Exploring the therapeutic effects of intensified immunosuppressive regimen for preengraftment syndrome after umbilical cord blood transplantation

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Preengraftment syndrome (PES) is a common complication of cord blood transplantation (CBT) that causes an inflammatory storm and organ impairments. Optimal treatment strategies for PES remain unclear.This study aims to explore the therapeutic effects of post-transplant cyclophosphamide (PTCy), etanercept, and methylprednisolone in the treatment of PES. This study included 60 patients who were diagnosed with PES after single umbilical cord blood transplantation between 2016 and 2023. Outcomes were compared between a historical control group (2016-2019, n = 27) treated with methylprednisolone and a cohort that received an intensified immunosuppressive regimen (2020-2023, n = 33) consisting of PTCy, etanercept, and methylprednisolone. The comparison encompassed key clinical outcomes, including hematopoietic engraftment, acute graft-versus-host disease (aGVHD), infection, relapse, and survival. Firstly, the intensified immunosuppressive regimen effectively alleviated the clinical symptoms of PES compared to the historical regimen, as evidenced by significantly higher rates of symptom resolution (fever remission: 75.7% vs. 44.4%, P = 0.006, rash remission: 57.5% vs. 29.6%, P = 0.042). It also reduced glucocorticoid exposure (median: 9 days [IQR 9-9] vs. 13 days [IQR 12-14], P < 0.001), and lowered the incidence of steroid tapering failure (6.1% ± 4.2% vs. 41.4% ± 9.6%, P < 0.001). Secondly, intensified immunosuppressive regimen was a protective factor against grade II-IV aGVHD (HR 0.239 [0.093-0.611], P = 0.008) and grade III-IV aGVHD (HR 0.259 [0.073-0.918], P = 0.036). However, it increased the risk of CMV/EBV infection (42.4% vs.18.5%, P = 0.043). Thirdly, the intensified immunosuppressive regimen had no effect on donor cell engraftment, the recurrence of malignant diseases or survival outcomes. The combination of PTCy, etanercept, and methylprednisolone represents an effective treatment strategy for PES and reduces the incidence of aGVHD, albeit with an increased risk of viral infections.

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