Leukemia-Associated Aberrant Immunophenotype (LAIP) in Patients with Acute Myeloid Leukemia (AML): Changes at Refractory Disease or First Relapse and Clinicopathological Findings
Wei Cui, Da Zhang, Mark Cunningham, Lowell Tilzer. The University of Kansas Medical Center, Kansas City, KS
Background: Multiparameter flow cytometry (MFC) is commonly used to detect minimal residual disease (MRD) during the course of chemotherapy or relapse for AML. Immunophenotypic changes have not been previously studied in refractory leukemia. In this study, we analyzed changes in LAIPs in AML patients between diagnosis and refractory/relapsed disease.
Design: We analyzed 41 patients at diagnosis and at refractory disease or first relapse by flow cytometry, morphology and cytogenetic studies.
Results: Thirty-six de novo and 5 therapy-related AML patients were included and there were 12 cases (29%) of refractory and 29 cases (71%) of relapsed leukemia. Ten patients (24%) shared all the LAIPs between diagnosis and refractory/relapsed disease, 3 patients (7%) showed completely changed LAIPs, while the rest of the patients (69%) showed partially changed LAIPs. LAIP changes from most to least frequent were as follows: altered CD13 (37%), altered CD33 (17%), altered CD14 (17%), gain of CD34 (12%), loss of CD56 (12%), and altered CD7 (12%). Cytogenetic clonal evolution at refractory/relapsed disease was observed in 20% of patients retaining all original LAIPs, 52% of patients with partially changed LAIPs and 33% of cases with completely changed LAIPs. Morphologically, only 6 patients (14%) including 3 patients with completely changed LAIPs showed significant changes at refractory/relapsed disease. Patients with refractory leukemia had an inferior survival compared to those with relapsed disease (median survival: 192 days vs. 381 days, p = 0.03) though no significant differences in aberrant CD7 or CD56 expression at diagnosis were observed between these two groups.
Conclusions: LAIP alterations during refractory/relapsed AML are common findings, which occur in 77% of our patients. Discordance between cytogenetic and LAIP changes suggests that gross cytogenetic clonal evolution during disease progression only partly contributes to immunophenotypic instability. The complexity of LAIP changes imposes a diagnostic challenge for detecting MRD during the course of treatment. Application of extended panels of antibodies will increase the sensitivity and accuracy in MFC-based MRD monitoring.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 224, Tuesday Morning