INTERLEUKIN-2 WITH OR WITHOUT LYMPHOKINE-ACTIVATED KILLER-CELLS AS CONSOLIDATIVE IMMUNOTHERAPY AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATIONFOR ACUTE MYELOGENOUS LEUKEMIA

IL-2 with or without autologous lymphokine-activated killer (LAK) cell s, administered early after ABMT for AML may eradicate residual diseas e 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 l ater stage, in two separate trials. Patients with AML in first relapse (n = 9), second CR (n = 3) or second relapse (n = 2) underwent ABMT a fter busulfan (BU), CY and total body irradiation (n = 11) or BU/CY al one (n = 3), with marrow that was (n = 6) or was not (n = 8) purged wi th 4-HC. In a previously-reported Phase I trial, eight patients receiv ed IL-2 (Roche) by continuous infusion at 0.3-3.0 x 10(6) U/m2/day x 5 days and, after 6 days of rest, 0.3 x 10(6) U/m2/day X 10 days. In a subsequent trial, five patients received IL-2 at 3.0 x 10(6) U/m2/day x 5 days, underwent leukapheresis for 3 days and received their LAK ce lls plus IL-2 (0.3 x 10(6) U/m2/day x 10 days). A sixth patient receiv ed only 2 days of IL-2, developed sepsis and died of multiorgan failur e. All other patients had mild to moderate toxicity which was reversib le. All patients developed neutrophilia, lymphocytosis and thrombocyto penia. IL-2 with or without LAK therapy was initiated 21-91 days (medi an 51 days) after ABMT. Severe thrombocytopenia (< 10 x 10(9)/l) occur red 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 AB MT. The actuarial probability of relapse for the 14 patients is 23% (c onfidence 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 thrombocytop enia, (2) IL-2 with or without LAK cell therapy early after ABMT for A ML may decrease the relapse rate, and (3) a prospectively randomized t rial of IL-2 versus no IL-2 after ABMT for such AML patients is warran ted.