]) for 5 days followed by maintenance (1.0 × 10(6) IU/m(2)/day) for 10 days as a continuous intravenous infusion. Unacceptable IL-2-related toxicities developed in 1 patient at level I, 2 at level Ia, and 1 at level II. Grades III-IV acute graft-versus-host disease (aGVHD) developed in 5 patients, and extensive chronic GVHD (cGVHD) developed in 8. Eight patients had a complete remission after chemotherapy prior to DLI, and 2 additional patients had a complete remission after DLI plus IL-2 therapy. In conclusion, the maximal tolerated induction dose of IL-2 combined with DLI appears to be 1.0 × 10(6) IU/m(2)/day. IL-2 administration after DLI might increase the incidence of cGVHD.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.forename: Alexander
authors.initials: A
authors.lastname: Fefer
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Petersdorf
authors.forename: Jean E
authors.initials: JE
authors.lastname: Sanders
authors.forename: Rainer F
authors.initials: RF
authors.lastname: Storb
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
mesh_terms: D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D007938:Leukemia / Q000150:complications / Q000628:therapy*; D017710:Lymphocyte Transfusion / Q000379:methods*; D020714:Maximum Tolerated Dose; D016879:Salvage Therapy / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2