Absence of aberrant myeloid progenitors by flow cytometry is associated with favorable response to azacitidine in higher risk myelodysplastic syndromes

Abstract

Background: In intermediate-2 and high risk patients with myelodysplastic syndromes (MDS), treatment with azacitidine is associated with hematological responses and prolonged overall survival in patients who respond to therapy. However, only half of the patients that are treated will benefit from this treatment. It is a major challenge to predict which patients are likely to respond to treatment. The aim of this study was to investigate the predictive value of immunophenotyping for response to treatment with azacitidine of Int-2 and high risk MDS patients. Methods: Bone marrow aspirates were analyzed by flow cytometry in 42 patients with Int-2 and high risk MDS, chronic myelomonocytic leukemia or low blast count acute myeloid leukemia before treatment and after every third cycle of azacitidine. A flow score was calculated using the flow cytometric scoring system (FCSS). Results: The presence of myeloid progenitors with an aberrant immunophenotype was significantly associated with lack of response (p=0.02). A low pretreatment FCSS was associated with significantly better overall survival compared with a high pretreatment FCSS (p=0.03). A significant decrease in FCSS was observed in patients with complete response after three cycles azacitidine compared to patients with progressive disease (p=0.006). Conclusions: Absence of aberrant myeloid progenitor cells at baseline and/or a decrease in the FCSS during treatment identified Int-2 and high risk MDS patients who are likely to respond to treatment with azacitidine. © 2014 Clinical Cytometry Society.

Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes

“…Westers et al [48] showed that having aberrant progenitors negatively correlates with response to growth factor treatment. The same relation for response to azacitidine in intermediate-2 and high-risk MDS patients was shown [49]. Another interesting implementation for MFC is therapy monitoring.…”

Persistence of immunophenotypically aberrant CD34+ myeloid progenitors is frequent in bone marrow of patients with myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms treated with hypomethylating agents

“…Using this assay, we showed that aberrant CD34+ myeloblasts were persistently detected in about 85% patients, including patients who achieved HI as well as BM and cytogenetic response. Alhan et al 27 reported a similarly high frequency (79%) of persistent abnormal CD34+ myeloid precursors in their patients, although their study cohort contained a higher proportion of high-risk patients, including 12 (29%) AML with 20%–30% blasts. Craddock et al 28 showed that leukaemia stem cells (CD34+CD38−) were reduced substantially in patients with MDS who achieved CR, but were never eradicated; and expansion of this population of cells preceded morphological evidence of relapse.…”

“…In fact, in four patients the abnormalities were reduced to the level that the FCI findings became indeterminate for aberrancy. Interestingly, Alhan et al 27 found that mature myelomonocytic cells showed marked immunophenotypic improvement post-HMA treatment. We previously showed in CMML that HMA therapy led to a marked reduction of monocytes and improvement of myelomonocytic maturation despite the persistence of aberrant CD34+ myeloid progenitors 17.…”

TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients

“…A more robust predictor might be created by incorporating clinical findings or other biomarkers. 5,34,35 Indeed, the Groupe Français des Myélodysplasies has presented a clinically and cytogenetically based prognostic model for AZAtreated patients, although its predictive power is unclear. 5,6,36 As with these clinical measures, no mutations identified in our study were reliably strong predictors of primary resistance to treatment in a large number of patients.…”