Azacitidine Treatment of MDS/AML: Effect on Immunophenotyping by Flow Cytometry and Associated Cytogenetic Findings.
Alireza Torabi, James Z Huang, Vonda K Douglas-Nikitin, Marc D Smith. William Beaumont Hospital, Royal Oak, MI
Background: Azacitidine (AZA) has recently become a low-intensity treatment option in older patients with myelodysplasia/acute myeloid leukemia (MDS/AML). The antineoplastic activity of AZA differs from conventional chemotherapy due to its inihibition of DNA methyltransferase, likely causing hypomethylation of genes that play a role in MDS/AML pathogenesis. Yet, the exact mechanisms through which this process causes cell death/apoptosis in MDS/AML remain unclear. In this study we investigate flow cytometric immunophenotypic (FCI) changes in MDS/AML patients treated with an AZA-based regimen and the influence of cytogenetic (CYG) abnormalities at initial diagnosis.
Design: A pharmacy data base search at our institution from 2004-2010 revealed 47 patients who received AZA, 24 of which (10 patients with MDS and 14 with AML) had a follow-up bone marrow biopsy (BMBx) (median duration of 20 days for AML and 11 months for MDS). All 24 patients received AZA without standard induction chemotherapy, although a subset of AML patients did receive an AZA/Myelotarg combination. The initial and follow-up BMBx morphology, FCI and CYG data were reviewed. Fisher Exact test was used for statistical analysis.
Results: Patients who had follow-up BMBx consisted of 16 males and 8 females with a median age of 76. 3 patients (13%) showed complete or partial clinical remission (C/PCR; 1 MDS, 2 AML). Of these 3 patients, all showed significant response (SR) by FCI, including normalization of blast percentage and correction of antigenic dysmaturation. Examples of the latter include increase granulocyte side scatter and improved continuity of CD11b, CD13 and CD16 maturation patterns. Of patients who did not achieve C/PCR, flow cytometry showed no significant changes in 14 patients, decrease in blasts of >50% in 3, acquisition of a left shift with maturation arrest in 3 and SR in 1; 2 cases were suboptimal for analysis. There was a significant association between SR by FCI and clinical remission (p=0.003). CYG showed C/PCR was achieved in 1/4 cases with del 7, 0/3 with trisomy 8, 1/1 with trisomy 13, 1/6 with normal karyotype and 0/4 cases with complex karyotype.
Conclusions: 1) Of those patients with follow-up BMBx, the percentage of C/PCR is similar to that reported in the literature, 2) patients who improved clinically on AZA did show corresponding improvement by FCI, which include changes in side scatter, CD11b, CD13 and CD16, and 3) CYG abnormalities that impart a poor prognosis in patients with conventional care appear to have a similar affect in patients treated with AZA.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 160, Monday Morning