White Blood Cell Count in Myelodysplastic Syndrome
There is no single "normal" WBC count for MDS patients—WBC values vary widely across the disease spectrum, ranging from severe leukopenia (<1.5 × 10⁹/L) to leukocytosis (>10 × 10⁹/L), depending on MDS subtype and presence of myeloproliferative features. 1, 2
WBC Count Patterns by MDS Subtype
Non-Proliferative MDS (Most Common)
- Most MDS patients present with normal to low WBC counts, typically with absolute neutrophil counts <1800/mcL defining cytopenia in prognostic scoring systems 1
- Severe leukopenia (WBC <1.5 × 10⁹/L) is an independent poor prognostic factor in refractory anemia subtypes 3
- Hypoplastic MDS specifically shows significantly lower peripheral WBC counts compared to normocellular/hypercellular variants 4
Chronic Myelomonocytic Leukemia (CMML) Variants
- Nonproliferative CMML: WBC ≤12,000/mcL (≤12 × 10⁹/L), classified within MDS spectrum for prognostic studies 1
- Proliferative CMML: WBC >12,000/mcL (>13 × 10⁹/L in 2017 classification), representing myeloproliferative overlap syndrome 1
- The 12,000/mcL cutoff is critical—proliferative CMML cases were specifically excluded from the International Prognostic Scoring System (IPSS) development cohort 1
MDS with Myeloproliferative Features
- Approximately 39% of MDS patients with isolated trisomy 8 develop myeloproliferative features, defined by repeated WBC >10 × 10⁹/L 5
- These cases show distinct molecular profiles (more EZH2, ASXL1, STAG2 mutations) and poorer response to hypomethylating agents 5
- The presence of leukocytosis does not exclude MDS diagnosis, particularly in overlap syndromes 2
Clinical Significance for Prognostication
IPSS Cytopenia Definition
- Absolute neutrophil count <1800/mcL defines neutropenia in the IPSS risk stratification system 1
- Number of cytopenias (0-1 vs 2-3) is one of three major independent variables determining survival and AML evolution risk 1
Prognostic Implications
- Lower WBC count (<1.5 × 10⁹/L) independently predicts worse survival in Chinese MDS-RA cohorts 3
- Hypoplastic MDS patients with lower WBC counts paradoxically have superior survival compared to normocellular MDS in low/intermediate-1 risk categories 4
- Elevated WBC with myeloproliferative features correlates with shorter event-free and overall survival 5
Diagnostic Screening Considerations
A novel MDS-CBC score incorporating absolute neutrophil count (along with MCV and neutrophil complexity) predicts MDS with 86% sensitivity and 88% specificity in cytopenic patients over age 50 6. This emphasizes that neutrophil count patterns, not just total WBC, are diagnostically relevant.
Critical Clinical Pitfalls
- Do not assume normal or elevated WBC excludes MDS—myeloproliferative features occur in substantial minorities of cases 2, 5
- Distinguish proliferative from nonproliferative CMML using the 12,000-13,000/mcL threshold, as this fundamentally changes classification and treatment approach 1
- Serial WBC monitoring is essential—myeloproliferative features may be acquired during disease evolution in up to 19% of initially non-proliferative cases 5
- Lower WBC in hypoplastic MDS does not necessarily indicate worse prognosis compared to higher counts in hypercellular disease 4