Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

Author:

Bethge Wolfgang A.1,Hegenbart Ute1,Stuart Monic J.1,Storer Barry E.1,Maris Michael B.1,Flowers Mary E. D.1,Maloney David G.1,Chauncey Thomas1,Bruno Benedetto1,Agura Ed1,Forman Stephen J.1,Blume Karl G.1,Niederwieser Dietger1,Storb Rainer1,Sandmaier Brenda M.1

Affiliation:

1. From the Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington, Seattle; University of Leipzig, Leipzig, Germany; Stanford University, Stanford, CA; Veterans Administration Medical Center, Seattle, WA; University of Torino, Torino, Italy; Baylor University, Dallas, TX; and City of Hope National Medical Center, Duarte, CA.

Abstract

AbstractThis 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 × 107 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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