Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. The aggressive type is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent cases, that is, smoldering ATL, the median survival time is 55.0 months. Natural killer (NK) cells have T-cell-like memory functions, especially in viral infections. We treated patients with ATL and its related diseases with ANK therapy, in which NK cells from the patient’s blood were expanded and amplified ex vivo and infused back into the patient. Case presentation: ANK therapy was administered to five patients, including one with acute crisis and one with HTLV-1-associated bronchioloalveolar disease (HABA).

Even in these cases of smoldering leukemia with acute crisis and HABA, their condition improved with ANK therapy, leading to complete remission (CR).

Three of these cases were in watchful waiting but had skin lesions. In the case of smoldering leukemia with acute crisis, multiple erythema was observed, and high soluble IL-2 receptor (sIL-2R) levels were elevated. The case of smoldering leukemia with HABA showed dyspnea and a decrease in pulmonary function, and a CT scan showed signs of HABA. After the ANK therapy, the five patients achieved CR and maintained CR with no other supportive care required. The NK activity of the two smoldering leukemia patients showed a higher value compared to that of healthy controls even after a long period of time. These results indicate the possibility that ANK cells kill ATL cells and/or improve the dysregulation of the cytokine network induced by the ATL cells by inducing a memory-like NK function and maintaining high NK activity to prevent the risk of the relapse.