Safety and Efficacy of Donor Lymphocyte Infusions following Mismatched Stem Cell Transplantation

• Published in: Biology of blood and marrow transplantation Vol. 12; no. 12; pp. 1295 - 1301
• Main Authors: Or, R., Hadar, E., Bitan, M., Resnick, I.B., Aker, M., Ackerstein, A., Samuel, S., Tsirigotis, P., Gesundheit, B., Slavin, S., Shapira, M.Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2006
• Subjects: Acute Disease; Adolescent; Adult; Child, Preschool; Donor lymphocyte infusion; Feasibility Studies; Female; Graft Enhancement, Immunologic - statistics & numerical data; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Graft vs Leukemia Effect; Graft-versus-host disease; Graft-versus-leukemia effects; Histocompatibility; HLA Antigens - immunology; Humans; Kaplan-Meier Estimate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - surgery; Leukemia, Myeloid - mortality; Leukemia, Myeloid - surgery; Leukocyte Reduction Procedures; Lymphocyte Transfusion - adverse effects; Lymphoma - surgery; Male; Middle Aged; Mismatched; Myelodysplastic Syndromes - surgery; Peripheral Blood Stem Cell Transplantation - statistics & numerical data; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - surgery; Remission Induction; Stem cell transplantation; Survival Analysis; Tissue Donors; Transplantation Conditioning; Tumor Burden; Graft-versus-host disease; Stem cell transplantation; Graft-versus-leukemia effects; Mismatched; Donor lymphocyte infusion
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2006.07.014

The use of a mismatched allograft necessitates T cell depletion for prevention of uncontrolled graft-versus-host disease (GVHD), thus impairing a graft-versus-leukemia effect. Data on donor lymphocyte infusion (DLI) after mismatched stem cell transplantation are lacking. Our experience with 28 patients (treated with 59 mismatched DLIs; range, 1-7) is described. The procedure was prophylactic in 6 patients (9 DLIs) and therapeutic in 22 (50 DLIs). DLI dose ranged from 10 2 to 1.5 × 10 9 T cells/kg. In the 6 patients receiving prophylactic DLI, complete remission was maintained in 5; however, 2 died from GVHD. Clinical response to therapeutic DLI was seen in 6 of 22 (27.3%) patients; a greater tumor burden produced a lower response. GVHD appeared in 13 of 28 patients. Surprisingly, a greater HLA mismatch was associated with a lower risk of GVHD, with 3 of 19 DLIs in 3/6 matching and 16 of 29 DLIs in 5/6 matching with similar follow-up. Nevertheless, no correlation between efficacy and HLA mismatching was noted. Death was frequent and usually related to the basic disease rather than to DLI complications. We conclude that mismatched DLI is feasible and may be effective, especially if given soon after transplantation. Future developments using cell therapy with selective or targeted anticancer activity are warranted, with special attention to prophylactic treatment of T cell depleted mismatched allografts recipients.