Role of Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia in an HTLV-1 Non-Endemic Area of Japan.
Authors: Shigematsu Akio , Tanaka Junji , Kobayashi Naoki , Yasui Hiroshi , Shindo Motohiro , Kakinoki Yasutaka , Yasutaka Kakinoki , Iyama Satoshi , HIroyuki Kuroda , Yutaka Tsutsumi , Hashino Satoshi , Imamura Masahiro , Teshima Takanori 
Published: October 2019

Abstract
Abstract 3089
Adult T-cell leukemia/lymphoma (ATL) mainly occurs in HTLV-1 endemic areas such as the southwest island in Japan (Kyushu) and Caribbean countries. A recent report showed that the incidence of ATL was increasing in HTLV-I non-endemic areas (1). Although allogeneic stem cell transplantation (allo-SCT) has been considered to be the only curative treatment for ATL (2, 3), there has been no report about the treatment strategy for ATL occurring in HTLV-1 non-endemic area. We therefore conducted a retrospective analysis for all of the patients who developed ATL and received allo-SCT in an HTLV-1 non-endemic area of Japan, Hokkaido (a northernmost island).
Clinical data for 56 patients who received allo-SCT were collected from 12 SCT centers in Hokkaido, Japan. The median age of the patients was 57 years (range: 37 – 69 years). Twenty-eight of the patients had acute type and 22 had lymphoma type. Median count of white blood cells and median levels of serum LDH and serum soluble interleukin-2 receptor (sIL-2R) at diagnosis were 10900/mL, 352 IU/L and 11153 mg/dL, respectively. After chemotherapies mainly using CHOP or VCAP–AMP–VECP regimens, twenty-three of the patents received allo-SCT in complete remission (CR), and the other patients received allo-SCT in non-CR (partial remission, n=16; primary refractory, n=9; relapse, n=23). Median levels of serum LDH and sIL-2R before the conditioning regimen were 218 IU/L and 1153 mg/dL, respectively. HCT-CI scoring was available in 42 of the patients, and the scores were 0 in 15 patients, 1 in 10 patients, 2 in 5 patients and more than 3 in 9 patients. Thirty-nine of the patients received bone marrow, 11 of the patients received peripheral blood stem cells and 6 of the patients received cord blood. Thirty of the patients received SCT from HLA-matched siblings, 22 of the patients received SCT from HLA-matched unrelated donors and 14 of the patients received SCT from HLA-mismatched donors. Seventeen patients received myeloablative conditioning and the other 39 patients received reduced-intensity conditioning. Fifty-three (95%) of the patients achieved neutrophil engraftment at median day of 16. Acute graft-versus-host disease (AGVHD) and grade II-IV AGVHD occurred in 40 (75%) and 31 (58%) evaluable patients, respectively, at median onset day of 29. Chronic GVHD (CGVHD) occurred in 24 (38%) evaluable patients at the median onset day of 168. After a median follow-up period of 48 months, 1-year overall survival (OS) and 5-year OS rates were 56.3% and 46.5%, respectively The survival curve reached a plateau at 22 months after SCT. Univariate analysis showed that year in which SCT was performed, male sex, high level of sIL-2R both at diagnosis and at SCT, and disease status (non-CR at SCT) were significant risk factors for overall survival. SIL-2R at SCT (P=0.02) was determined to be a significant risk factor for disease progression and male sex was marginally significant (P=0.06) by univariate analysis. Non-CR at SCT was marginally significant for transplant-related mortality (P=0.07). Worse survival for male patients and patients in non-CR at SCT were confirmed by using multivariate analysis with Cox's regression model [hazard ratio of 3.15 (95% confidence interval: 1.36–7.30) for male patients and hazard ratio of 2.70 (95% confidence interval: 1.01–7.24) for non-CR patients].
This is the first report on ATL patients in a non-endemic area who received allo-SCT, and we think that this report shows very important information for management of ATL patients in non-endemic areas.

Disclosures:
No relevant conflicts of interest to declare.