INTERLEUKIN-2+ -LYMPHOCYTES AS CONSOLIDATIVE IMMUNOTHERAPY AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR HEMATOLOGIC MALIGNANCIES/

Patients who undergo autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies experience a high relapse rate. The rapy with interleukin-2 (IL-2)+/-lymphokine-activated killer (LAK) cel ls has induced clinical responses in some patients with advanced malig nant lymphoma (ML) or acute myelogenous leukemia (AML). It is postulat ed that IL-2+/-LAK cells represents a potentially non-cross-resistant therapeutic modality which might prevent or delay relapses if used as consolidative immunotherapy after ABMT, at a time of minimal residual disease. Therefore, we first studied the reconstitution of IL-2-respon sive LAK precursor cells after ABMT and found them in the circulation as early as 3 weeks after ABMT. A phase Ib clinical trial was then per formed which identified a tolerable IL-2 regimen which could be admini stered early after ABMT and which could induce immunomodulatory effect s. We then initiated a clinical trial to determine the feasibility of generating and administering autologous LAK cells using this IL-2 regi men after ABMT for 16 patients with ML. The results show that IL-2+LAK therapy early after ABMT is feasible but is more toxic than IL-2 alon e. Patients with AML on the phase I IL-2 trial and with ML on the IL-2 +LAK protocol were evaluated for tumor status. Of 8 patients with AML in first relapse or at a later stage who underwent ABMT and received I L-2, 2 have relapsed, while 6 remain in complete remission 26+ to 40(median 28+) months after ABMT. Of 16 patients with ML considered at h igh risk for relapse who were treated with ABMT+IL-2+LAK, 5 have relap sed, while 11 remain in complete remission at 6+ to 21+ (median 10+) m onths after ABMT. The results in both trials are quite encouraging and appear to be better than those in nonrandomized historical controls a t our institution. Prospectively randomized trials of IL-2 versus no I L-2 after ABMT in such patients are being initiated to assess definiti vely the effect, if any, on the relapse rate.