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Peripheral Blood and Bone Marrow Immunophenotypic and Functional Modifications Induced in Acute Leukemia Patients Treated with Interleukin 2: Evidence of in Vivo Lymphokine Activated Killer Cell Generation¹

Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Clinica Medica, University of Torino, and Dipartimento di Biopatologia Umana, Sezione di Ematologia, University of Rome, Italy

The effect of treatment with interleukin 2 (IL2) on the phenotypic and functional immune system of acute leukemia patients was investigated. Fifteen acute myeloid leukemia and acute lymphoid leukemia patients with evidence of persistent disease were further subdivided into two groups according to the percentage of bone marrow (BM) blasts: group a had 6–15% blasts and group b had 30–65%. Following two cycles of IL2 (Glaxo Imb, Geneva, Switzerland) given i.v. by continuous infusion at escalating doses, no major changes in the proportion of CD3-, CD4-, and CD8-positive cells were encountered in the blood or in the marrow of either group of patients. When these could be retested after four cycles of IL2, a significant increase of CD3+ and CD4+ cells was documented in the peripheral blood (PB), as well as a significant increase of CD3+ cells in the BM. Irrespective of the number of cycles administered, the proportion of CD16+ cells increased significantly in the blood in both groups of patients and in the marrow of group a patients only. The expression of CD25 was significantly enhanced in all samples tested.

Following IL2 administration, an enhancement of the natural killer compartment was documented. This was consistently more evident in patients with more limited disease. A significant amplification of the in vitro-induced lymphokine-activated killer function was noted in the BM of the treated patients. Furthermore, we documented the presence both in the PB and in the BM of "spontaneous" lymphokine-activated killer cells generated in vivo following IL2 administration.

These results demonstrate that in acute leukemia of both myeloid and lymphoid origin, treatment with IL2 is capable of inducing profound immunophenotypic and functional modifications in PB and in BM lymphocytes, particularly in patients with more limited disease. The evidence of the in vivo activation of cytotoxic cells, particularly in the BM, may help to explain the clinical responses preliminarily observed in individual acute leukemia patients.

¹ This work was supported by Istituto Superiore di Sanita', Italy-United States Program on "Therapy of Tumors," Rome, and by Ministero della Pubblica Istruzione, Rome. A. G. T. is in receipt of a fellowship from Associazione Italiana per la Ricerca sul Cancro, Milan.

² To whom requests for reprints should be addressed, at Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Clinica Medica, University of Torino, Via Genova 3, 10126 Torino, Italy.

Received 8/ 9/90. Accepted 11/ 6/90.