ASSESSMENT OF THERAPEUTIC POTENTIAL OF INTERLEUKIN-2 FOR MYELODYSPLASTIC SYNDROMES

The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic s yndromes (MDS) was evaluated in vitro. IL-1-induced lymphokine-activat ed killer (Wt) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lin es and MDS blasts was significantly reduced in high-risk MDS (refracto ry anaemia with excess blasts (RAEB), RAEB in transformation, and leuk aemic transformation of MDS), but was relatively well-preserved in low -risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). E xamination of the immunophenotypes of freshly-isolated lymphocytes sho wed that the percentage of CD4+ cells in low-risk MDS and the percenta ge of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was signif icantly reduced compared with these populations in normal subjects. Af ter cultivation with IL-2, these three cell populations were still red uced in the corresponding MDS groups and the percentage of CD3-CD56+ c ells were significantly reduced in highrisk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cell s and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in pa rt, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high- risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.