B. Wörmann

Interleukin-2 Postremission Therapy in Acute Myeloid Leukemia (AML): In Vitro and In Vivo Effects of a Five Day Continuous Infusion of IL-2 on Phenotype and Function of Peripheral Lymphocytes

In vitro studies have demonstrated the anti-leukemic effect of IL-2 stimulated cytotoxic lymphocytes on allogeneic leukemic blasts prompting clinical trials with IL-2 in vivo. We initiated a phase II study with IL-2 in 6 patients with acute myeloid leukemia. The patients were in second or third remission after successful salvage treatment for relapse. All patients had received a standardized first line treatment according to the protocol of the German AML cooperative group. Salvage treatment consisted of sequential high dosed cytosine-arabinoside and mitoxantrone (sHAM). the postremission IL-2 therapy consisted of continuous intravenous infusion of IL-2 in a dosis of 3 × 106 IU/m/day over 5 days, four weeks later the next cycle was given. Lymphocyte subsets in the peripheral blood and their IL-2 receptor expression of these patients were studied on day 0, 2 and 5 of the IL-2 cycle using multiparameter flow cytometry. 13 IL-2 cycles in 6 patients were analysed.

Assessment of Lymphokine-Activated Killer Activity Against Myeloid Leukemic Blasts and the Myeloid Cell Line K562 by Flow Cytometry

It is well known that recombinant interleukin-2 (rIL-2) and other lymphokines can be used to increase cell mediated cytotoxicity of PBL against non-HLA restricted targets. Futhermore rIL-2 is able to induce cell mediated cytotoxicity of PBL against tumor cells which were first insensitive to cell mediated cytotoxicity. These activated lymphocytes are called lymphokine-activated-killer (LAK) cells. It is of great importance to determine the functional capacities of these activated cells for killing specific target cells like leukemic blasts. In this study we determined the functional capacity of activated killer cells from healthy donors for killing blasts from acute myeloid leukemia (AML) patients and compared it with the capacity for killing K562 cells. We use newly developed flow cytometric assays for determination of cytotoxicity [1] and conjugate formation. In this way we obtain information on whether leukemia related defects in the killing mechanism occur and to what extent it is possible to overcome these defects by using specific cytokines.