Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML

Abstract

Objective: In individuals with cytogenetically normal (CN) AML, disease risk is estimated using molecular features such as the status of NPM1 and FLT3-ITD genes. However, data regarding the impact of NPM1 and FLT3-ITD status on hematopoietic stem cell transplant (HCT) outcomes are limited. We examined the effect of NPM1 and FLT3-ITD status on transplant outcomes in 131 CN AML patients transplanted at Princess Margaret Hospital between 2006 and 2017.

Methods: Overall survival (OS) was calculated using Kaplan-Meier analysis and multivariable Cox proportional hazards regression. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated using competing risk regression.

Results: There was no difference in 3-year OS among NPM1⁺ /FLT3-ITD^- , NPM1^- /FLT3-ITD^- , NPM1⁺ /FLT3-ITD⁺ and NPM1^- /FLT3-ITD⁺ patients: 56% (95% CI, 29%-76%), 61% (95% CI, 46%-73%), 53% (95% CI, 34%-70%) and 52% (95% CI, 17%-78%), respectively. CIR at 3-years was similar among NPM1^- /FLT3-ITD^- , NPM1⁺ /FLT3-ITD⁺ and NPM1^- /FLT3-ITD⁺ patients-14% (95% CI, 6%-26%), 13% (95% CI, 4%-28%) and 19% (95% CI, 4%-41%), respectively-while there were no relapses in the NPM1⁺ /FLT3-ITD^- group. NRM at 3 years for NPM1⁺ /FLT3-ITD^- , NPM1^- /FLT3-ITD^- , NPM1⁺ /FLT3-ITD⁺ and NPM1^- /FLT3-ITD⁺ patients was similar at 44% (95% CI, 19%-67%), 38% (95% CI, 25%-50%), 43% (95% CI, 25%-59%) and 44% (95% CI, 14%-71%), respectively.

Conclusion: NPM1 and FLT3-ITD status may provide limited prognostic information about transplant outcomes in CN AML patients.

Keywords: FLT3-ITD; NPM1; acute myeloid leukemia; cytogenetically normal; hematopoietic cell transplant.