Loading
An aggressive T-cell lymphoma that looks like its ALK-positive sibling under the microscope and carries the same CD30 marker, but lacks the broken ALK gene. It affects older people and is cured less often, and several genetic changes inside it predict very different outcomes.
What it is. A lymphoma of T cells that looks anaplastic, carries uniform strong CD30 and has no ALK rearrangement. The definition is therefore partly negative, which is why WHO-HAEM5 describes it as a heterogeneous entity: it is what is left when ALK-positive disease, breast implant-associated disease and the skin lymphomas have been excluded.
How it differs from its ALK-positive sibling. In age, and in outcome. ALK-positive disease affects people in their twenties and thirties; this affects people around 70. Both carry CD30, both are treated with the same first-line regimen, and ALK-positive disease is cured considerably more often. Where the appearance is identical, only the ALK stain tells them apart, which is why it is done on every anaplastic lymphoma.
What is inside it, and what that is worth. Sequencing has found several genetic contexts within ALK-negative disease, and WHO-HAEM5 is careful about how much weight to put on them: it says there are not currently enough data to decide whether they are prognostic markers or genuine molecular subtypes. Rearrangement of TP63, loss of TP53 and overexpression of the interleukin-2 receptor alpha chain are each associated with worse outcomes. DUSP22 rearrangement was initially reported to carry a five-year survival as good as ALK-positive disease, and WHO-HAEM5 notes that more recent studies have not confirmed that association, which is the sort of reversal worth knowing about before a prognosis is given on the strength of it.
Some of the genetics show in the appearance. Tumours with a DUSP22 rearrangement have cells with a doughnut-like shape and grow in sheets with less variation in size, and LEF1 staining may be a surrogate for the rearrangement. A group with a Hodgkin-like appearance shows aberrant ERBB4 protein, and the cells look more anaplastic where JAK2 is rearranged.
How it is treated. The same as the other CD30-positive nodal T-cell lymphomas: brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone, on the strength of ECHELON-2, and consolidation of a first remission with an autologous stem cell transplant in people fit for it, which is convention rather than demonstrated benefit. The detail is on the peripheral T-cell lymphoma page and in the treatment layer of this family.
In the United Kingdom population series that reports lymphoma by subtype, 27 of 5,796 lymphomas were ALK-negative anaplastic large cell lymphoma, a European age-standardised rate of 0.08 per 100,000 a year, with a median age at diagnosis of 69.0 years, more than thirty years older than the ALK-positive form.
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-positive 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
CD30 and ALK immunohistochemistry on the biopsy. The diagnosis is partly a negative one: uniform strong CD30 with an anaplastic appearance and no ALK, in a lymphoma that is not confined to the skin and is not associated with a breast implant. Those two exclusions matter because both of them are treated very differently. Testing for DUSP22 and TP63 rearrangements is done where it is available, with the caution that WHO-HAEM5 does not regard the resulting groups as established subtypes.
Brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone, the same regimen as for ALK-positive disease and on the same trial: in ECHELON-2, five-year progression-free survival was 51.4 per cent against 43.0 with chemotherapy alone and overall survival 70.1 against 61.0. Consolidating a first remission with high-dose therapy and an autologous stem cell transplant is standard practice here, unlike in ALK-positive disease, and it rests on a single-arm study and registry comparisons rather than on a randomised trial; a patient is entitled to be told that. The regimens are on the peripheral T-cell lymphoma page.
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Query for this cancer: (TITLE:"ALK-negative anaplastic large cell lymphoma" OR ABSTRACT:"ALK-negative anaplastic large cell lymphoma" OR TITLE:"ALK-negative ALCL" OR ABSTRACT:"ALK-negative ALCL" OR TITLE:"ALK- ALCL" OR ABSTRACT:"ALK- ALCL" OR TITLE:"Anaplastic large cell lymphoma, ALK-negative" OR ABSTRACT:"Anaplastic large cell lymphoma, ALK-negative" OR TITLE:"ALK-negative ALCL DUSP22, TP63 subsets" OR ABSTRACT:"ALK-negative ALCL DUSP22, TP63 subsets" OR TITLE:"Systemic ALK-negative anaplastic large cell lymphoma" OR ABSTRACT:"Systemic ALK-negative anaplastic large cell lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about ALK-negative anaplastic large cell lymphoma, not a curated reading list.
The fourth edition of the WHO classification made ALK-negative anaplastic large cell lymphoma a distinct entity rather than a variant, on the strength of its different biology and clinical course.
Rearrangements of DUSP22 and TP63 were identified within ALK-negative disease and reported to carry very different outcomes, which raised the question of whether the entity should be split again.
WHO-HAEM5 states that there are not yet enough data to decide whether the genetic contexts are prognostic markers or molecular subtypes, and that the favourable outcome first reported for DUSP22 rearrangement has not been confirmed by more recent studies.
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
Newly diagnosed? Read the first 60 days with ALK-negative anaplastic large cell lymphoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
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.