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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.
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.
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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
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.
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.
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.
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Query for this cancer: (TITLE:"ALK-positive anaplastic large cell lymphoma" OR ABSTRACT:"ALK-positive anaplastic large cell lymphoma" OR TITLE:"ALK-positive ALCL" OR ABSTRACT:"ALK-positive ALCL" OR TITLE:"ALK+ ALCL" OR ABSTRACT:"ALK+ ALCL" OR TITLE:"Anaplastic large cell lymphoma, ALK-positive" OR ABSTRACT:"Anaplastic large cell lymphoma, ALK-positive" OR TITLE:"ALK-positive anaplastic large-cell lymphoma" OR ABSTRACT:"ALK-positive anaplastic large-cell lymphoma" OR TITLE:"Systemic ALK-positive anaplastic large cell lymphoma" OR ABSTRACT:"Systemic ALK-positive anaplastic large cell lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about ALK-positive anaplastic large cell lymphoma, not a curated reading list.
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.
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.
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.
The targets of this cancer's medicines and the ones linked to it directly.
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.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Any new neurological symptom that is not explained. Brentuximab vedotin carries a boxed warning for progressive multifocal leukoencephalopathy, a brain infection; the label says to hold the drug and investigate at the first suspicion.
Temperature of 38 C or higher, or feeling shivery and unwell even without a fever. Antibody-drug conjugates suppress the bone marrow, and several carry a boxed warning for severe neutropenia.
Tingling, numbness or weakness that affects walking or using the hands; peripheral neuropathy is common with the vedotin (MMAE) payload and doses are reduced or stopped at grade 2 to 3.
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
Reduce by 50% for bilirubin 20-50 µmol/L and 75% for 50-85 µmol/L.
See all on the product pages:Brentuximab vedotinCyclophosphamideDoxorubicin·Printable cards in the navigator
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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.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.