{"entity":{"id":"adult-t-cell-leukaemia-lymphoma","kind":"cancer","name":"Adult T-cell leukaemia/lymphoma","aka":["ATLL","ATL","Adult T-cell leukemia/lymphoma","Adult T-cell leukaemia","HTLV-1-associated lymphoma","Adult T-cell leukaemia/lymphoma (HTLV-1)","Smouldering ATL","Chronic ATL","Acute ATL","Lymphoma-type ATL"],"tldr":"A T-cell lymphoma caused by a virus, HTLV-1, which is usually caught in infancy through breast milk and causes the lymphoma decades later in a small minority of the people it infects. It occurs in people from south-western Japan, the Caribbean, west and central Africa, parts of South America, Iran and Romania, and it comes in four forms that are treated very differently.","summary":"What it is. A cancer of mature CD4-positive T cells caused by human T-lymphotropic virus type 1, the first human retrovirus shown to cause a cancer. The virus is acquired mainly through breastfeeding in infancy, and also through sexual contact and transfusion of cellular blood products. It then sits in the T cells for decades. Only a small minority of the people it infects ever develop the lymphoma, and the latency is usually measured in decades, which is why this is a disease of middle and later life in people who were infected as babies.\n\nThe four forms, which are really four diseases. The subclassification proposed by Shimoyama and adopted by the international consensus meetings divides it into acute, lymphoma, chronic and smouldering types. The chronic and smouldering types without unfavourable features are indolent and are watched, in the same way an early chronic lymphocytic leukaemia is watched. The acute and lymphoma types are aggressive and are treated at once. Getting the type right is the first decision and it changes everything that follows.\n\nHow it differs from the rest of the T-cell family. Four things recur and none of them belongs to ordinary peripheral T-cell lymphoma. High calcium, often very high, caused by the tumour making parathyroid hormone-related protein; it was found in the blood cells of all 13 patients tested in the study that established the mechanism, and it can present as confusion, thirst and kidney failure before the lymphoma is recognised. Profound suppression of cell-mediated immunity, so that opportunistic infection, and particularly hyperinfection with the worm Strongyloides stercoralis, is a common cause of harm and is looked for before treatment. Involvement of the skin, which may be the only sign for a long time and which the 2019 consensus meeting singled out for a classification of its own. And involvement of the central nervous system, which is common in the aggressive types.\n\nWho should be tested. HTLV-1 serology belongs in the work-up of any T-cell lymphoma or leukaemia in a person who comes from, or whose parents come from, an endemic region. Without the test, the disease is reported as peripheral T-cell lymphoma not otherwise specified and treated on a pathway that does not fit it.\n\nWhat is known about treating it, honestly. The 2019 international consensus report states the position of the evidence in its own words: as a result of lower-quality clinical evidence, a best practice approach was adopted and the statements were agreed by more than 90 per cent of the authors. That is a consensus, not a trial result, and it applies to the choice of chemotherapy, to the use of antiviral therapy with zidovudine and interferon in the leukaemic types, and to the place of allogeneic stem cell transplant. The treatment rows on this page were moved here from the peripheral T-cell lymphoma page once this record existed.","asOf":"2026-09-29","wikipedia":"https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"International Consensus Classification of Mature Lymphoid Neoplasms (Campo, Blood 2022)","url":"https://doi.org/10.1182/blood.2022015851"},{"label":"Definition, prognostic factors, treatment and response criteria of adult T-cell leukaemia-lymphoma: a proposal from an international consensus meeting (Tsukasaki, J Clin Oncol 2009)","url":"https://doi.org/10.1200/JCO.2008.18.2428"},{"label":"Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report (Cook, J Clin Oncol 2019)","url":"https://doi.org/10.1200/JCO.18.00501"},{"label":"Increase in incidence of adult T-cell leukaemia/lymphoma in non-endemic areas of Japan and the United States (Chihara, Cancer Science 2012)","url":"https://doi.org/10.1111/j.1349-7006.2012.02373.x"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":["heme","lymphoma","subtype-page"],"related":["peripheral-t-cell-lymphoma","extranodal-nk-t-cell-lymphoma","t-cell-prolymphocytic-leukaemia","non-hodgkin-lymphoma","cutaneous-t-cell-lymphoma"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","allogeneic-hsct"],"targets":[],"drugs":["mogamulizumab","interferon-alfa"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-htlv-1","oncogenic-viruses","lymphoma-classification-2022","lymphoma-pit-score","lymphoma-b-versus-t-cell","lymphoma-tx-transplant-role","lymphoma-tx-regimen-alphabet"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Concentrated where the virus is. In the registry study that compared endemic and non-endemic areas, 2,055 patients were diagnosed in three prefectures of Kyushu in south-western Japan between 1993 and 2006 against 1,380 in twelve prefectures of Honshu, and 140 patients were recorded in the United States SEER registries between 1993 and 2008. Incidence rose significantly in the non-endemic areas over that period (an average annual change of plus 4.6 per cent in Honshu and plus 6.2 per cent in the United States) while remaining unchanged in endemic Kyushu, which the authors read as the virus travelling with its carriers. A systematic review of HTLV-1 among immigrants and refugees worldwide found a pooled prevalence of 1.28 per cent, rising to 7.27 per cent among people from the Western Pacific region.","subtypes":["Acute type, the commonest aggressive form, with circulating tumour cells, high calcium and rapid progression","Lymphoma type, with lymph node disease and few circulating cells, which does not respond to antiviral therapy","Chronic type, indolent unless unfavourable features are present","Smouldering type, indolent, often with skin disease and few circulating cells","Cutaneous variants, which the 2019 consensus meeting singled out for their own classification"],"biomarkers":["HTLV-1 serology, and confirmation that the virus is clonally integrated in the tumour cells","The Shimoyama type (acute, lymphoma, chronic or smouldering), which is the main treatment decision","Serum calcium and lactate dehydrogenase, both part of the subtype definition","A CD4-positive, CD25-positive, CCR4-positive phenotype with loss of CD7","Strongyloides screening before immunosuppressive treatment, because hyperinfection is fatal","Examination of the spinal fluid in the aggressive types, in which involvement of the central nervous system is common"],"standardOfCare":[{"setting":"Testing for the virus, which decides the diagnosis","approach":"HTLV-1 serology belongs in the work-up of any T-cell lymphoma or leukaemia in a person who comes from, or whose parents come from, south-western Japan, the Caribbean, west or central Africa, parts of South America, Iran or Romania. Without the test the disease is reported as peripheral T-cell lymphoma not otherwise specified and treated on a pathway that does not fit it. A positive test is followed by confirmation that the virus is clonally integrated in the tumour cells, because asymptomatic infection is common in those populations and does not by itself mean lymphoma.","refs":["lymphoma-htlv-1","histopathology-ihc","oncogenic-viruses"],"guideline":{"version":"WHO Classification of Haematolymphoid Tumours, 5th edition (2022), with the International Consensus Classification (2022) where they differ","url":"https://doi.org/10.1038/s41375-022-01620-2"}},{"setting":"Working out which of the four types it is","approach":"The subclassification proposed by Shimoyama and adopted by the international consensus meetings divides the disease into acute, lymphoma, chronic and smouldering types, using the count of circulating tumour cells, the lactate dehydrogenase, the calcium and the sites involved. It is the first decision and it changes everything: the chronic and smouldering types without unfavourable features are watched, while the acute and lymphoma types are treated at once. The consensus report sets out prognostic factors and a set of response criteria specific to this disease, which is why trials in it are not reported like trials in other lymphomas.","refs":["lymphoma-htlv-1","lugano-classification","lymphoma-tx-watch-and-wait"],"guideline":{"version":"International consensus meeting report (J Clin Oncol 2009) and its 2019 revision; NCI PDQ","url":"https://doi.org/10.1200/JCO.2008.18.2428"}},{"setting":"What has to be looked for before and during treatment","approach":"Three things that belong to this disease and not to the rest of the family. Calcium, which can be very high because the tumour makes parathyroid hormone-related protein, and which may present as confusion, thirst or kidney failure before the lymphoma is recognised. Strongyloides stercoralis, because the immune suppression caused by the virus allows hyperinfection, which is fatal and is prevented by screening and treating before immunosuppressive therapy. And the central nervous system, which is commonly involved in the aggressive types and is examined by lumbar puncture.","refs":["lymphoma-htlv-1","intrathecal-therapy","lymphoma-tx-pjp-and-infection-prophylaxis"],"guideline":{"version":"Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report (J Clin Oncol 2019)","url":"https://doi.org/10.1200/JCO.18.00501"}},{"setting":"Adult T-cell leukaemia/lymphoma (HTLV-1)","approach":"Caused by human T-lymphotropic virus type 1, acquired in infancy through breastfeeding and causing lymphoma after a latency of decades in a small percentage of those infected. It occurs in people from south-western Japan, the Caribbean, west and central Africa, parts of South America, Romania and Iran, and it is the reason HTLV-1 serology belongs in the work-up of any T-cell lymphoma in a person from those populations.\n\nFour clinical types, and they are treated differently. Smouldering and chronic types without unfavourable features are watched, or treated with zidovudine and interferon alfa, which produces long remissions in the leukaemic types; antiviral therapy does not work in the lymphoma type. Acute and lymphoma types are treated with intensive chemotherapy. JCOG9801 randomised 118 patients with aggressive disease to six courses of VCAP-AMP-VECP or eight courses of biweekly CHOP, both with G-CSF and intrathecal prophylaxis: the complete response rate was 40 against 25 per cent and three-year overall survival 24 against 13 per cent, with more toxicity in the intensive arm (grade 4 neutropenia 98 against 83 per cent, grade 3 or 4 infection 32 against 15 per cent). VCAP-AMP-VECP is standard in Japan; outside Japan, CHOP or CHOEP with early referral for allogeneic transplant is more usual.