Prolonged granulocyte colony stimulating factor use in glycogen storage disease type 1b associated with acute myeloid...

Glycogen storage disease (GSD) type 1 is a rare autosomal recessive inherited condition. The 1b subtype comprises the minority of cases, with an estimated prevalence of 1 in 500,000 children. Patients with glycogen storage disease type 1b are often treated with granulocyte colony stimulating factor (G-CSF) for prolonged periods to improve symptoms of inflammatory bowel disease (IBD) and in the face of severe neutropenia to decrease risk of infection. Long-term G-CSF treatment may result in an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) possibly due to increased marrow stress resulting in telomere shortening. To our knowledge, there have been two published cases of AML in GSD type 1b patients following long-term G-CSF exposure. Here, we report two further cases of AML/MDS-related changes in patients GSD type 1b treated with G-CSF. One patient developed AML with complex karyotype after 20 years of G-CSF treatment. The second patient was found to have short telomeres after 10 years of G-CSF exposure, but no evidence of acute leukemia at present. The third patient developed AML/MDS after 25 years of G-CSF use, with short telomeres prior to bone marrow transplant. Together these cases suggest that GSD type 1b patients with prolonged G-CSF exposure may be at an increased risk of MDS/AML states associated with G-CSF-induced shortened telomeres. We recommend that any GSD1b patients with prolonged G-CSF should have routine telomere assessments with monitoring for MDS if telomere shortening is observed, and with particular attention warranted if there is unexplained loss of G-CSF responsiveness.