# Secondary and therapy-related acute myeloid leukaemia

Source: https://onco.cc/cancers/aml-secondary/  
OnCo record `aml-secondary` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Secondary acute myeloid leukaemia grows out of an earlier marrow disorder or follows chemotherapy or radiotherapy for another cancer. It resists standard treatment more than other leukaemias; a liposomal form of the two classic chemotherapy drugs, CPX-351, lengthens life in fit older patients, and transplant is the only route to cure.

## Summary

Two histories lead here. Secondary AML transforms from myelodysplastic syndromes, chronic myelomonocytic leukaemia or a myeloproliferative neoplasm, and carries their spliceosome and chromatin mutations (SRSF2, SF3B1, ASXL1, RUNX1) or a complex karyotype. Therapy-related AML follows alkylating agents and radiotherapy after five to ten years, usually with chromosome 5 and 7 losses and TP53 mutations, or follows topoisomerase II inhibitors within two to three years with KMT2A rearrangements. The WHO and ICC 2022 classifications group most of these as AML with myelodysplasia-related gene mutations or cytogenetics, and the ELN counts them as adverse risk.

CPX-351 packs cytarabine and daunorubicin in a fixed 5:1 molar ratio inside a liposome that concentrates in marrow. Its phase 3 trial (Study 301) randomised 309 patients aged 60 to 75 with newly diagnosed secondary or therapy-related AML against 7+3: median overall survival 9.56 versus 5.95 months (hazard ratio 0.69), and 18 percent versus 8 percent alive at five years, most of the survivors having reached transplant. It was approved in the United States in 2017 and in Europe in 2018 and is the intensive induction of choice for this group. Patients unfit for intensive therapy receive venetoclax with azacitidine, which works less well here than in de novo disease, especially with TP53 mutations.

TP53-mutated disease remains the hardest problem in leukaemia: remissions are short with every regimen, magrolimab and other CD47 antibodies failed in phase 3, and transplant cures only a minority. Avoiding the disease, by choosing regimens for the first cancer that spare the marrow and by watching clonal haematopoiesis in survivors, is as much a research aim as treating it.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Therapy-related AML; t-AML; Secondary AML; AML with myelodysplasia-related changes; AML arising from MDS or MPN
- Tags: subtype-page
- Group: haematologic
- Burden: Roughly a quarter of adult acute myeloid leukaemia arises from a prior marrow disorder or after chemotherapy or radiotherapy for another cancer; it strikes older people and has always done worse than leukaemia arising on its own.
- Subtypes: Secondary AML arising from myelodysplastic syndromes or CMML; Post-MPN blast phase (myelofibrosis, polycythaemia or thrombocythaemia transforming to AML); Therapy-related AML after alkylating agents or radiotherapy (chromosome 5 and 7 loss, TP53); Therapy-related AML after topoisomerase II inhibitors (KMT2A-rearranged); AML with myelodysplasia-related gene mutations
- Biomarkers: TP53 mutation and allelic state; Complex or monosomal karyotype; Myelodysplasia-related mutations (SRSF2, SF3B1, ASXL1, RUNX1, U2AF1, EZH2, BCOR, STAG2); KMT2A rearrangement; Prior clonal haematopoiesis; ELN 2022 risk group

## 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/aml-secondary/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/aml-secondary/#overview [3 state-of-the-art points]
- 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/aml-secondary/#what-it-is [5 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/aml-secondary/#finding-it [6 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/aml-secondary/#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/aml-secondary/#evidence [3 trials, 4 key papers, 4 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/aml-secondary/#science [6 targets, 1 pathway]
- 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/aml-secondary/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/aml-secondary/#living-with-it [17 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/aml-secondary/coming/ [9 medicines, 1 trial, 1 idea, 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/aml-secondary/data/ [51 connected records]

## Standard of care

- Newly diagnosed, fit for intensive chemotherapy, age 60 to 75: CPX-351 induction (Study 301) followed by allogeneic transplant in remission; 7+3 where CPX-351 is unavailable. ([CPX-351 (liposomal daunorubicin-cytarabine)](https://onco.cc/drugs/cpx-351/), [CPX-351 Study 301](https://onco.cc/trials/cpx-351-301/), [Cytarabine + anthracycline ('7+3')](https://onco.cc/drugs/cytarabine-7-3/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- Newly diagnosed, unfit for intensive chemotherapy: Venetoclax plus azacitidine or decitabine; hypomethylating agent alone for TP53-mutated disease where venetoclax adds little; trials. ([Venetoclax](https://onco.cc/drugs/venetoclax/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [Decitabine](https://onco.cc/drugs/decitabine/), [VIALE-A](https://onco.cc/trials/viale-a/))
- Consolidation and relapse: Allogeneic transplant is the only curative option; genotype-directed drugs where a FLT3, IDH or KMT2A target exists. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Revumenib](https://onco.cc/drugs/revumenib/))

