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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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. | not mapped |
| Newly diagnosed, unfit for intensive chemotherapy | Venetoclax plus azacitidine or decitabine; hypomethylating agent alone for TP53-mutated disease where venetoclax adds little; trials. | not mapped |
| Consolidation and relapse | Allogeneic transplant is the only curative option; genotype-directed drugs where a FLT3, IDH or KMT2A target exists. | not mapped |