The prognostic potential of monitoring disease dynamics in NPM1-positive acute myeloid leukemia
LEUKEMIA
Authors: Hoffmann, H.; Thiede, C.; Glauche, I.; Kramer, M.; Roellig, C.; Ehninger, G.; Bornhaeuser, M.; Roeder, I.
Abstract
Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML
EUROPEAN JOURNAL OF HAEMATOLOGY
Authors: Pasic, Ivan; Da'na, Waleed; Lam, Wilson; Law, Arjun; Lipton, Jeffrey H.; Viswabandya, Auro; Kim, Dennis D.; Thyagu, Santhosh; Messner, Hans A.; Michelis, Fotios V.
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.