BACKGROUND: The assessment of minimal residual disease (MRD) by flow cytometry (FC) has a prognostic impact in acute myeloid leukemia (AML), despite the low sensitivity in predicting relapse. Nonetheless, the role of leukemic-associated immunophenotypes (LAIPs)-related specificity on the sensitivity of MRD has not been clarified yet. In this respect, we accomplished this study. METHODS: LAIP-frequencies of bone marrow samples from healthy donors and patients after treatment were quantified and subdivided in "categories of specificity" named as: "strong," "good," and "weak." At the following, the diagnostic performance of MRD was investigated in terms of sensitivity, specificity, predictive values, likelihood ratio (LR). RESULTS: "Strong" LAIPs were identified by CD7, CD2, CD4, and CD56 markers while "weak" LAIPs, independently of coexpressed markers, were mainly observed in CD33+ cells. MRD identified patients with significantly low DFS and OS but showed a low sensitivity in predicting relapse. Interestingly, majority of recurrences was noticed in patients with two LAIPs and lacking of "strong" LAIPs or only with one "good" LAIP. Thus, only patients showing one "strong" or two "good" LAIPs were considered suitable for MRD monitoring and selected to be further investigated. In this subset, positive MRD predicted a poor prognosis. Moreover, a higher sensitivity, negative predictive value (NPV) and LR- were observed after comparison with the previous series. CONCLUSIONS: These data highlight the relevant role of LAIP classification in "categories of specificity" in improving the sensitivity of MRD as assessed by FC.
BACKGROUND: The assessment of minimal residual disease (MRD) by flow cytometry (FC) has a prognostic impact in acute myeloid leukemia (AML), despite the low sensitivity in predicting relapse. Nonetheless, the role of leukemic-associated immunophenotypes (LAIPs)-related specificity on the sensitivity of MRD has not been clarified yet. In this respect, we accomplished this study. METHODS: LAIP-frequencies of bone marrow samples from healthy donors and patients after treatment were quantified and subdivided in "categories of specificity" named as: "strong," "good," and "weak." At the following, the diagnostic performance of MRD was investigated in terms of sensitivity, specificity, predictive values, likelihood ratio (LR). RESULTS: "Strong" LAIPs were identified by CD7, CD2, CD4, and CD56 markers while "weak" LAIPs, independently of coexpressed markers, were mainly observed in CD33+ cells. MRD identified patients with significantly low DFS and OS but showed a low sensitivity in predicting relapse. Interestingly, majority of recurrences was noticed in patients with two LAIPs and lacking of "strong" LAIPs or only with one "good" LAIP. Thus, only patients showing one "strong" or two "good" LAIPs were considered suitable for MRD monitoring and selected to be further investigated. In this subset, positive MRD predicted a poor prognosis. Moreover, a higher sensitivity, negative predictive value (NPV) and LR- were observed after comparison with the previous series. CONCLUSIONS: These data highlight the relevant role of LAIP classification in "categories of specificity" in improving the sensitivity of MRD as assessed by FC.
Authors: Michael Heuser; Sylvie D Freeman; Gert J Ossenkoppele; Francesco Buccisano; Christopher S Hourigan; Lok Lam Ngai; Jesse M Tettero; Costa Bachas; Constance Baer; Marie-Christine Béné; Veit Bücklein; Anna Czyz; Barbara Denys; Richard Dillon; Michaela Feuring-Buske; Monica L Guzman; Torsten Haferlach; Lina Han; Julia K Herzig; Jeffrey L Jorgensen; Wolfgang Kern; Marina Y Konopleva; Francis Lacombe; Marta Libura; Agata Majchrzak; Luca Maurillo; Yishai Ofran; Jan Philippe; Adriana Plesa; Claude Preudhomme; Farhad Ravandi; Christophe Roumier; Marion Subklewe; Felicitas Thol; Arjan A van de Loosdrecht; Bert A van der Reijden; Adriano Venditti; Agnieszka Wierzbowska; Peter J M Valk; Brent L Wood; Roland B Walter; Christian Thiede; Konstanze Döhner; Gail J Roboz; Jacqueline Cloos Journal: Blood Date: 2021-12-30 Impact factor: 22.113
Authors: Paula Piñero; Marina Morillas; Natalia Gutierrez; Eva Barragán; Esperanza Such; Joaquin Breña; María C García-Hernández; Cristina Gil; Carmen Botella; José M González-Navajas; Pedro Zapater; Pau Montesinos; Amparo Sempere; Fabian Tarín Journal: Cancers (Basel) Date: 2022-08-19 Impact factor: 6.575