Abstract

Bloom’s syndrome (BS) is an inherited genome instability disorder caused by defects of the BLM helicase with extreme cancer predisposition. Here we report a girl with BS who developed acute lymphoblastic leukaemia (ALL) aged 9 and subsequently treatment-related acute myeloid leukaemia (AML) aged 12. The girl was born to a non-consanguineous white British couple. She had intrauterine growth retardation (Bwt 1.88Kg) and was followed up during infancy for faltering growth and dysmorphic features, but no definitive diagnosis was made. At 9 years of age old she was referred with unexplained bruising. A full blood count revealed pancytopenia and blast cells consistent with ALL, which led to the diagnosis of BS three weeks into treatment. She was treated on the ALL 2003 protocol with dose modifications for toxicity. Sixteen months after completion of ALL treatment she developed an aggressive secondary AML. In view of refractory disease and extreme toxicity treatment was discontinued after two courses of chemotherapy.

BS is a DNA fragility syndrome and affected individuals have a >50% risk of developing a malignancy. While the spectrum and frequency of malignancies in BS represents that in the general population, this is the first report of a paediatric patient developing AML following treatment for ALL. This girl was found to carry two novel BLM mutations, c.1221–1G > A and c.1624delG. This case documents the short interval at which treatment-related myeloid malignancy may occur in a child with BS and implies a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. It demonstrates the importance of molecular analysis in atypical cases of childhood malignancies. Novel approaches are required to improve treatment for these individuals as optimal dose delivery to often aggressive malignancies is hindered by extreme sensitivity to treatment toxicity.