HOME

TheInfoList



OR:

Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's
T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s caused by human T cell leukemia/lymphotropic virus type 1 (
HTLV-1 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseas ...
). 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. 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. 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).


Signs and symptoms

ATL is usually a highly aggressive
non-Hodgkin's lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness ...
with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prope ...
. Circulating
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
s with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that
HTLV-1 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseas ...
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 the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding gen ...
in ATL leukemic cells. ATL is frequently accompanied by visceral involvement,
hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia ...
,
skin lesion A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...
s, and lytic bone lesions. Bone invasion and
osteolysis Osteolysis is an active resorption of bone matrix by osteoclasts and can be interpreted as the reverse of ossification. Although osteoclasts are active during the natural formation of healthy bone the term "osteolysis" specifically refers to a path ...
, 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 Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anem ...
are predisposed to the development of tumor-induced osteolysis and hypercalcemia. One of the striking features of ATL and
multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anem ...
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 A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...
, probably occurs for life and can be inferred when
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against HTLV-1 is detected in the serum.


Transmission

Transmission of
HTLV-1 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseas ...
is believed to occur from mother to child; by sexual contact; and through exposure to contaminated blood, either through
blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
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 Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child ...
and the CHOP regimen.
Pralatrexate Pralatrexate, sold under the brand name Folotyn, is a medication used for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Pralatrexate was approved for medical use in the United States in September 2009, as the first ...
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 Mogamulizumab, sold under the brand name Poteligeo, is a humanized, afucosylated monoclonal antibody targeting CC chemokine receptor 4 (CCR4). The U.S. Food and Drug Administration (FDA) approved it in August 2018 for treatment of relapsed or ...
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 Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. ...
in CD 30+ cases may be beneficial and supported by current NCCN guidelines.


Epidemiology

HTLV-1 infection in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territo ...
appears to be rare. Although little
serologic Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
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 New Jersey is a state in the Mid-Atlantic and Northeastern regions of the United States. It is bordered on the north and east by the state of New York; on the east, southeast, and south by the Atlantic Ocean; on the west by the Delaware ...
, and a rate of 49% has been found in a similar group in
New Orleans New Orleans ( , ,New Orleans
Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
, in the
Caribbean The Caribbean (, ) ( es, El Caribe; french: la Caraïbe; ht, Karayib; nl, De Caraïben) is a region of the Americas that consists of the Caribbean Sea, its islands (some surrounded by the Caribbean Sea and some bordering both the Caribbean S ...
, South America, and in
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
. ATL is relatively uncommon among those infected with
HTLV-1 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseas ...
. The overall incidence of ATL is estimated at 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 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseas ...
infection and the start of ATL.


Research

Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.
Pralatrexate Pralatrexate, sold under the brand name Folotyn, is a medication used for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Pralatrexate was approved for medical use in the United States in September 2009, as the first ...
is one compound currently under investigations for the treatment of PTCL.


References


Further reading

* * * Genoveffa Franchini's NCI page
Human Retroviral Diseases: Pathogenesis and Prevention

International Retrovirology Association


External links

{{DEFAULTSORT:Adult T-Cell Leukemia Lymphoma Acute lymphocytic leukemia Animal viral diseases Rare cancers Sexually transmitted diseases and infections Lymphoma