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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.
Higher-risk myelodysplastic syndromes behave like a slow leukaemia and often become one. Azacitidine lengthens life and a donor stem cell transplant is the only cure; every attempt to improve on azacitidine in a large trial, including the venetoclax combination tested in VERONA, has so far failed.
Higher-risk disease is IPSS-R above 3.5 (intermediate with adverse features, high and very high) or IPSS-M moderate-high and above: excess blasts (5 to 19 percent), adverse cytogenetics including complex karyotype and chromosome 7 loss, deep cytopenias and mutations such as TP53, ASXL1, RUNX1 and EZH2. Multi-hit TP53 disease is the worst group and is now classified separately by both WHO and ICC. The goal shifts from managing cytopenias to changing the natural history, and the first question at diagnosis is whether the patient can reach an allogeneic transplant.
Azacitidine is the standard for those who cannot: AZA-001 (2009) showed median survival of 24.5 months against 15 months with conventional care, the first drug to lengthen life in MDS, and decitabine and the oral decitabine-cedazuridine combination (2020) are equivalents. For fit patients up to about 75, allogeneic transplant is the only cure; the BMT CTN 1102 donor-versus-no-donor study (2021) found three-year survival of 47.9 percent with a donor against 26.6 percent without, and most centres give hypomethylating therapy to bridge and debulk before transplant. Relapse after transplant remains common in TP53-mutated disease.
| Setting | Approach | Guideline |
|---|---|---|
| Transplant candidate | Allogeneic stem cell transplant after donor search, usually with azacitidine or decitabine to bridge and reduce blasts; reduced-intensity conditioning in older patients. | not mapped |
| Not a transplant candidate | Azacitidine (AZA-001) or decitabine, or oral decitabine-cedazuridine, continued until progression; trials of hypomethylating agent combinations. | not mapped |
| Failure of hypomethylating therapy | Clinical trial; venetoclax combinations off-label in selected patients; genotype-directed drugs where IDH, FLT3 or KMT2A targets exist; best supportive care. | not mapped |