Assessment of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) before and after allogeneic hematopoietic stem cell transplantation in acute leukemia patients

Abstract

AbstractIn this monocentric prospective study, the influence on long‐term outcomes of peripheral blood levels of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) was investigated in 56 patients with acute leukemia (myeloid n = 47; lymphoid n = 9) before and after (Days+60/+90) allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). A risk of relapse was found to be associated with a level of pregraft M‐MDSC above 1.4% by ROC curve analysis. In multivariate analysis, this threshold retained a strong statistical significance (HR: 5.94 [2.09–16.87], p = 0.001). Considering only the group of patients who were in complete remission prior to Allo‐HSCT (n = 44), a significant prediction of relapse was found to be associated, in multivariate analysis, with a level of pregraft M‐MDSC above 1.4% (HR: 55.01 [14.95–202.37], p < 0.001) together with pregraft‐positive measurable ‐residual disease (MRD) (HR: 11.04 [1.89–64.67], p = 0.008). A poorer OS (HR: 6.05 [1.24–29.59], p = 0.026) and disease‐free survival (HR: 6.52 [1.41–30.19], p = 0.016) were also associated with higher levels of pregraft M‐MDSC. Remarkably, no relapse occurred in patients with pregraft‐negative MRD and ≤1.4% of M‐MDSC (vs. a 3‐year relapse rate of 60% for others, p = 0.004). Patients developing grade 3–4 acute graft‐versus‐host‐disease (GVHD, median occurrence: day+30 posttransplant) showed significantly higher levels of M‐MDSC% at days +60 and +90, suggesting a possible amplification of these immunosuppressive cells as a reaction to GVHD. In conclusion, this prospective study demonstrates a negative impact of higher proportions of peripheral M‐MDSC before Allo‐HSCT in leukemic patients. This paves the way to potential therapeutic intervention to decrease M‐MDSC levels before Allo‐HSCT and thus perhaps the incidence of relapse in such patients.