ATL, elevated serum levels of IL-1, TGFβ, PTHrP, macrophage inflammatory protein (MIP-1α), and receptor activator of nuclear factor-κB ligand (RANKL) have been associated with hypercalcemia. Immunodeficient mice that received implants with leukemic cells from patients with ATL or with HTLV-1–infected lymphocytes developed hypercalcemia and elevated serum levels of PTHrP. Most patients die within one year of diagnosis. Infection with HTLV-1, like infection with other retroviruses, probably occurs for life and can be inferred when antibody against HTLV-1 is detected in the serum. Transmission Transmission of HTLV-1 is believed to occur from mother to child; by sexual contact; and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles. Diagnosis Diagnosis is made based on the combination of clinical features, characteristic morphologic and immunophenotypic changes of malignant cells. As clinical features and prognosis can be diverse, the disease is subtype-classified into four categories according to the Shimoyama classification: acute, lymphoma, chronic, smoldering. Normally, identification of at least 5 percent of tumor cells in peripheral blood and confirmation of human T-lymphotropic virus type-1 are sufficient for diagnosis of acute, chronic, and smoldering types. For the lymphoma type, histopathologic examination by biopsy of lymph nodes may be needed. Treatment Treatment options that have been tried include zidovudine and the CHOP regimen. Pralatrexate has also been investigated. Recently, it has been reported that the traditional glucocorticoid-based chemotherapy toward ATL are largely mediated by thioredoxin binding protein-2 (TBP-2/TXNIP/VDUP1), suggesting the potential use of a TBP-2 inducer as a novel therapeutic target. In 2021, mogamulizumab was approved for relapsed/refractor treatment of ATL in Japan. At a medical conference in December 2013, researchers reported anywhere from 21 to 50% of ATL patients have disease expressing CD30. Although not FDA approved, treatment with CD30-targeting brentuximab vedotin in CD 30+ cases may be beneficial and supported by current NCCN guidelines. Epidemiology HTLV-1 infection in the United States appears to be rare. Although little serologic data exist, the prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey, and a rate of 49% has been found in a similar group in New Orleans. It is possible that the prevalence of infection is increasing in this risk group. Studies of HTLV-1 antibody indicate that the virus is endemic in southern Japan, in the Caribbean, South America, and