Adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma
Classification and external resources
Specialty
ICD-10	C83-C88
ICD-9-CM	204.0-208.9
ICD-O	M9827/3
DiseasesDB	29486
Patient UK	Adult T-cell leukemia/lymphoma
MeSH	D015459

Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's own T-cells.

Human T cell leukemia/lymphotropic virus type 1 (HTLV-1) is believed to be the cause of it, in addition to several other diseases.

Signs and symptoms

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. Circulating lymphocytes with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-1 causes ATL. This evidence includes the frequent isolation of HTLV-1 from patients with this disease and the detection of HTLV-1 proviral genome in ATL leukemic cells. ATL is frequently accompanied by visceral involvement, hypercalcemia, skin lesions, and lytic bone lesions. Bone invasion and osteolysis, features of bone metastases, commonly occur in the setting of advanced solid tumors, such as breast, prostate, and lung cancers, but are less common in hematologic malignancies. However, patients with HTLV-1–induced ATL and multiple myeloma are predisposed to the development of tumor-induced osteolysis and hypercalcemia. One of the striking features of ATL and multiple myeloma induced bone disease is that the bone lesions are predominantly osteolytic with little associated osteoblastic activity. 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. 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.

Treatment

Treatment options that have been tried include zidovudine and the CHOP regimen. Pralatrexate has also been investigated. Most therapy is directed towards the cancer rather than the virus itself. 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.

Recently, mogamulizumab, has been approved for the treatment of ATL in Japan.

At a medical conference in December 2013, researchers reported anywhere from 21-50% of ATL patients have disease expressing CD30. This suggests treatment with CD30-targeting brentuximab vedotin may be beneficial.

Epidemiology

HTLV-1 infection in the United States appears to be rare. Although little serologic data exist, 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 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 in Africa.

ATL is relatively uncommon among those infected with HTLV-1. The overall incidence of ATL is estimated at about 1 per 1,500 adult HTLV-1 carriers per year. Those cases that have been reported have occurred mostly among persons from the Caribbean or blacks from the Southeast (National Institutes of Health, unpublished data). There appears to be a long latent period between HTLV-1 infection and the start of ATL.

Research

Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation. Pralatrexate is one compound currently under investigations for the treatment of PTCL.

In pregnancy

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. How it is handled depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.

External links

• Genoveffa Franchini's NCI page: Human Retroviral Diseases: Pathogenesis and Prevention
• International Retrovirology Association