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

Abstract

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. 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. 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 3years 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. NPM1 and FLT3-ITD status may provide limited prognostic information about transplant outcomes in CN AML patients.