CD34+ Progenitor-Based Flow Cytometric Immunophenotypic Analysis Is Sensitive and Specific in Assessment of Myelodysplastic Syndromes.
Guilin Tang, Yi Zhou, Jeffrey L Jorgensen, Ying Hu, Kersh Marian, L Jeffrey Medeiros, Guillermo Garcia-Manero, Sa A Wang. MD Anderson, Houston, TX
Background: Flow cytometric immunophenotypic (FCI) assays of bone marrow (BM) have shown diagnostic utility in MDS patients. Most MDS FCI assays, however, are based on recognition of altered myelomonocytic maturation patterns. These patterns often become less reliable in patients undergoing various therapies. A CD34+ progenitor-based multicolor FCI assay is tested in cytopenic patients with the goal of identifying alternations in CD34+ cells that distinguish MDS from reactive cytopenias.
Design: A 7-color FCI assay was performed consecutively in patients in whom “rule out MDS” was requested from 5/2009 through 5/2010. A total of 147 patients with a confirmed diagnosis of MDS, and 112 patients with non-MDS cytopenia were included. The later group included patients who received chemotherapy, growth factors, immunosuppressive agents, or stem cell transplant for various conditions.
Results: Compared with non-MDS cytopenic patients, MDS patients had a higher number of total CD34+ cells (2.7 ± 0.26% vs 1.1 ± 0.1%), lower number of stage I hematogones (5.5 ± 1.1% vs 25 ± 2.1%) and plasmacytoid dendritic precursors (PDP) (3.5 ± 0.14% vs 6.4 ± 0.46%), p<0.001. Other significant alterations (p<0.01) included altered CD45/side scatter, increased expression of CD13, CD33, CD34, CD117, and/or CD123, decreased CD38, aberrant lymphoid antigens (CD2, CD5, CD7, and/or CD56) or mature myelomonocytic antigens (CD10, CD11b, CD15, CD16, CD64, and/or CD65) expression (Table 1). By defining “positive” as ≥ 1 aberrant lymphoid antigen or ≥ 2 significant alterations of other markers, the FCI assay to assess for MDS we present has a sensitivity of 90.5%; specificity of 88%; PPV of 91%; NPV of 88%, and an accuracy of 90%.
|Control (n=112)||MDS (n=147)||Sensi %||Speci %||Accu %|
|Stage 1 Hematogone (≤10%)||30||124||84||73||80|
|Mature myelomonocytic antigen||8||27||18||93||50|