Minimal Residual Disease (MRD) in Adult T-Cell Leukemia/Lymphoma (ATLL) Evaluated by HTLV-1 Proviral Load and Soluble IL-2 Receptor Level in Peripheral Blood.

Abstract

Background: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type-1 (HTLV-1). Age, advanced PS, high LDH value, hypercalcemia and multiple visceral involvements were reported as prognostic factors for ATLL. Although initial therapy is often successful for aggressive ATLL with response rate of 50–80%, relapse (Rel) or progressive disease (PD) is frequent with 2 year-survival of 15–45% after chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). That means clinical evaluation of response is not sufficient to predict the prognosis of ATLL. HTLV-1 proviral load (PL) and soluble IL-2 receptor (sIL-2R) level have been reported to be associated with disease activity in ATLL.Method: We prospectively analyzed MRD in aggressive ATLL, acute(A)-, lymphoma(L)- or unfavorable chronic(C)-type, by measuring PL and sIL-2R level in peripheral blood, using real time PCR for Tax region of the virus and conventional ELISA, respectively.Results: PL and sIL2-R were measured just before start of therapy and every 2 months for 1 year unless Rel/PD happens in 78 pts. Median survival time was 7.3 months. Before chemotherapy (n=62), PL was high in order of C, A, and L, and sIL-2 level was of A, L and C, respectively. Neither PL nor sIL2-R level at first point was prognostic factor for pts having chemotherapy, while sIL2-R level, but not PL, was a prognostic factor in trend for pts having allo-HSCT (n=16). Median of the follow up for MRD was 4 months in the former and 6 months in the latter, respectively. In general, sequential data of both reflected disease activity in each case. PL and sIL-2R level were lower during complete response (CR) than partial response (PR), and elevated at Rel/PD. In cases with CR after chemotherapy, PL decreased gradually in 2 to 4 months and was still detected at levels of 1 to 10% during CR. In CR cases after HSCT, PL was often not detected (<0.2%) in 2 months, while sIL-2R level was still high probably reflecting GVHD activity. In CR cases with chemotherapy as compared to PR cases, increase in PL and/or sIL-2R level frequently preceded clinical relapse.Conclusions: These results in aggressive ATLL suggest that; 1) sIL2-R level, but not PL, was a potential prognostic factor for pts having HSCT. 2) PL was better than sIL-2R in estimation of MRD after HSCT. 3) Exacerbation of PL and/or sIL2-R was more useful for prediction of relapse in CR cases as compared to PR cases after chemotherapy.