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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
  1. Lanshan Huang1,2,
  2. Guillermo Garcia-Manero3,
  3. Elias Jabbour3,
  4. Maitrayee Goswami1,
  5. Mark J Routbort1,
  6. L Jeffrey Medeiros1,
  7. Jeffrey L Jorgensen1,
  8. Sa A Wang1
  1. 1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
  3. 3Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Sa A Wang, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Unit 72, 1515 Holcombe Blvd, Houston, TX 77030, USA; swang5{at}mdanderson.org

Abstract

Aims Hypomethylating agents (HMAs) exhibit clinical efficacy in patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). This study was performed to assess residual disease status by flow cytometry immunophenotyping (FCI) methods in patients with MDS or MDS/MPN treated with HMAs, and correlate the findings with clinical response.

Methods CD34+ myeloid precursors were assessed in 85 patients with MDS and MDS/MPN treated with HMAs using FCI methods. Morphological, cytogenetic and molecular assessments were performed to evaluate the responses.

Results After a median six cycles (3–19) of HMAs, 40 (47%) patients showed haematological improvement, 26 (63%) showed bone marrow (BM) and 20 (39%) cytogenetic response. However, CD34+ myeloid progenitors showed persistent immunophenotypic aberrancies in 72 (85%) patients, indeterminate in four (5%) and negative in nine (10%). Compared with pretreatment BM in a given patient, FCI abnormalities were reduced in 15 (20%) patients, similar in 37 (48%), increased in 15 (20%) and showed antigenic shift in nine (12%). Patients who achieved immunophenotypic improvement had a superior progression-free survival (p=0.031). In the subgroup of patients who underwent haematopoietic stem cell transplant (HSCT), 16/19 (84%) patients who had a pre-HSCT positive FCI study became normal.

Conclusions These findings show the difficulty in eradicating neoplastic myeloid precursors by HMA therapy, thereby resulting in ultimate treatment failure in most patients. Achieving immunophenotypic improvement helps to identify patients who may benefit from continuous HMA treatment. HSCT provides a potential cure for these patients by replenishing BM with normal haematopoietic stem cells.

  • MYELOPROLIFERATIVE DISEASE
  • FLOW CYTOMETRY
  • STEM CELL TRANSPLANTS

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