Abstract
The prognosis of aggressive adult T-cell leukemia-lymphoma (ATL) remains poor because of frequent infections and drug resistance. Dose-intensified chemotherapy followed by autologous stem cell transplantation failed to improve the prognosis of patients with ATL; however, we first revealed that allogeneic hematopoietic cell transplantation (allo-HCT) might improve their prognosis. We showed that reduced-intensity stem cell transplantation using peripheral blood was feasible for elderly patients. Further, the prognosis of patients in remission, who receive cord blood transplantation, has been recently improved and is equivalent to that of patients who receive transplants from other stem cell sources. As for the timing of HCT, the patients who underwent transplantation early showed better outcomes than those who underwent transplantation late. Based on the analysis of patients with aggressive ATL, including those who received transplants, we identified five prognostic factors for poor outcomes: acute-type ATL, poor performance status, high soluble interleukin-2 receptor levels, hypercalcemia, and high C-reactive protein level. Next, we developed a new prognostic index: the modified ATL-PI. The overall survival (OS) rates were significantly higher in patients who underwent allo-HCT than those who did not in the intermediate and high-risk groups stratified using the modified ATL-PI. Two new anti-cancer agents, mogamulizumab and lenalidomide, were recently approved for ATL patients in Japan. They are expected to induce longer survival in ATL patients when administered along with transplantation. However, a retrospective analysis that the risk of severe, acute, and corticosteroid-refractory graft-versus-host disease was higher in patients who received mogamulizumab before allo-HCT, and that mogamulizumab might increase the transplant-related mortality (TRM) rates and decrease the OS rates compared to those of patients who did not receive mogamulizumab. However, our recent study showed that administration of mogamulizumab before allo-HCT tended to improve the survival of patients with ATL. In conclusion, allo-HCT procedures for patients with aggressive ATL have considerably progressed and have helped improve the prognosis of these patients; however, many concerns still remain to be resolved. Further development of allo-HCT by using new molecular targeting agents is required for the improvement of cure rates in patients with ATL.
Highlights
Adult T-cell leukemia-lymphoma (ATL) is an intractable peripheral T-cell malignancy caused by human T-cell leukemia virus type-I (HTLV-1)
The rates of ATL-related death were not different in both the groups, but the transplant-related mortality (TRM) rates were significantly higher in late transplant patients than in early transplant ones. These results suggest that early transplant is required for better outcomes for patients with ATL in good performance status (PS) because ATL cells are resistant to anti-cancer agents (Kuwazuru et al, 1990; Ohno et al, 2001a,b); persistent chemotherapy deteriorates patients’ conditions without obtaining complete remission (CR)
We proposed the appropriate use of mogamulizumab for patients with aggressive ATL before allo-HCT as follows: (1) mogamulizumab should not be administered to patients with aggressive ATL who plan to undergo transplantation if patients can obtain CR or partial remission (PR) without mogamulizumab; (2) mogamulizumab should be administered a few times only when patients cannot obtain remission by ordinary combination chemotherapy; (3) allo-HCT should be recommended with at least 50-day interval, if possible, between last mogamulizumab administration and transplant, and (4) no consensus about graft-versus-host disease (GVHD) prophylaxis, choice of stem cell source and prophylaxis for infectious diseases (Fuji et al, 2018a)
Summary
Adult T-cell leukemia-lymphoma (ATL) is an intractable peripheral T-cell malignancy caused by human T-cell leukemia virus type-I (HTLV-1). Dose-intensified chemotherapy followed by autologous stem cell transplantation failed to improve the prognosis of patients with ATL because of high ATL relapse rates and frequent infectious complications (Asou et al, 1985; Tsukasaki et al, 1999). The successful treatment of a patient with aggressive ATL with allogeneic hematopoietic cell transplantation (allo-HCT) was reported in 1987. In 2001, we first reported the possibility of improved outcomes in patients with aggressive ATL by using allo-HCT (Utsunomiya et al, 2001). The prognosis of patients with aggressive ATL improved by allo-HCT, transplant-related mortality (TRM) rates in patients who received transplantation with myeloablative conditioning (MAC) regimen were very high (Utsunomiya et al, 2001; Kami et al, 2003; Fukushima et al, 2005). The prognosis of patients with ATL who underwent cord blood transplantation (CBT) was poorer than that of patients transplanted with other stem cell sources, it has recently improved (Hishizawa et al, 2010; Nakamura et al, 2012; Fukushima et al, 2013; Kato et al, 2014)
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