Panagiotis Tsirigotis, Maria Garofalaki, Ioanna Lazana, Maria Liga, Stavros Gigantes, Anastasia Kopsaftopoulou, Eirini Tziotziou, A Roumelioti, Eleni Tsintziloni, Stamatios Hatzis, Ioannis Konstantellos, Leonidas Benetatos, D. Barbarousi, Τατιάνα Τζένου, John Asimakopoulos, Aggeliki Karagiannidi, George Barakos, Sosana Delimpasi, Dionisios Stoumbos, Maria Stamouli, Eleni Plata, Krisela Valera, Stavroula Giannouli, Chrysovalantou Chatzidimitriou, Georgia Gkolfinopoulou, Marina P. Siakantaris, Maria Kotsopoulou, Michael Voulgarelis, Spiros Chondropoulos, Vasiliki Zina, Konstantinos Gkirkas, Eleni Kapsali, Charis Matsouka, Theodoros P. Vassilakopoulos, Alexandros Spyridonidis, Maria Angelopoulou, Ioannis Baltadakis
The prognostic value of NPM1-mut Measurable Residual Disease (MRD) has been increasingly recognized. However, real-world data validating the prognostic impact of NPM1-mut MRD remains limited. The aim of this study was to assess the prognostic value of NPM1-mut MRD and to explore optimal MRD thresholds for relapse prediction. One hundred forty-one patients with newly diagnosed NPM1-mut AML, from the Hellenic AML-Registry, in CR/CRi after the second cycle of induction and with bone marrow (BM) MRD assessment by RT-qPCR, were included in our study. Allogeneic stem cell transplantation (allo-SCT) in CR1 was not associated with any difference in RFS or OS between patients who achieved < 0.1% mutNPM1/ABL after the second cycle of chemotherapy, suggesting that this cut-off may effectively stratify relapse risk and possibly guide optimal use of allo-SCT. End-of-treatment (EOT) and during follow-up MRD assessment exhibited equally significant prognostic value, with high-level MRD positivity (≥ 0.1% mutNPM1/ABL) requiring early intervention to avoid imminent relapse, while those with undetectable or very low-level MRD (< 0.01% mutNPM1/ABL) being able to be safely monitored with no further intervention. Patients with low-level MRD positivity (≥ 0.01% and < 0.1%) require close MRD monitoring due to the substantial risk for progression to high-level MRD positivity. Overall, our results confirm the prognostic value of MRD assessment in BM samples at certain time points, with the cut-off of 0.1% after two cycles of chemotherapy enabling risk stratification and possibly informing transplant decisions, and during follow-up the cut-off of 0.01% being able to predict the 6-month relapse risk and guide further clinical management.