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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.

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.

journal_name

J Clin Pathol

journal_title

Journal of clinical pathology

authors

Huang L,Garcia-Manero G,Jabbour E,Goswami M,Routbort MJ,Medeiros LJ,Jorgensen JL,Wang SA

doi

10.1136/jclinpath-2016-203715

subject

Has Abstract

pub_date

2016-04-15 00:00:00

eissn

0021-9746

issn

1472-4146

pii

jclinpath-2016-203715

pub_type

杂志文章

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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.