Engraftment syndrome after PD-1 blockade in classical Hodgkin lymphoma treated by autologous stem cell transplantation

Immune checkpoint inhibitors (CPIs) targeting PD-1, such as nivolumab and pembrolizumab, have become integral to the treatment of relapsed or refractory classical Hodgkin lymphoma (cHL), frequently serving as a bridge to autologous stem cell transplantation (ASCT). However, recent reports suggest that CPI exposure prior to ASCT may increase the risk of engraftment syndrome (ES), an inflammatory complication that emerges during neutrophil recovery. We present three cases of cHL treated by ASCT was performed following anti PD-1-based salvage therapy. Two of the three patients developed ES, with one case requiring high-dose corticosteroid pulse therapy due to severe respiratory symptoms. We examined lymphocyte counts and the interval between the final CPI dose and transplantation as potential contributing factors. While lymphocyte counts did not correlate with ES severity, the patient with the highest ES severity had the shortest CPI-to-transplant interval. These findings suggest that recent CPI exposure may contribute to ES, possibly via prolonged immune activation. As CPIs become more widely used in pre-ASCT regimens, clinicians should remain alert to the potential for delayed inflammatory toxicities and consider the timing of transplantation when planning post-CPI management strategies.