Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response

Leuk Lymphoma. 2016;57(4):812-9. doi: 10.3109/10428194.2015.1079318. Epub 2016 Mar 4.

Abstract

This study followed 28 patients with myelodysplastic syndromes (MDS) who showed a rise of bone marrow (BM) erythroids to ≥ 50% following three cycles (1-60) of hypomethylating agent (HMA) therapy. If BM blasts were calculated as a percentage of non-erythroids, 12 (42.9%) patients met the diagnostic criteria for acute erythroleukemia, erythroid/myeloid (AEL). However, none of the patients showed clonal cytogenetic evolution or new mutations. When compared to 47 de novo AEL patients, these 12 patients were less anemic and thrombocytopenic, had less complex karyotypes (p = 0.044) and showed a longer survival, either calculated from diagnosis (p < 0.001) or from the time of AEL (p = 0.005). These findings illustrate that ≥ 50% erythroids may appear in BM post-HMA therapy, likely a combination of reduction of BM granulocytes (p < 0.001) and promotion of normal or abnormal erythroid proliferation. Enumeration of blasts as a percentage of non-erythroid cells may lead to a diagnosis of AEL and mis-interpretation as disease progression.

Keywords: Acute erythroid leukemia; erythroid predominance; hypomethylating agents; myelodysplastic syndrome; therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Azacitidine / analogs & derivatives
  • Azacitidine / therapeutic use
  • Biopsy
  • Bone Marrow / pathology
  • Chromosome Aberrations
  • DNA Methylation / drug effects*
  • Decitabine
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Erythroblastic, Acute / diagnosis
  • Leukemia, Erythroblastic, Acute / etiology*
  • Leukemia, Erythroblastic, Acute / mortality
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Neoplasms, Second Primary / diagnosis
  • Neoplasms, Second Primary / etiology*
  • Neoplasms, Second Primary / mortality
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Decitabine
  • Azacitidine

Supplementary concepts

  • Acute erythroleukemia