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Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm. A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development. ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularity be aggressive with poorer prognosis.

Current treatment regiments for ATL are based on clinical subtype and response to initial therapy. Some therapy modalities for treatment may not available in all countries therefore strategies differ across the world. All patients are referred to clinical trials if available. Beyond clinical trials, treatments are centered on multiagent chemotherapy, zidovudine plus interferon a (AZT/IFN), and allogenic hematopoietic stem cell transplantation (alloHSCT).

Globally, the retrovirus HTLV-1 is estimated to infect 20 million people with the incidence of ATL approximately 0.05 per 100,000 with endemic regions such as regions of Japan, as high as 27 per 100,000. 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. ATL normally occurs around the age of 62 years but median age at diagnosis does depend on prevalence of the HTLV-1 infection in the geographic location.

Contents

 * 1Signs and symptoms
 * 2Transmission
 * 3Diagnosis
 * 4Treatment
 * 5Epidemiology
 * 6Research
 * 7References
 * 8Further reading
 * 9External links

Signs and symptoms[edit]
ATL is a rare aggressive peripheral T- cell neoplasm that is associated with HTLV-1. 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.[citation needed]

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.

Multilobed nuclei that are "flower-like" or cerebriform in appearance in flow cytometry support diagnosis of ATL. Additionally, detection of HTLV-1 by ELISA and western blot confirmation is essential for diagnosis. Genomic changes are complex therefore, there is no single characteristic marker to contribute to diagnosis.

Due to variable clinical course, patients are classified by the Shimoyama Classification into different subtypes of ATL. Categorization is based on cell counts, LDH levels, calcium levels and sites of organ involvement.

Treatment:

Multi agent chemotherapy options include follow combination

VCAP-AMP-VECP (vincristine, cyclophosphamide, doxorubicin, and prednisone; doxorubicin, ranimustine, and prednisolone; and vindesine, etoposide, carboplatin, and prednisolone); CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone); etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (EPOCH); CHOEP (cyclophosphamide, vincristine, doxorubicin, etoposide, and prednisolone); dose-adjusted EPOCH; or hyper CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose methotrexate and cytarabine)

2/3 - Epidemiology of disease

4- genetic pathophysiology, low incidence of HTLV infected individuals to malignancy, gene sequencing (Kataoka)

2- 2009 guidelines and 2019 updates(cook)

ishida- combination chemo with mogamulizumab, phase 2 clinical trial

Ishitsuka- treatment

Matutes/ Hermine - AZT + IFN-a treatment effectiveness

Chihara - epidemiology of ATLL

Ishida/uike - mogalizumab approved in 2012

Phillips - brentuximab