Allografting for Adult T-Cell Leukemia/Lymphoma: A Nationwide Retrospective Analysis.
Authors: Hishizawa Masakatsu , Kanda Junya , Utsunomiya Atae , Taniguchi Shuichi , Eto Tetsuya , Moriuchi Yukiyoshi , Tanosaki Ryuji , Kawano Fumio , Miyazaki Yasushi , Nagafuji Koji , Hara Masamichi , Yoshiba Fumiaki , Takanashi Minoko , Kai Shunro , Atsuta Yoshiko , Kawase Takakazu , Nagamura-Inoue Tokiko , Matsuo Keitaro , Kato Shunichi , Morishima Yasuo , Okamura Jun , Kodera Yoshihisa , Uchiyama Takashi 
Published: October 2019

Abstract
Background: Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm developing in a minority of individuals infected with human T-cell leukemia virus type I (HTLV-I). Although the results of conventional chemotherapy remain unsatisfactory for the management of ATL, allogeneic hematopoietic stem-cell transplantation (allo-SCT) is emerging as a promising alternative which can provide long-term remission in selected patients.
Methods: To evaluate the efficacy of allo-SCT for the treatment of ATL, data on 397 patients (pts) with ATL who had received allo-SCT between 01/1996 and 12/2005 were collected through JSHCT, JMDP and JCBBN. We analyzed pts who did not have a history of previous stem-cell transplantation; who received a T-cell-replete graft; who had data on age at transplantation, sex, donor type, stem-cell source, conditioning regimen, and graft-versus-host disease (GVHD) prophylaxis. A total of 363 pts, with a median age of 51 yrs (range, 18–79), 201 males and 162 females, fulfilled these criteria: 175 received bone marrow and/or peripheral blood from a related donor; 188 received marrow or cord blood from an unrelated donor. At the time of transplantation, 91 pts were in complete remission (CR) and 226 were not in CR. Risk factors which potentially affect the survival outcomes were analyzed using proportional-hazards models.
Results: The median follow-up was 21.6 months (range, 1.5–102). The unadjusted 3-year overall survival, disease-associated mortality, and treatment-related mortality (95% confidence interval [CI]) for pts in CR at transplantation were 48% (35–59%), 16% (8–27%), and 35% (24–45%), respectively, while those for pts not in CR were 22% (16–29%), 35% (28–42%), and 41% (34–48%), respectively. Multivariable analyses revealed four significant factors which adversely affected survival: older recipient age (>50 yrs)(adjusted hazard ratio [HR] 1.71; 95% CI, 1.24–2.38; P=0.001), male recipient (HR 1.46; 95% CI, 1.10–1.93; P=0.009), disease status other than CR (HR 2.21; 95% CI, 1.57–3.12; P<0.001), and donor type: HRs for death after allo-SCT using a family donor other than an HLA-matched sibling (n=45), an unrelated marrow donor (n=98), and an unrelated cord blood unit (n=90), as compared with an HLA-matched sibling (n=130), were 1.64 (95% CI, 1.05–2.55; P=0.028), 1.24 (95% CI, 0.85–1.80; P=0.26), and 1.85 (95% CI, 1.29–2.66; P=0.001), respectively. Among 156 pts who received allo-SCT not in CR and survived more than 30 days with sustained engraftment, development of grade I-II acute GVHD, as compared with absence of acute GVHD, was associated with a lower risk of death (HR 0.54; 95% CI, 0.34–0.86; P=0.01) in multivariable Cox models including the occurrence of acute GVHD as a time-dependent covariate.
Conclusions: Allo-SCT is effective therapy which confers long-term survival in a substantial proportion of patients with ATL but at the cost of significant treatment-related mortality. Favorable outcomes after developing mild acute GVHD in patients not in CR at transplantation suggest the presence of a graft-versus-ATL effect.