Outcomes of adult patients with Li-Fraumeni syndrome and myeloid neoplasms.

TP53

Germline TP53 variants, with myeloid neoplasms arising in carriers who had already had at least one neoplasm

Haematologic malignancies are not considered Li-Fraumeni syndrome defining tumours, although acute lymphoblastic leukaemia and therapy-related myeloid neoplasms have been described in the syndrome. Among 190 Li-Fraumeni syndrome patients followed between February 2001 and February 2026 with a history of at least one neoplasm, 14 (7%) developed a myeloid neoplasm, at a median age of 43 years (range 25-73), 11 of them female (79%). Eight patients had myelodysplastic syndrome (57%), five acute myeloid leukaemia (36%) and one T-myeloid mixed phenotype acute leukaemia (7%). With frontline therapy, 6 patients with myelodysplastic syndrome (75%) and 1 with acute myeloid leukaemia (17%) achieved an overall response, versus 75% and 83% respectively across all lines of therapy. At a median follow-up of 28.8 months, median overall survival was 18.2 months, with 1-year and 2-year survival rates of 77% and 17%; five patients underwent haematopoietic stem cell transplantation, with a median overall survival of 19.3 months.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The figure to retain is the collapse in survival between 1 year (77%) and 2 years (17%): responses do occur but do not hold, including after transplantation, and that is the number to keep in mind when discussing chemotherapy or radiotherapy in a TP53 carrier. Seven per cent of myeloid neoplasms among carriers who already had a cancer is a high proportion for a complication absent from the classical tumour spectrum, and to my mind it argues for haematological monitoring of treated carriers. Fourteen events in a single-centre series obviously cannot quantify a risk: these data describe a prognosis, they do not yet support a protocol.

Analysis by Dr Thibaut Benquey