title: Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning.
abstract: This study retrospectively analyzed data from 446 patients given hematopoietic cell transplants from HLA-matched related or unrelated donors after conditioning with 2 Gy total body irradiation with or without fludarabine and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine following grafting. Fifty-three of 446 patients received donor lymphocyte infusion (DLI) with a median CD3 dose of 1 x 10(7) cells/kg. Their diagnoses included myelodysplastic syndrome (n = 10), acute leukemia (n = 10), chronic leukemia (n = 11), multiple myeloma (n = 9), lymphoma (n = 9), and solid tumors (n = 4). Patients received DLI for persistent disease (n = 8), disease relapse (n = 17), progressive disease (n = 12), low donor chimerism with disease (n = 11), or low chimerism with disease remission (n = 5). Seventeen of the 53 patients (32%) are alive with a median follow-up of 30 months; 5 are in complete remission (CR), 2 are in partial remission (PR), and 10 have stable or progressive disease. Nine of 53 patients (17%) developed grades II to IV acute graft-versus-host disease. Of 48 patients receiving DLI for treatment of disease, 7 achieved CR and 5 PR, with an overall response rate of 25%. Six of 16 patients who received DLI for chimerism had increases in donor chimerism leading to sustained engraftment, whereas 10 eventually rejected their grafts. In conclusion, DLI is a potential treatment strategy, with acceptable toxicity, for patients with persistent, relapsed, or progressive disease after nonmyeloablative hematopoietic cell transplantation.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109, USA.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Monic J
authors.initials: MJ
authors.lastname: Stuart
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.forename: Ed
authors.initials: E
authors.lastname: Agura
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002678:Chimera; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016219:Immunotherapy, Adoptive; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous