{"entity":{"id":"alk-positive-anaplastic-large-cell-lymphoma","kind":"cancer","name":"ALK-positive anaplastic large cell lymphoma","aka":["ALK-positive ALCL","ALK+ ALCL","Anaplastic large cell lymphoma, ALK-positive","ALK-positive anaplastic large-cell lymphoma","Systemic ALK-positive anaplastic large cell lymphoma"],"tldr":"An aggressive T-cell lymphoma, mostly of children and young adults, whose cells carry a broken ALK gene and a protein called CD30 on the surface. Despite looking alarming down the microscope it is the T-cell lymphoma most often cured, and both of its markers are things that drugs can aim at.","summary":"What it is. A lymphoma of T cells in which a piece of chromosome 2 carrying the ALK gene has joined another gene, most often NPM1 on chromosome 5, producing a fusion protein that is permanently switched on and drives the cell to divide. Every cell also carries CD30, strongly and uniformly, which is the second thing that makes this disease unusual.\n\nHow it differs from the rest of the family. WHO-HAEM5 recognises three anaplastic large cell lymphomas: this one, the ALK-negative form and the breast implant-associated form, with the primary cutaneous form filed among the skin lymphomas. ALK-positive disease has been separated from ALK-negative disease since the fourth edition because its cause and its course are different, and the difference is large: it occurs in much younger people and is cured far more often.\n\nHow it presents. Often dramatically, with fevers, weight loss, enlarged lymph nodes and disease outside the lymph nodes, in skin, bone, soft tissue, lung or liver. The cells are large and strange-looking, including the hallmark cells with kidney-shaped nuclei, and a pathologist who does not stain for CD30 and ALK can mistake the disease for a carcinoma or a sarcoma. That is a real and recorded error, and it is the reason the two stains are done.\n\nWhy CD30 matters more here than anywhere else. Brentuximab vedotin is an antibody against CD30 carrying a chemotherapy drug. ECHELON-2 randomised 452 people with untreated CD30-positive peripheral T-cell lymphoma, with the trial deliberately targeting 75 per cent with systemic anaplastic large cell lymphoma, to brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone or to the same chemotherapy with vincristine instead of the antibody. At five years, progression-free survival was 51.4 against 43.0 per cent and overall survival 70.1 against 61.0 per cent. It is the only randomised first-line trial in the whole T-cell family to improve survival, and most of its patients had this disease or its ALK-negative sibling.\n\nWhat ALK offers that nothing else in this family does. ALK inhibitors, developed for lung cancer, work here too; crizotinib has activity in relapsed ALK-positive disease and is used particularly in children. That is unusual in T-cell lymphoma, where targeted drugs have mostly disappointed, and it exists only because the same gene was broken in a much commoner cancer.","asOf":"2026-09-29","wikipedia":"https://en.wikipedia.org/wiki/Anaplastic_large-cell_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":"ECHELON-2: brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma, five-year results (Horwitz, Annals of Oncology 2022)","url":"https://doi.org/10.1016/j.annonc.2021.12.002"},{"label":"Lymphoma incidence, survival and prevalence 2004 to 2014, subtype analyses from the UK Haematological Malignancy Research Network (Smith, Br J Cancer 2015)","url":"https://doi.org/10.1038/bjc.2015.94"},{"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":["alk-negative-anaplastic-large-cell-lymphoma","primary-cutaneous-anaplastic-large-cell-lymphoma","breast-implant-associated-alcl","peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","fdg-pet","adc"],"targets":["alk","cd30"],"drugs":["brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-classification-2022","lymphoma-b-versus-t-cell","lymphoma-pit-score","ipi-score","lymphoma-tx-regimen-alphabet","lymphoma-tx-transplant-role"],"trials":["echelon-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Rare and young. In the United Kingdom population series that reports lymphoma by subtype, 16 of 5,796 lymphomas were ALK-positive anaplastic large cell lymphoma, a European age-standardised rate of 0.06 per 100,000 a year, with men affected about three times as often as women and a median age at diagnosis of 35.6 years, the youngest of any lymphoma in that series apart from Hodgkin lymphoma and Burkitt lymphoma. Five-year relative survival in that series was 75.2 per cent.","subtypes":["Common pattern, the great majority","Lymphohistiocytic, small cell and Hodgkin-like patterns, which look different and behave the same"],"biomarkers":["ALK rearrangement, most often NPM1::ALK from t(2;5)(p23;q35), detected by immunohistochemistry for the ALK protein and confirmed by fluorescence in situ hybridisation","Uniform strong CD30 on every tumour cell, which is what brentuximab vedotin attaches to","Loss of several T-cell markers, which is characteristic and can make the lineage hard to establish","Epithelial membrane antigen, often positive, which contributes to the mistaken diagnosis of carcinoma","The International Prognostic Index, which separates outcomes here as it does in B-cell lymphoma"],"standardOfCare":[{"setting":"Making