A multicenter retrospective comparison between systemic mastocytosis with t(8;21) AML and KIT mutant t(8;21) AML

Abstract

Concomitant systemic mastocytosis (SM) has been detected in a proportion of patients with AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 with KIT gene mutations [KITpos t(8;21) AML]. However, there are few reports summarizing characteristics of SM-t(8;21) AML due to its rarity. In this multi-center, retrospective study, we made the largest-to-date comparison of the clinical characteristics, molecular features and prognosis between SM-t(8;21) AML (n=24) and KITpos t(8;21) AML (n=212). In addition to higher mast cell burdens (p<0.001), lower platelet levels (p=0.001), higher variant allele frequency (VAF) in KIT mutations (34.00% vs 16.40%, p=0.008) and more KIT exon 17 mutations (34.70% vs 21.05%, p=0.025) were observed in SM-t(8;21) AML patients. Moreover, mutations at KITD816 (69.57% vs 45.75%, p=0.030), KITD816V (45.83% vs 27.83%, p=0.046) and DNMT3A (8.70% vs 0.96%, p=0.050) were more common in SM-t(8;21) AML. Compared to non-D816 KITpos t(8;21) AML, SM-t(8;21) AML and KITD816 t(8;21) AML were at higher risk of refractory/relapsed leukemia (26.4% vs 50.0% vs 50.0%, p=0.002) with dismal prognosis [2-year OS: 79.2% vs 34.7% vs 60.7%, p=0.004; 2-year EFS: 61.7%vs 36.2% vs 39.7%, p=0.012]. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could only improve prognosis of SM-t(8;21) AML patients. For all patients in our cohort, age > 60 years, KITD816 mutations and BCOR mutations were showed to be independent unfavorable predictors for OS and EFS. Our results revealed that SM-t(8;21) AML shared more similar clinical characteristics, molecular features and clinical outcomes with KITD816 t(8;21) AML.