title: A pilot study evaluating interleukin-2-activated hematopoietic stem cell transplantation for hematologic malignancies.
abstract: Cytotoxic effector cells are generated when autologous hematopoietic cells (HSC) are cultured with IL-2 for 24 h. Infusion of these cells followed by IL-2 administration may moderate a graft-versus tumor (GvT) effect in vivo. Sixteen patients--7 with non-Hodgkin's lymphoma (NHL), 2 with AML, 4 with multiple myeloma (MM), and 3 with Hodgkin's disease (HD)--received busulfan (4 mg/kg/day for 4 days) and cyclophosphamide (60 mg/kg/day for 2 days) or cyclophosphamide/TBI (1320 cGy). Autologous HSC were activated by culturing with IL-2 for 24 h before reinfusion. Subcutaneous administration of IL-2 began after engraftment at 1.8 x 10(6) IU/m2/day for 1-4 weeks. Neutrophil engraftment occurred on day 13.1 (median) (range 9-45 days), and platelet engraftment occurred on day 19.3 (median) (range 7-54 days) for 15 patients, with delayed engraftment observed in 3 patients. One patient experienced a fatal cardiac arrhythmia. Five patients developed transient skin rashes with histologic evaluation demonstrating findings consistent with GvHD. At 17 months (median) (range 7-23 months), 9 patients are alive, with 6 patients remaining disease free. This pilot trial demonstrates mild to moderate toxicities and a possible delay in platelet engraftment. Further trials will determine the optimal dose and duration of IL-2 therapy and possible impact of this therapy on survival. Laboratory investigations are evaluating the presence of autologous GvHD and a possible GvT effect.
authors.affiliation: Division of Hematology and Oncology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Meehan
authors.forename: A
authors.initials: A
authors.lastname: Badros
authors.forename: S R
authors.initials: SR
authors.lastname: Frankel
authors.forename: R
authors.initials: R
authors.lastname: Cahill
authors.forename: E
authors.initials: E
authors.lastname: Areman
authors.forename: M
authors.initials: M
authors.lastname: Jenson
authors.forename: R
authors.initials: R
authors.lastname: Sacher
authors.forename: A
authors.initials: A
authors.lastname: Mazumder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014182:Transplantation, Autologous
chemical_list: D007376:Interleukin-2