General AML

Is there an effect for azacitidine on the survival and prognosis of MDS and AML patients with high bone marrow erythroblast frequency? A Japanese study

The classification of Acute Erythroid Leukemia (AEL), a rare form of Acute Myeloid Leukemia (AML) was previously characterized by a Bone Marrow (BM) erythroblast frequency of ≥50% together with a myeloblast percentage of > 20% among the non-erthyroid population in the 2008 World Health Organization (WHO) classification of Tumours of Hematopoietic Tissues.1 However, according to the revised 2016 WHO criteria, some cases of AEL have now been merged into the Myelodysplastic syndrome (MDS) with excess blasts classification. 2 This revision is a result of the overlap between AEL and MDS in terms of an erythroblast frequency of >50%. Nonetheless according to Uchida T. et al patients diagnosed with AEL have been reported to have a poorer prognosis.

The effect of azacitidine (AZA), a hypomethylating agent, on the survival outcomes of AEL ( based on the 2008 or the 2016 WHO classifications) and or Myelodysplastic Syndrome (MDS) patients with erythroblast frequency of ≥50% has not been elucidated.

In this study, Tomoyuki Uchida from the Eiju General Hospital, Japan and colleagues retrospectively analyzed MDS (n = 68, median age = 71 years) and AEL (n = 7, median age = 72 years) patients with a BM erythroblast frequency >50% and compared it to MDS patients with BM erythroblast frequency <50%. The patients were previously treated with AZA. The results were published in Leukemia Research on February 2017.

The key results are:
  • No significant difference observed in Hematological Improvement (HI)  and Complete Remission (CR) between AEL/MDS patients with erythroblast frequency of ≥50% and MDS patients erythroblast frequency of <50%
  • No significant difference observed in the median Overall Survival (OS) between AEL/MDS patients (n = 19) with erythroblast frequency of ≥50% and MDS patients (n = 42) erythroblast frequency of <50%; 15 vs 16 months
  • Median OS in patients with either erythroblast frequency <50% or ≥50%  that achieved HI was longer  compared to patients that did not achieve HI
  • Significant reduction of myeloblasts from 17% to 2% was observed in 1/3 patients in Complete Remission (CR)
  • There was no reduction of erythroblasts observed in patients that achieved CR (n = 3)

In summation, AZA is a promising therapeutic option for MDS and AEL patients regardless of the number of BM erythroblasts in these patients.

The authors highlighted that their findings contradicts previous studies, with no significant reduction in erythroblasts and a significant reduction of myeloblasts with AZA treatment in BM of patients.  The authors further suggested that inhibition of excessive erythropoiesis is not necessarily required to achieve a clinical benefit in AEL and MDS patients treated with AZA.

Abstract

We reviewed the cases of 68 consecutive patients who were diagnosed with myelodysplastic syndrome (MDS, n=61) or acute erythroleukemia (AEL, n=7) according to the World Health Organization (WHO) 2008 criteria and had previously been treated with azacitidine, a hypomethylating agent. Fifteen MDS patients had bone marrow erythroblast frequencies of ≥50%, and 6 out of the 7 AEL patients were reclassified as MDS (refractory anemia with excess blasts [RAEB]-1: 1, RAEB-2: 5) according to the revised WHO 2016 criteria. There was no difference between the overall response ratio (41%), as determined by a hematological improvement in at least one of 3 lineages, of these erythroid rich patients and that of the control group, which comprised 46 MDS patients with bone marrow erythroblast frequencies of <50%. Three MDS patients that exhibited erythroid predominance achieved complete remission. The overall survival period (median: 15 months) of the erythroblast-predominant group was not inferior to that of the control group (median: 16 months). These results indicate that azacitidine is a promising treatment option for MDS/AEL irrespective of the numbers of erythroid cells in the patient's bone marrow.

References
  1. Uchida T. et al. The effects of azacitidine on the response and prognosis of myelodysplastic syndrome and acute myeloid leukemia involving a bone marrow erythroblast frequency of >50. Leukemia Research. 2017 Feb; 53: 35-28. DOI: 10.1016/j.leukres.2016.11.012. Epub 2016 Nov 25
  2. Arber D.A.et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. May 2016 doi: 10.1182/blood-2016-03-643544
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