Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor

Abstract

Summary. Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhlL-2 was 26 weeks (range 2-44). Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen. Relapse leukaemic cells from three of four patients expressed the α chain of the IL-2 receptor as assessed by flow cytometry. After overnight incubation and removal of T-lymphocytes the proportion of cells from these patients expressing the α chain increased from 15% to 61% (P < 0·01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL-2 receptor α chain proliferated in response to 1000 u/ml of rhIL-2 in vitro, with a stimulation index > 1·95 (P < 0·05). Following rhIL-2 immunotherapy for AML, relapse cells may express an inducible form of the a chain of the IL-2 receptor, which can mediate a proliferative response. It is possible that rhIL-2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.