Consensus Opinion on Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis

Abstract

Advanced systemic mastocytosis (advanced SM), a rare disease closely associated with KIT mutations (most commonly KIT D816V), encompasses three variants: systemic mastocytosis (SM) with an associated hematologic clonal non-mast cell disorder, aggressive SM, and mast cell leukemia. All variants are associated with shortened survival. Although interferon-alpha or cladribine exhibit efficacy in selected patients, they do not result in cure. Imatinib is approved for the minority of aggressive SM patients with negative or unknown KIT D816V status. The multikinase/KIT inhibitor midostaurin is a promising agent for patients with advanced SM and is currently available on an investigational basis. We recently reported the largest retrospective study of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with advanced SM (n=57). The evidence from this study and a few case reports indicate that it can cure some patients and lead to long-term survival. However, there is still a significant gap of knowledge regarding the use of this high-intensity therapy in advanced SM. The present paper provides a consensus opinion on methods to optimize decision-making regarding the use of alloHCT in this patient population in light of currently available data. In addition, we outline strategies that combine midostaurin in the peritransplant setting. Such protocols should generate useful outcome data regarding the safety and efficacy of KIT inhibition in conjunction with high-intensity therapy in the treatment of advanced SM.