Hematopoietic stem cell transplantation for severe congenital neutropenia

Hematopoietic stem cell transplantation (HCT) is the only curative option for patients with severe congenital neutropenia (SCN). Transplant success is dependent on identifying at-risk patients and proceeding to transplant before the development of severe infections or malignant transformation. This review focuses on recent advancements in risk stratification of SCN patients, indications for HCT, and review of published transplant studies.

Patients with poor neutrophil response despite high doses of granulocyte colony-stimulating factor (G-CSF) are at greatest risk for malignant transformation. Other studies demonstrate elevated risk with mutations in the G-CSF receptor gene and a specific mutation in the ELANE gene. These patients are at high-risk of sepsis or leukemia development and should proceed to transplant with best available donor. As recent published studies demonstrate, HCT is highly successful in patients without leukemia and, therefore, may be considered in selected low-risk patients given the life-long risk of malignancy and infection.

The decision whether to proceed to HCT in healthy patients maintained on G-CSF is difficult. As transplant-related mortality continues to decrease, the role of transplant in SCN is likely to expand to more patients.