# ALK-positive anaplastic large cell lymphoma

Source: https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/  
OnCo record `alk-positive-anaplastic-large-cell-lymphoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

How 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.

How 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.

Why 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.

What 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-29
- Also known as: ALK-positive ALCL; ALK+ ALCL; Anaplastic large cell lymphoma, ALK-positive; ALK-positive anaplastic large-cell lymphoma; Systemic ALK-positive anaplastic large cell lymphoma
- Tags: heme; lymphoma; subtype-page
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/alk-positive-anaplastic-large-cell-lymphoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#overview
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#what-it-is [2 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#treating-it [3 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#evidence [1 trial, 3 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#science [2 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/#living-with-it [14 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/coming/ [4 medicines, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/alk-positive-anaplastic-large-cell-lymphoma/data/ [23 connected records]

## Standard of care

- Making the diagnosis, and the mistake to avoid: 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. ([Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [CD30](https://onco.cc/targets/cd30/), [ALK](https://onco.cc/targets/alk/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/))
- First-line treatment: 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. ([ECHELON-2](https://onco.cc/trials/echelon-2/), [Brentuximab vedotin](https://onco.cc/drugs/brentuximab-vedotin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Prednisone](https://onco.cc/drugs/prednisone/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/))
- Relapse: 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. ([Brentuximab vedotin](https://onco.cc/drugs/brentuximab-vedotin/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Stem cell transplant in lymphoma: what it is still for](https://onco.cc/terms/lymphoma-tx-transplant-role/), [ALK](https://onco.cc/targets/alk/))

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Anaplastic_large-cell_lymphoma
- WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022): https://doi.org/10.1038/s41375-022-01620-2
- International Consensus Classification of Mature Lymphoid Neoplasms (Campo, Blood 2022): https://doi.org/10.1182/blood.2022015851
- ECHELON-2: brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma, five-year results (Horwitz, Annals of Oncology 2022): https://doi.org/10.1016/j.annonc.2021.12.002
- Lymphoma incidence, survival and prevalence 2004 to 2014, subtype analyses from the UK Haematological Malignancy Research Network (Smith, Br J Cancer 2015): https://doi.org/10.1038/bjc.2015.94
- NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version): https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq

## Connected records

- cancers: [ALK-negative anaplastic large cell lymphoma](https://onco.cc/cancers/alk-negative-anaplastic-large-cell-lymphoma/), [Breast implant-associated anaplastic large cell lymphoma](https://onco.cc/cancers/breast-implant-associated-alcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Primary cutaneous anaplastic large cell lymphoma](https://onco.cc/cancers/primary-cutaneous-anaplastic-large-cell-lymphoma/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [ALK](https://onco.cc/targets/alk/), [CD30](https://onco.cc/targets/cd30/)
- drugs: [Brentuximab vedotin](https://onco.cc/drugs/brentuximab-vedotin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Prednisone](https://onco.cc/drugs/prednisone/)
- terms: [B-cell, T-cell and NK-cell lymphoma](https://onco.cc/terms/lymphoma-b-versus-t-cell/), [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [Prognostic Index for T-cell lymphoma (PIT)](https://onco.cc/terms/lymphoma-pit-score/), [Stem cell transplant in lymphoma: what it is still for](https://onco.cc/terms/lymphoma-tx-transplant-role/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/), [The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)](https://onco.cc/terms/lymphoma-classification-2022/)
- trials: [ECHELON-2](https://onco.cc/trials/echelon-2/)

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JSON: https://onco.cc/api/v1/entities/alk-positive-anaplastic-large-cell-lymphoma.json