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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.
Acute promyelocytic leukaemia is caused by a single fused gene that freezes blood cells at an immature stage and triggers dangerous bleeding. Two non-chemotherapy drugs, a vitamin A derivative and arsenic trioxide, make the cells mature and cure more than nine in ten patients.
The t(15;17) translocation fuses PML to the retinoic acid receptor alpha gene. The PML::RARA protein blocks differentiation at the promyelocyte stage, and the promyelocytes release procoagulants that cause a bleeding and clotting disorder responsible for most early deaths. Diagnosis is a clinical emergency: all-trans retinoic acid (ATRA) is started on suspicion, before the fusion is confirmed, together with aggressive platelet and fibrinogen replacement. Risk is set by the white count at presentation, above 10 x 10^9/L being high risk.
ATRA, introduced in Shanghai in 1988, was the first differentiation therapy for any cancer; with anthracycline chemotherapy it lifted cure rates above 70 percent. Arsenic trioxide, developed in Harbin and Shanghai in the 1990s and approved in the United States for relapsed disease in 2000, degrades the fusion protein itself. The Italian-German APL0406 trial, reported in 2013, randomised low- and intermediate-risk patients to ATRA plus arsenic or ATRA plus chemotherapy: two-year event-free survival 97 percent versus 86 percent, with fewer infections and no secondary leukaemias, and the chemotherapy-free regimen became the standard, approved for first-line use in Europe in 2016 and the United States in 2018. High-risk patients receive ATRA and arsenic with an anthracycline or gemtuzumab ozogamicin added for the first weeks.
| Setting | Approach | Guideline |
|---|---|---|
| Suspected APL, first hours | Start all-trans retinoic acid on morphological suspicion; transfuse platelets and fibrinogen to targets; avoid invasive procedures until coagulopathy is controlled. | not mapped |
| Low- and intermediate-risk | All-trans retinoic acid plus arsenic trioxide induction and consolidation without chemotherapy (APL0406); dexamethasone prophylaxis or treatment for differentiation syndrome. | not mapped |
| High-risk | All-trans retinoic acid plus arsenic trioxide with idarubicin or gemtuzumab ozogamicin added during induction to control the white count. | not mapped |
| Molecular relapse | Arsenic-based salvage to molecular remission, then autologous transplant if PML::RARA negative, allogeneic transplant if not. | not mapped |