Quantification of minimal residual disease (MRD) reveals significant prognostic information in patients treated for acute myeloid leukemia (AML). The application of multiparameter flow cytometry (MFC) for MRD assessment has resulted in significant prognostic information in selected cases in previous analyses. We analyzed MRD in unselected patients with AML in complete remission (CR) after induction (n ‫؍‬ 58) and consolidation (n ‫؍‬ 62) therapies. By using a comprehensive panel of monoclonal antibodies we identified at least one leukemia-

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20–30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53–10.7) months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-014-2126-9) contains supplementary material, which is available to authorized users.

ObjectiveThe Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios.Patients and methodsThe sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed.ResultsIn this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001).ConclusionsIn this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.

Background: Multiparameter flow cytometry is increasingly used to monitor minimal residual disease in patients with acute myeloid leukemia to identify leukemic cells by leukemia-associated aberrant immunophenotypes (LAIPs). Changes in LAIPs during the course of the disease may be a limitation for this approach.Methods: We analyzed 49 patients at diagnosis and relapse by flow cytometry, cytomorphology, cytogenetics, and molecular genetics.Results: In 37 patients (76%), at least one LAIP detectable at diagnosis was present at relapse; in 12 patients (24%), none of the original LAIPs were present in at least 1% of bone marrow cells. Three groups were identified: no change in LAIPs, partial changes in LAIPs, and complete change in LAIPs. There were significant differences across these groups with regard to changes in cytomorphology (11%, 40%, and 58% of all cases, respectively; P ‫؍‬ 0.007), cytogenetics (15%, 20%, and 25%; not significant), and molecular genetics (18%, 0, and 86%; P ‫؍‬ 0.002).Conclusions: These data indicate that, in a subset of patients with acute myeloid leukemia, the disease is biologically different at relapse; therefore, monitoring of minimal residual disease is difficult to accomplish. In most patients with acute myeloid leukemia, multiparameter flow cytometry may be used to monitor minimal residual disease.

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