## State of the art

- CPX-351 is the standard intensive induction for fit patients with secondary or therapy-related AML, with more patients reaching transplant and surviving five years than with 7+3.
- TP53-mutated AML has no effective standard: every phase 3 that targeted it, including CD47 blockade, has failed.
- Clonal haematopoiesis before chemotherapy is now known to predict which survivors will develop therapy-related leukaemia.

## Open problems

- No regimen produces durable remissions in TP53-mutated AML.
- Whether CPX-351 helps patients under 60 or those fit enough for transplant regardless of induction.
- Predicting and preventing therapy-related leukaemia in cancer survivors with clonal haematopoiesis.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acute_myeloid_leukemia
- Wikipedia: Acute myeloid leukaemia: https://en.wikipedia.org/wiki/Acute_myeloid_leukemia
- NCCN Guidelines: Acute Myeloid Leukemia: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute myeloid leukaemia in children](https://onco.cc/cancers/aml-paediatric/), [Acute myeloid leukaemia in older or unfit patients](https://onco.cc/cancers/aml-older-unfit/), [Acute promyelocytic leukaemia](https://onco.cc/cancers/apl/), [Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)](https://onco.cc/cancers/advanced-systemic-mastocytosis/), [FLT3-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-flt3/), [IDH1- and IDH2-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-idh/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [CD47 and SIRP-alpha blockade](https://onco.cc/technologies/cd47-blockade/)
- targets: [CD47](https://onco.cc/targets/cd47/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/)
- terms: [Alkylating agents and therapy-related myeloid neoplasms](https://onco.cc/terms/rejuv-second-alkylating-agents-and-myeloid-neoplasms/), [AML with myelodysplasia-related gene mutations (AML-MR)](https://onco.cc/terms/aml-myelodysplasia-related/), [ELN 2022 risk classification](https://onco.cc/terms/eln-risk/), [From a clone in the blood to a leukaemia: what is known, and what is done](https://onco.cc/terms/rejuv-second-from-clone-to-disease/), [Hypomethylating agents (azacitidine, decitabine)](https://onco.cc/terms/hma/), [Secondary malignancy (therapy-related cancer)](https://onco.cc/terms/secondary-malignancy/), [SF3B1 mutation](https://onco.cc/terms/sf3b1-mutation/), [Topoisomerase II inhibitors and the shorter latency](https://onco.cc/terms/rejuv-second-topoisomerase-inhibitors-short-latency/), [TP53-mutated (p53-abnormal)](https://onco.cc/terms/tp53-mutated/)
- key papers: [CPX-351 versus 7+3 chemotherapy in older adults with newly diagnosed secondary acute myeloid leukaemia](https://onco.cc/key-papers/paper-cpx-351-study-301-lancet-je-jco-2018/), [ELN 2022: diagnosis and management of acute myeloid leukaemia in adults](https://onco.cc/key-papers/paper-eln-2022-aml-dohner-blood-2022/), [VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy](https://onco.cc/key-papers/paper-viale-a-venetoclax-azacitidine-nejm-2020/), [WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms](https://onco.cc/key-papers/paper-who-2022-myeloid-khoury-leukemia-2022/)
- trials: [CPX-351 Study 301](https://onco.cc/trials/cpx-351-301/), [myeloMATCH](https://onco.cc/trials/myelomatch/), [VIALE-A](https://onco.cc/trials/viale-a/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [CPX-351 (liposomal daunorubicin-cytarabine)](https://onco.cc/drugs/cpx-351/), [Cytarabine + anthracycline ('7+3')](https://onco.cc/drugs/cytarabine-7-3/), [Decitabine](https://onco.cc/drugs/decitabine/), [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Magrolimab](https://onco.cc/drugs/magrolimab/), [Revumenib](https://onco.cc/drugs/revumenib/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- ideas: [Which patients' blood clones will become leukaemia after treatment?](https://onco.cc/ideas/idea-chip-risk-modifiers/)
- people: [Jeffrey E. Lancet](https://onco.cc/people/jeffrey-lancet/)

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JSON: https://onco.cc/api/v1/entities/aml-secondary.json