Adult T-cell Leukemia (ATL) is an aggressive malignant disease of CD4+ T-cells associated with human
T-cell leukemia virus type I (HTLV-I). Prognosis of ATL patients is directly correlated to the subtype of ATL. Treatment of the aggressive forms (acute and
lymphoma types) of ATL remains inadequate, as most ATL patients receive conventional
chemotherapy without stem cell rescue. At present, LSG15 is the standard
chemotherapy for the treatment of aggressive ATL, but the efficacy of LSG15 in most patients is transient. To prolong median survival time, additional
therapies for maintenance of complete response (CR) are needed after achieving CR by
induction chemotherapy. Improved outcome after allogeneic
stem cell transplantation (allo-SCT), despite a high incidence of
graft-versus-host disease, has been reported. Thus, allogeneic
bone marrow transplantation and allogeneic peripheral blood SCT may have great potential for eradication of HTLV-1 and cure of ATL. Recently, reduced-intensity conditioning
stem cell transplantation was also reported to be effective for ATL. Although several issues, including selection criteria for patients and sources of stem cells remain to be resolved, allo-SCT may be considered as a treatment option for patients with aggressive ATL. To evaluate whether allo-SCT is more effective than the standard
chemotherapy (LSG15) for aggressive ATL, an up front phase II clinical trial of JCOG-LSG is now being planned. Novel innovative targeted strategies, such as antiretroviral
therapy,
arsenic trioxide,
nuclear factor-kappaB inhibitors, proteasome inhibitors, histone deacetylase inhibitors, several
monoclonal antibodies including anti-
CC chemokine receptor 4, anti-
folate,
purine nucleotide phosphorylase inhibitor, mTOR (
mammalian target of rapamycin) inhibitor,
bendamustine, small molecule Bcl-2 inhibitors and Tax-targeted
immunotherapy, should be promptly studied in order to develop curative treatments for ATL in the near future.