Alessia Fraccaroli, Vindi Jurinovic, Klaus Hirschbühl, Stauffer Elena, Katrin Koch, Stephan Breitkopf, Sarah Haebe, Heidrun Drolle, Maja Rothenberg-Thurley, Annika Dufour, Klaus H. Metzeler, Karsten Spiekermann, Marcus Hentrich, Andreas Hausmann, Mareike Verbeek, Christoph Schmid, Tobias Herold, Johanna Tischer
- Whether patients with acute myeloid leukemia (AML) harboring Nucleophosmin mutations (NPM1mut) with measurable residual disease (MRD) should undergo allogeneic stem cell transplantation (alloSCT) in complete remission (CR) remains subject of debate. This study aimed to assess whether the presence of bone marrow (BM) NPM1mut MRD, detected using a RT-qPCR assay with a sensitivity of 10-5, could influence the benefit derived from alloSCT. Data from four German transplantation centers were analyzed including 174 AML NPM1mut patients who underwent a first alloSCT between 2011-2022. Among 122 patients transplanted in complete remission (CR), pre-alloSCT MRD was positive in 54%. After alloSCT, the cumulative rate of BM MRD negativity increased from 65% by day +30 to 73% by day +100, with FLT3-ITD and ELN risk profile significantly impacting on MRD conversion rate at day +30. No significant difference in leukemia-free survival (LFS) and overall survival (OS) based on pre-transplant MRD statusWhether patients with acute myeloid leukemia (AML) harboring Nucleophosmin mutations (NPM1mut) with measurable residual disease (MRD) should undergo allogeneic stem cell transplantation (alloSCT) in complete remission (CR) remains subject of debate. This study aimed to assess whether the presence of bone marrow (BM) NPM1mut MRD, detected using a RT-qPCR assay with a sensitivity of 10-5, could influence the benefit derived from alloSCT. Data from four German transplantation centers were analyzed including 174 AML NPM1mut patients who underwent a first alloSCT between 2011-2022. Among 122 patients transplanted in complete remission (CR), pre-alloSCT MRD was positive in 54%. After alloSCT, the cumulative rate of BM MRD negativity increased from 65% by day +30 to 73% by day +100, with FLT3-ITD and ELN risk profile significantly impacting on MRD conversion rate at day +30. No significant difference in leukemia-free survival (LFS) and overall survival (OS) based on pre-transplant MRD status (3y LFS MRD+ 60% vs MRD- 74%, HR 1.5, p=0.28; 3y OS MRD+ 68% vs MRD- 78%, HR 1.42, p=0.39) was observed. Outcomes between MRD persistence and molecular relapse did not differ (p=0.8). Whereas adverse molecular risk features (HR 4.69, p=0.003) and relapsed/refractory disease (HR 2.83/3.59, p=0.005/0.001) were associated with unfavorable prognosis, administration of post-transplant maintenance improved survival in multivariable analysis (HR 0.48, p=0.06). Our findings suggest that in patients with NPM1mut AML MRD positivity as assessed per qPCR at time of transplant does not impact posttransplant outcomes of NPM1mut AML.…
