Leukemia-associated immunophenotypes subdivided in “categories of specificity” improve the sensitivity of minimal residual disease in predicting relapse in acute myeloid leukemia

Giovanni Rossi, Vincenzo Giambra, Maria M. Minervini, Chiara De Waure, Silvia Mancinelli, Michele Ciavarella, Nicola P. Sinisi, Potito R. Scalzulli, Angelo M. Carella, Nicola Cascavilla

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Abstract

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.

Original languageEnglish
JournalCytometry Part B - Clinical Cytometry
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Keywords

  • acute myeloid leukemia
  • categories of specificity
  • flow cytometry
  • leukemia-associated immunophenotypes (LAIPs)
  • minimal residual disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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