Supplementary file 1_Neutropenia (even mild) and anemia are poor prognostic factors in myelodysplastic syndromes.docx

BackgroundSevere neutropenia (ANC < 0.8 × 109/L) indicates poor MDS prognosis (IPSS-R classification). The impact of mild neutropenia is unclear.
MethodsWe compared baseline and outcomes (not infections) of 50 consecutive patients with neutropenia (Neutp, ANC < 1.5 × 109/L) to 50 non-neutropenic (Non-Neutp).
ResultsBoth groups were similar: Age 74.8 years; 61% males; ECOG 0/1 (91%); comorbidities. In Neutp vs. Non-Neutp patients: Hb (9.8 vs. 10.9 g/dL); WBC (2.7 vs. 7.7 × 109/L); Lymphocytes (1.2 vs. 1.8 × 109/L); Monocytes (0.46 vs. 0.73 × 109/L); PLT (115 vs. 201 × 109/L). Ferritin was higher (642 vs. 304 ng/mL, p = 0.002). BM dyserythropoiesis was less (50% vs. 72%, p = 0.04), while dysmyelopoiesis (48% vs. 26%) and blasts (3.3% vs. 1.1%, p < 0.001) were more common. More Neutp patients (60.0%) were classified as HR-IPSSR than Non-Neutp (12.2%, p < 0.001). The median OS was shorter (101 vs. 122 m, but p = 0.12); 18 (36%) Neutp vs. 6 (12%) Non-Neutp patients transformed to AML (p = 0.002), with a shorter TTL (p = 0.002). The median time to composite endpoint (death or leukemic transformation) was 82 vs. 114 m (p = 0.035). In a Cox proportional hazard model, CVD affected OS, while cytogenetics and neutropenia affected leukemic transformation and composite outcome. Lymphocytes, monocytes and platelets had no impact on outcomes. Patients with only neutropenia or only anemia (HB < 10) had a small, non-significant impact, but patients with both had a profound impact on all outcomes (composite: HR = 4.15, 95% CI [2.25–7.7], p < 0.001).
ConclusionMild neutropenia, especially with anemia, is a poor prognostic factor in MDS. These patients have more BM failure and worse outcomes (OS, leukemic transformation, TTL).