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

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.

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

BACKGROUND: In intermediate-2 (Int-2) and high risk patients with myelodysplastic syndromes (MDS), treatment with azacitidine is associated with hematological improvement and prolonged overall survival (OS) in patients who respond to therapy. However, only half of the patients who 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 OS 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.

Azacitidine might be beneficial in a subgroup of older AML patients compared to intensive chemotherapy: a single centre retrospective study of 227 consecutive patients.

BACKGROUND: Treatment options in older acute myeloid leukaemia (AML) patients include intensive chemotherapy, best supportive care (BSC), and hypomethylating agents. Currently, limited data is available on hypomethylating agents in older AML patients in unselected patient populations. METHODS: To compare the effectiveness of azacitidine with conventional therapy, we collected data of 227 consecutive AML patients (≥60 years) who were treated with azacitidine (N = 26), intensive chemotherapy (N = 90), or BSC (N = 97). RESULTS: Azacitidine-treated patients were older and had more comorbidities, but lower white blood cell- and bone marrow blast counts compared with intensive chemotherapy patients. Complete or partial response was achieved in 42% of azacitidine-treated patients and in 73% of intensive chemotherapy patients (P = 0.005). However, the overall survival (OS) was similar (1-year-OS 57% versus 56%, P = 0.93; 2-year-OS 35% versus 35%, P = 0.92), and remained similar after correction for risk factors in a multivariate analysis. Patients treated with BSC had an inferior OS (1-year- and 2-year-OS 16% and 2%, P < 0.001). Compared to intensive chemotherapy, azacitidine-treated patients spent less days in the hospital (median in first three months 0.5 versus 56, P < 0.001), and needed less red blood cell and platelet transfusions (median per month 2.7 versus 7, P < 0.001 and 0.3 versus 5, P < 0.001) in the first three months. CONCLUSIONS: Azacitidine treatment is associated with a comparable OS but higher tolerability in a subgroup of older AML patients compared with intensive chemotherapy. Patients receiving BSC had a poor prognosis.

Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme.

The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified.