Interleukin-2 with or without lymphokine-activated killer cells as consolidative immunotherapy after autologous bone marrow transplantation for acute myelogenous leukemia
Benyunes, M.C.; Massumoto, C.; York, A.; Higuchi, C.M.; Buckner, C.D.; Thompson, J.A.; Petersen, F.B.; Fefer, A.
Bone Marrow Transplantation 12(2): 159-163
ISSN/ISBN: 0268-3369 PMID: 8401364 Accession: 008899061
IL-2 with or without autologous lymphokine-activated killer (LAK) cells, administered early after ABMT for AML may eradicate residual disease and reduce relapses. This paper reports 14 patients who received IL-2 or IL-2 plus LAK cells after ABMT for AML in first relapse or at a later stage, in two separate trials. Patients with AML in first relapse (n = 9), second CR (n = 3) or second relapse (n = 2) underwent ABMT after busulfan (BU), CY and total body irradiation (n = 11) or BU/CY alone (n = 3), with marrow that was (n = 6) or was not (n = 8) purged with 4-HC. In a previously reported Phase I trial, eight patients received IL-2 (Roche) by continuous infusion at 0.3-3.0 times 10-6 U/m-2/day times 5 days and, after 6 days of rest, 0.3 times 10-6 U/m-2/day times 10 days. In a subsequent trial, five patients received IL-2 at 3.0 times 10-6 U/ml/day times 5 days, underwent leukapheresis for 3 days and received their LAK cells plus IL-2 (0.3 times 10-6 U/ml/day times 10 days). A sixth patient received only 2 days of IL-2, developed sepsis and died of multiorgan failure. All other patients had mild to moderate toxicity which was reversible. All patients developed neutrophilia, lymphocytosis and thrombocytopenia. IL-2 with or without LAK therapy was initiated 21-91 days (median 51 days) after ABMT. Severe thrombocytopenia ( lt 10 times 10-9/l) occurred during the apheresis days. Three patients relapsed at 4, 5 and 10 months, while ten remain in CR 13+ to 48+ (median 34+) months after ABMT. The actuarial probability of relapse for the 14 patients is 23% (confidence interval (CI) = 12-34%) and the probability of disease-free survival is 71% (CI = 59-83%). The results suggest that: (1) LAK cells cannot be used in these patients because of unacceptable thrombocytopenia, (2) IL-2 with or without LAK cell therapy early after ABMT for AML may decrease the relapse rate, and (3) a prospectively randomized trial of IL-2 versus no IL-2 after ABMT for such AML patients is warranted.