Secondary and therapy-related acute myeloid leukaemia
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.
Overview
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.
State of the art
- TP53-mutated AML has no effective standard: every phase 3 that targeted it, including CD47 blockade, has failed.
Show survival figures (2)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
- Clonal haematopoiesis before chemotherapy is now known to predict which survivors will develop therapy-related leukaemia.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowDifferentiation syndrome
Fever, cough or breathlessness, rapid weight gain or swelling, bone pain, low blood pressure or reduced urine; the labels say to start steroids and monitor at the first suspicion, and the syndrome has been fatal.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowTumour lysis syndrome
Nausea, vomiting, muscle cramps, palpitations, seizures, confusion or passing much less urine in the first days of a new dose; the label requires hydration, anti-hyperuricaemic drugs and blood tests around each ramp-up step.
- Check before combiningGilteritinib with Ivosidenib: major interaction
QT: both Gilteritinib and Ivosidenib prolong the QT interval (known and known risk).. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Check before combiningGilteritinib with Revumenib: major interaction
QT: both Gilteritinib and Revumenib prolong the QT interval (known and known risk).. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
See all on the product pages:AzacitidineCPX-351 (liposomal daunorubicin-cytarabine)Cytarabine + anthracycline ('7+3')DecitabineGilteritinibIvosidenibRevumenibVenetoclax·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
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.
- Bone marrow (leukaemia, MDS, MPN, myeloma)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
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
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: 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, 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
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.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
CPX-351 induction (Study 301) followed by allogeneic transplant in remission; 7+3 where CPX-351 is unavailable.
Venetoclax plus azacitidine or decitabine; hypomethylating agent alone for TP53-mutated disease where venetoclax adds little; trials.
Allogeneic transplant is the only curative option; genotype-directed drugs where a FLT3, IDH or KMT2A target exists.
Subtypes & biomarkers
top- 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
- 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
How often this target appears
- 1970Therapy-related leukaemia recognised after alkylating agents for Hodgkin lymphoma
- 2016WHO defines AML with myelodysplasia-related changes as its own group
- 2017CPX-351 approved after Study 301 lengthens life in secondary AML
- 2023Magrolimab with azacitidine fails in TP53-mutated AML
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 9 changes by month →- 2026-09-17This recordSecondary and therapy-related acute myeloid leukaemiaFacts on this page last checked
When this page itself was last checked or edited.
- 2023MilestoneMagrolimabMagrolimab with azacitidine fails in TP53-mutated AML
A milestone in how this cancer is treated.
- 2020Trial resultVIALE-AVIALE-A reported
OS 14.
- 2018Trial resultCPX-351 Study 301CPX-351 Study 301 reported
OS 9.
- 2017ApprovalCPX-351 (liposomal daunorubicin-cytarabine)CPX-351 (liposomal daunorubicin-cytarabine) approved in US
Newly diagnosed therapy-related AML or AML with myelodysplasia-related changes, adults
- 2017MilestoneCPX-351 Study 301CPX-351 approved after Study 301 lengthens life in secondary AML
A milestone in how this cancer is treated.
What is in development for Secondary and therapy-related acute myeloid leukaemia, drawn from the whole corpus: 4 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Technologies being tested · 1
Trials under way · 1
- myeloMATCH · phase platform · NCI / National Clinical Trials Network
Trials reported · 1
- CPX-351 Study 301 · phase 3 · 2018 · positive
Ideas not yet in a trial · 1
Open problems and what is being done
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.
Trials
topTrials recruiting now
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.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Boston · cancer center | United States | 0 | 4,335 | 73,845 | none recorded | #15 | |
Bethesda, MD · government | United States | none recorded | 1 | 2,905 | 47,715 | - | |
Los Angeles, CA · cancer center | United States | 0 | 318 | 3,917 | - | ||
Melbourne · research institute | Australia | none recorded | 0 | 298 | 3,639 | - | |
Indianapolis, IN · cancer center | United States | 0 | 159 | 4,238 | - | ||
Hamilton, ON · cancer center | Canada | none recorded | 0 | 103 | 1,158 | - | |
Baltimore, MD · cancer center | United States | 0 | 101 | 2,306 | - | ||
Omaha, NE · cancer center | United States | 0 | 37 | 4,159 | - | ||
Rotterdam · consortium | Netherlands | none recorded | 0 | 8 | 207 | - | |
Minneapolis, MN · cancer center | United States | 0 | not matched | - | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Secondary and therapy-related acute myeloid leukaemia but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Secondary and therapy-related acute myeloid leukaemia
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example TP53 mutation and allelic state, Complex or monosomal karyotype, Myelodysplasia-related mutations, KMT2A rearrangement, Prior clonal haematopoiesis), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Secondary AML arising from myelodysplastic syndromes or CMML, Post-MPN blast phase, Therapy-related AML after alkylating agents or radiotherapy.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Newly diagnosed, fit for intensive chemotherapy, age 60 to 75
- For my situation (newly diagnosed, fit for intensive chemotherapy, age 60 to 75), which of the standard options do you recommend and why?Why: Guideline options include: CPX-351 induction (Study 301) followed by allogeneic transplant in remission; 7+3 where CPX-351 is unavailable.
- Am I a candidate for CPX-351 (liposomal daunorubicin-cytarabine), Cytarabine + anthracycline ('7+3'), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CPX-351 Study 301 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Newly diagnosed, unfit for intensive chemotherapy
- For my situation (newly diagnosed, unfit for intensive chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Venetoclax plus azacitidine or decitabine; hypomethylating agent alone for TP53-mutated disease where venetoclax adds little; trials.
- Am I a candidate for Venetoclax, Azacitidine, Decitabine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of VIALE-A apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Consolidation and relapse
- For my situation (consolidation and relapse), which of the standard options do you recommend and why?Why: Guideline options include: Allogeneic transplant is the only curative option; genotype-directed drugs where a FLT3, IDH or KMT2A target exists.
- Am I a candidate for Gilteritinib, Ivosidenib, Revumenib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of CPX-351 (liposomal daunorubicin-cytarabine), Venetoclax, myeloMATCH, Which patients' blood clones will become leukaemia after treatment??Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No regimen produces durable remissions in TP53-mutated AML”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether CPX-351 helps patients under 60 or those fit enough for transplant regardless of induction”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Secondary and therapy-related acute myeloid leukaemia, 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.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
8targets
6drugs
9companies
9pathways
1terms
4trials
3ideas
1Latest papers
topQuery for this cancer: (TITLE:"Secondary and therapy-related acute myeloid leukaemia" OR ABSTRACT:"Secondary and therapy-related acute myeloid leukaemia" OR TITLE:"Therapy-related AML" OR ABSTRACT:"Therapy-related AML" OR TITLE:"t-AML" OR ABSTRACT:"t-AML" OR TITLE:"Secondary AML" OR ABSTRACT:"Secondary AML" OR TITLE:"AML with myelodysplasia-related changes" OR ABSTRACT:"AML with myelodysplasia-related changes" OR TITLE:"AML arising from MDS or MPN" OR ABSTRACT:"AML arising from MDS or MPN") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Secondary and therapy-related acute myeloid leukaemia, not a curated reading list.
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