the diagnosis, and the mistake to avoid","approach":"Immunohistochemistry for CD30 and for ALK protein on the biopsy, with fluorescence in situ hybridisation to confirm the rearrangement where the stain is equivocal. The large pleomorphic cells, the frequent expression of epithelial membrane antigen and the loss of several T-cell markers mean that a tumour stained with a short panel can be reported as a carcinoma or a sarcoma; CD30 and ALK are what prevent that. Staging covers the sites this disease reaches outside the lymph nodes: skin, bone, soft tissue, lung and liver.","refs":["histopathology-ihc","cd30","alk","fdg-pet","lugano-classification"],"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":"First-line treatment","approach":"Brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone, on the strength of ECHELON-2, which randomised 452 people with untreated CD30-positive peripheral T-cell lymphoma, three-quarters of them with systemic anaplastic large cell lymphoma: five-year progression-free survival 51.4 per cent against 43.0 and overall survival 70.1 against 61.0 with chemotherapy alone. Vincristine is left out because brentuximab vedotin is itself a tubulin-directed agent and giving both causes unacceptable nerve damage. Unlike the other nodal T-cell lymphomas, ALK-positive disease does well enough that consolidating a first remission with an autologous transplant is generally not offered. The regimens and the cycle detail are on the peripheral T-cell lymphoma page.","refs":["echelon-2","brentuximab-vedotin","cyclophosphamide","doxorubicin","prednisone","peripheral-t-cell-lymphoma","lymphoma-tx-regimen-alphabet"],"guideline":{"version":"ECHELON-2 five-year results (Annals of Oncology 2022); NCCN T-Cell Lymphomas; NCI PDQ","url":"https://doi.org/10.1016/j.annonc.2021.12.002"}},{"setting":"Relapse","approach":"Brentuximab vedotin is highly active in relapsed systemic anaplastic large cell lymphoma, with response rates well above those seen in other peripheral T-cell lymphomas, and it is the usual choice for anyone who has not already had it. ALK inhibitors developed for lung cancer, crizotinib in particular, produce responses here and are used especially in children and young adults. Allogeneic transplant is offered to fit patients who respond. The detail is on the peripheral T-cell lymphoma page.","refs":["brentuximab-vedotin","peripheral-t-cell-lymphoma","allogeneic-hsct","lymphoma-tx-transplant-role","alk"],"guideline":{"version":"NCI PDQ: adult non-Hodgkin lymphoma treatment","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}}],"stateOfArt":[],"history":[{"year":1994,"title":"The ALK fusion identified","note":"NPM1::ALK was found in anaplastic large cell lymphoma, which split the disease into two and made the ALK-positive form the one with the better outlook.","refs":["alk"]},{"year":2011,"title":"Brentuximab vedotin approved for relapsed disease","note":"The CD30 antibody-drug conjugate was approved for systemic anaplastic large cell lymphoma after failure of previous treatment, on high response rates in a small single-arm trial.","refs":["brentuximab-vedotin"]},{"year":2022,"title":"Five-year results of ECHELON-2","note":"In 452 patients with CD30-positive peripheral T-cell lymphoma, three-quarters of them with systemic anaplastic large cell lymphoma, five-year progression-free survival was 51.4 per cent with brentuximab vedotin and chemotherapy against 43.0 per cent with chemotherapy alone, and overall survival 70.1 against 61.0 per cent.","refs":["echelon-2","brentuximab-vedotin"]}],"pipeline":[],"openProblems":["ECHELON-2 enrolled CD30-positive peripheral T-cell lymphoma and was weighted towards anaplastic large cell lymphoma, so the benefit in the other CD30-positive entities is extrapolated rather than demonstrated.","Whether an ALK inhibitor should be added to first-line treatment, or substituted for part of it, has not been tested in a randomised trial.","Most of the ALK-positive patients are young, and the late effects of anthracycline chemotherapy in a cured 30-year-old are measured in decades and are not recorded in the trials."],"parent":"peripheral-t-cell-lymphoma"},"route":"/cancers/alk-positive-anaplastic-large-cell-lymphoma/","neighbours":{"cancer":[{"id":"alk-negative-anaplastic-large-cell-lymphoma","kind":"cancer","name":"ALK-negative anaplastic large cell lymphoma","route":"/cancers/alk-negative-anaplastic-large-cell-lymphoma/"},{"id":"breast-implant-associated-alcl","kind":"cancer","name":"Breast implant-associated anaplastic large cell lymphoma","route":"/cancers/breast-implant-associated-alcl/"},{"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":"primary-cutaneous-anaplastic-large-cell-lymphoma","kind":"cancer","name":"Primary cutaneous anaplastic large cell lymphoma","route":"/cancers/primary-cutaneous-anaplastic-large-cell-lymphoma/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"}],"drug":[{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"}],"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":"ipi-score","kind":"term","name":"International Prognostic Index (IPI)","route":"/terms/ipi-score/"},{"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/"}],"trial":[{"id":"echelon-2","kind":"trial","name":"ECHELON-2","route":"/trials/echelon-2/"}]}}