Background: Myeloid-derived suppressor cells (MDSCs), which include polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs), are known to suppress immune responses. Research on MDSCs following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancies is limited. This study aimed to characterize MDSCs and their pattern of immune reconstitution, as well as to explore the association between MDSCs and allo-HSCT outcomes in patients with hematologic malignancies.

Methods: Forty-one patients who underwent allo-HSCT at King Chulalongkorn Memorial Hospital from 2021 to 2023 were included. MDSCs were identified in whole blood using immunophenotyping with flow cytometry. Signature cytokines were measured using the Luminex assay. The percentage of MDSCs among total CD45 positive cells and cytokine levels were analyzed in relation to transplantation outcomes.

Results: Among the 41 patients, the median age was 44 years (range: 18-62), and they were diagnosed with acute myeloid leukemia (41.46%), acute lymphoid leukemia (36.59%), myelodysplastic syndrome (7.32%), myeloproliferative neoplasm (12.20%), and lymphoma (2.44%). Peripheral blood stem cells were collected from human leukocyte antigen-matched related/unrelated donors (82.93%) and haploidentical donors (17.07%). Thirty-seven patients (90.24%) received myeloablative conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitors plus methotrexate (68.29%) and post-transplant cyclophosphamide (31.71%). The median follow-up time was 188 days. Acute GVHD (aGVHD) occurred in 9 (21.95%) patients with a median onset time of 31 days, with only two patients experiencing grade II-IV aGVHD. The percentage of PMN-MDSC at day+14 and day+28 was significantly lower in aGVHD patients compared to non-GVHD patients (day+14: 0.0052% vs. 0.193%, p=0.003; day+28: 0.061% vs. 0.197%, p=0.018). Similarly, the CXCL2 level (a PMN-MDSC cytokine) was significantly lower in aGVHD patients. M-MDSC percentage and interleukin-10 (an M-MDSC cytokine) at day+28 were also significantly lower in aGVHD patients compared to non-GVHD patients (0.143% vs. 0.431%, p=0.023; 15.45 pg/ml vs. 25.07 pg/ml, p=0.011). Cytomegalovirus (CMV) reactivation was observed in 48.78% of patients, associated with increased M-MDSC at day+14 and decreased PMN-MDSC at day+14. For GVHD-free, relapse-free survival (GRFS) analysis, patients with high PMN-MDSC (≥0.15%) at day+14 had better outcomes than those with low PMN-MDSC (<0.15%) (95% CI: 1.102-9.706, p=0.030).

Conclusion: Delayed reconstitution of MDSCs at day+14 and day+28 post-allo-HSCT is associated with aGVHD occurrence. MDSCs could serve as potential surrogate markers for predicting aGVHD and CMV reactivation.

Disclosures

No relevant conflicts of interest to declare.

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2024
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