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Mixed-phenotype acute leukaemia is a rare acute leukaemia whose cells carry markers of both lymphoid and myeloid lines, so it fits neither acute lymphoblastic nor acute myeloid leukaemia. Pooled evidence favours starting with the drugs used for acute lymphoblastic leukaemia, adding a targeted drug when the Philadelphia chromosome is present, and a stem cell transplant in first remission.
WHO-HAEM5 keeps mixed-phenotype acute leukaemia under acute leukaemias of ambiguous lineage, defined by blasts co-expressing lineage-defining markers (B or T with myeloid) or by two blast populations, and subdivided by genetics, BCR::ABL1 and KMT2A-rearranged, then by phenotype (B/myeloid, T/myeloid, rare types) (Khoury 2022). The meta-analysis of 1,351 evaluable patients found that acute myeloid leukaemia-type induction was less likely to achieve complete remission than acute lymphoblastic leukaemia-type or hybrid induction, and analysed survival by treatment type and transplant (Maruffi 2018). In the Children's Oncology Group cohort, acute lymphoblastic leukaemia regimens achieved remission in 72 percent (28 of 39) and acute myeloid leukaemia regimens in 69 percent (9 of 13), and the task force set out a prospective trial strategy for paediatric disease (Orgel 2020).
How it differs from its parent: it sits between the two acute leukaemia pages; its diagnosis depends on strict flow cytometry criteria (myeloperoxidase or monocytic markers for myeloid lineage, cytoplasmic CD3 for T, CD19 with CD79a, CD22 or CD10 for B), and its treatment has no randomised evidence, only pooled case series.
How common: usually quoted as 2 to 5 percent of acute leukaemias, but no registry figure is in the sources read.
Treatment: acute lymphoblastic leukaemia-type induction in most patients, with a tyrosine kinase inhibitor added for BCR::ABL1 disease and menin inhibitors under study for KMT2A-rearranged disease; allogeneic transplant in first remission for adults and high-risk children; measurable residual disease guides the choice, following the acute lymphoblastic and acute myeloid leukaemia pages (Maruffi 2018; Orgel 2020).
Rare: a systematic review compiled 1,499 unique patients from 97 reports in 33 countries (Maruffi 2018); the Children's Oncology Group confirmed 54 of 70 banked cases as meeting WHO 2016 criteria (Orgel 2020). Usually quoted as 2 to 5 percent of acute leukaemias; no registry figure is in the sources read.
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: 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, 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
Acute lymphoblastic leukaemia-type induction in most patients; tyrosine kinase inhibitor for BCR::ABL1 disease; allogeneic transplant in first remission for adults and high-risk children.
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Query for this cancer: (TITLE:"Mixed-phenotype acute leukaemia" OR ABSTRACT:"Mixed-phenotype acute leukaemia" OR TITLE:"MPAL" OR ABSTRACT:"MPAL" OR TITLE:"Mixed phenotype acute leukemia" OR ABSTRACT:"Mixed phenotype acute leukemia" OR TITLE:"Acute biphenotypic leukaemia" OR ABSTRACT:"Acute biphenotypic leukaemia" OR TITLE:"Acute biphenotypic leukemia" OR ABSTRACT:"Acute biphenotypic leukemia" OR TITLE:"Bilineal acute leukaemia" OR ABSTRACT:"Bilineal acute leukaemia") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Mixed-phenotype acute leukaemia, not a curated reading list.
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Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Take with a meal and a large glass of water.
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
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