\n\nAllogeneic stem cell transplant is the only treatment that cures a minority, and it is offered early because remissions are short. Mogamulizumab, an anti-CCR4 antibody first approved in Japan in 2012, produces responses in relapsed aggressive disease: in the updated phase 2 analysis of 26 relapsed patients, median progression-free survival was 5.2 months and median overall survival 14.4 months, and outcomes were better in patients who developed a rash of grade 2 or more, a signal that is being read as an immune effect rather than a side effect alone. Central nervous system involvement is common and intrathecal prophylaxis is given.","refs":["mogamulizumab","interferon-alfa","cyclophosphamide","doxorubicin","vincristine","prednisone","etoposide","carboplatin","allogeneic-hsct","intrathecal-therapy","lymphoma-tx-transplant-role"],"guideline":{"version":"NCCN T-Cell Lymphomas; JCOG9801; Japanese consensus","url":"https://doi.org/10.1200/JCO.2007.11.9958"}}],"stateOfArt":[],"history":[{"year":1977,"title":"Described as a distinct disease in south-western Japan","note":"A cluster of T-cell leukaemias in Kyushu was recognised as a single disease, which led to the search for its cause.","refs":[]},{"year":1990,"title":"The mechanism of the high calcium established","note":"Parathyroid hormone-related protein was found to be abundantly expressed in the blood cells of all 13 patients tested, and in HTLV-1 carriers without symptoms, and the viral Tax protein was shown to switch its gene on.","refs":[]},{"year":2009,"title":"An international consensus defines the four types","note":"The consensus meeting set out the acute, lymphoma, chronic and smouldering types, the prognostic factors and a set of response criteria specific to the disease, which became the standard reference for trials.","refs":[]},{"year":2019,"title":"The consensus revised, on best practice rather than trials","note":"The revised report added the classification of cutaneous disease, disease in the central nervous system, the management of older and transplant-ineligible patients, upfront allogeneic transplant and newer agents, and stated that a best practice approach was adopted because the clinical evidence was of lower quality.","refs":[]}],"pipeline":[],"openProblems":["The treatment of this disease rests on consensus rather than on randomised evidence, and the authors of the consensus say so.","The virus is preventable. Antenatal screening and avoidance of breastfeeding where it is safe to do so reduce transmission, and most of the world does not screen.","The incidence is rising in the places that do not expect it, including the United States and non-endemic Japan, while remaining stable where it is endemic.","Drugs approved for this disease in Japan, including mogamulizumab and later agents, are not approved in much of the world, so the people least likely to be offered them are those who moved away from where the disease is studied."],"parent":"peripheral-t-cell-lymphoma"},"route":"/cancers/adult-t-cell-leukaemia-lymphoma/","neighbours":{"cancer":[{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"id":"extranodal-nk-t-cell-lymphoma","kind":"cancer","name":"Extranodal NK/T-cell lymphoma","route":"/cancers/extranodal-nk-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"t-cell-prolymphocytic-leukaemia","kind":"cancer","name":"T-cell prolymphocytic leukaemia","route":"/cancers/t-cell-prolymphocytic-leukaemia/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"mogamulizumab","kind":"drug","name":"Mogamulizumab","route":"/drugs/mogamulizumab/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"term":[{"id":"lymphoma-b-versus-t-cell","kind":"term","name":"B-cell, T-cell and NK-cell lymphoma","route":"/terms/lymphoma-b-versus-t-cell/"},{"id":"lymphoma-htlv-1","kind":"term","name":"HTLV-1 (human T-lymphotropic virus type 1)","route":"/terms/lymphoma-htlv-1/"},{"id":"lymphoma-tx-pjp-and-infection-prophylaxis","kind":"term","name":"Infection prophylaxis in lymphoma: PJP, herpes, fungal risk and vaccination","route":"/terms/lymphoma-tx-pjp-and-infection-prophylaxis/"},{"id":"intrathecal-therapy","kind":"term","name":"Intrathecal therapy (lumbar puncture, Ommaya reservoir)","route":"/terms/intrathecal-therapy/"},{"id":"lugano-classification","kind":"term","name":"Lugano classification / Ann Arbor staging","route":"/terms/lugano-classification/"},{"id":"lymphoma-pit-score","kind":"term","name":"Prognostic Index for T-cell lymphoma (PIT)","route":"/terms/lymphoma-pit-score/"},{"id":"lymphoma-tx-transplant-role","kind":"term","name":"Stem cell transplant in lymphoma: what it is still for","route":"/terms/lymphoma-tx-transplant-role/"},{"id":"lymphoma-tx-regimen-alphabet","kind":"term","name":"The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest","route":"/terms/lymphoma-tx-regimen-alphabet/"},{"id":"lymphoma-classification-2022","kind":"term","name":"The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)","route":"/terms/lymphoma-classification-2022/"},{"id":"lymphoma-tx-watch-and-wait","kind":"term","name":"Watch and wait in lymphoma: when the right treatment is none yet","route":"/terms/lymphoma-tx-watch-and-wait/"}],"pathway":[{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"}]}}