[6] However, cases have increased in non-endemic regions with highest incidence of HTLV-1 in southern/northern islands of Japan, Caribbean, Central and South America, intertropical Africa, Romania, northern Iran.

Beyond clinical trials, treatments are centered on multiagent chemotherapy, zidovudine plus interferon a (AZT/IFN), and allogenic hematopoietic stem cell transplantation (alloHSCT).

[6] ATL is usually a highly aggressive non-Hodgkin's lymphoma with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell phenotype.

In patients with 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.

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.

[13] 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.

[16] 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.

Those cases that have been reported have occurred mostly among persons from the Caribbean or African Americans from the Southeast United States (National Institutes of Health, unpublished data).