Effect of low-dose interleukin-2 on disease relapse after T-cell-depleted allogeneic bone marrow transplantation.
T-cell depletion of donor bone marrow has been associated with an increased risk of disease relapse after allogeneic bone marrow transplantation (BMT). Recombinant interleukin-2 (IL-2), which is capable of increasing the antileukemic activity of peripheral blood lymphocytes obtained from patients who have undergone BMT, has been proposed as a potentially useful agent to reduce the risk of relapse post-BMT. We have previously shown that IL-2 administered to patients at very low doses after BMT is both clinically tolerable and immunologically active. We now report on the clinical outcome of 29 patients treated with low-dose IL-2 after CD6-depleted allogenic BMT for hematologic malignancy. IL-2 was administered by continuous infusion for up to 3 months beginning at a median of 67 days post-BMT. Eligibility requirements for IL-2 therapy included demonstration of stable engraftment and absence of acute grade 2-4 graft-versus-host disease (GVHD). Low-dose IL-2 was well tolerated by the majority of patients, with only 4 of 29 subjects withdrawn early. Acute GVHD developed in only one individual. After 12 weeks of treatment, the mean number of circulating natural killer cells in patients increased 10-fold without any significant change in T-cell number. Of the 25 patients who received > or = 1 month of IL-2, only 6 have relapsed. Relapse rate and disease-free survival (DFS) were determined in the 25 patients who completed at least 4 weeks of IL-2 treatment and compared with historical controls transplanted at our institution for the same conditions and treated with an identical ablative regimen and method of T-cell depletion. Only control patients who had survived disease free for 100 days post-BMT were included in this analysis. Cox's proportional hazards regression model suggested that, compared with control patients without a history of GVHD, patients treated with IL-2 had a lower risk of disease relapse (hazard ratio 0.34; range, 0.14 to 0.82) and superior DFS (hazard ratio 0.39; range 0.18 to 0.87). A randomized controlled trial of IL-2 immunotherapy after T-cell-depleted BMT should now be undertaken.
Soiffer
R J
RJ
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Murray
C
C
Gonin
R
R
Ritz
J
J
D000328:Adult; D000367:Age Factors; D016026:Bone Marrow Transplantation / Q000379:methods*; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000601:surgery / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery / Q000628:therapy; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D008228:Lymphoma, Non-Hodgkin / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2