8 modules on leukaemia: normal haematopoiesis, the four major types (AML, ALL, CML, CLL), the imatinib revolution in CML, BTK and BCL2 inhibitors in CLL, FLT3 in AML, CAR-T in B-ALL/DLBCL, allogeneic stem-cell transplant, and MRD-guided therapy.
Eight Modules
- Part I — Overview & Epidemiology: ~470 000 cases/yr globally, age-distribution by type (ALL pediatric peak, AML adult median 70, CLL elderly), Bennett 1845 / Virchow 1845 "leukämie".
- Part II — Normal Haematopoiesis: HSC hierarchy, lineage commitment, marrow niche, growth factors, key TFs (RUNX1, GATA1, PU.1, CEBPA).
- Part III — Acute Leukaemias (AML & ALL): Blast morphology, FAB historical / 2022 WHO/ICC genetic classification, key driver mutations (FLT3-ITD, NPM1, IDH1/2 in AML; Ph+, Ph-like, ETV6-RUNX1, MLL/KMT2A in ALL). PDB: BCR-ABL+imatinib, FLT3 kinase.
- Part IV — Chronic Leukaemias (CML & CLL): CML — Ph chromosome, three phases, the imatinib revolution. CLL — B-cell, IGHV mutated/unmutated, ZAP-70, del 17p, Rai/Binet staging. PDB: BTK + ibrutinib.
- Part V — Genetics & Molecular Drivers: Cytogenetics, Ph chromosome (Nowell & Hungerford 1960), translocations driving fusions, mutational landscape (TET2, DNMT3A, ASXL1; NOTCH1 in T-ALL; TP53 poor risk), CHIP. PDB: T315I + ponatinib.
- Part VI — Diagnosis: Blood smear, marrow aspirate/biopsy, flow cytometry, cytogenetics & FISH, NGS panels, qPCR for BCR-ABL, MRD assessment.
- Part VII — Therapy (flagship): AML 7+3, midostaurin/gilteritinib for FLT3+, venetoclax+aza for elderly. ALL multi-agent BFM/CALGB, blinatumomab BiTE, inotuzumab. CML TKIs (imatinib→ponatinib for T315I). CLL BTK inhibitors, BCL2 (venetoclax), anti-CD20. CAR-T (tisagenlecleucel for B-ALL).
- Part VIII — Stem-Cell Transplant & MRD: HLA matching, allogeneic vs autologous, conditioning regimens, GvHD vs GvL, MRD as the new endpoint, "operational cure" in CML, MRD-guided therapy future.
The course traces leukaemia from Virchow’s 1845 description to the 2017 approval of tisagenlecleucel (the first CAR-T) and beyond — arguably the most consistently transformed disease in oncology.