Development of Pre-Engraftment Syndrome, but Not Acute Graft-versus-Host Disease, Reduces Relapse Rate of Acute Myelogenous Leukemia after Single Cord Blood Transplantation

Abstract

The different effects of pre-engraftment syndrome (PES) and acute graft-versus-host disease (aGVHD) on outcomes after cord blood transplantation (CBT) are unclear. We retrospectively evaluated the impact of PES and aGVHD on relapse and survival after single-unit CBT in 138 adult patients with hematologic malignancies at our institution between 2004 and 2016. Multivariate analysis demonstrated that development of grade III-IV aGVHD, particularly with gut or liver involvement, significantly contributed to higher nonrelapse mortality (P < .001), but PES and grade II-IV aGVHD did not. In subgroup analyses of underlying disease type, the development of PES had a significant effect on decreased relapse (P = .032) and better disease-free survival (DFS) (P = .046) in patients with acute myelogenous leukemia (AML). These data suggest that PES is associated with a reduced relapse rate and better DFS in AML, indicating that the early immune reaction before neutrophil engraftment may provide a unique graft-versus-leukemia effect after single-unit CBT.

Clinical outcome of cord blood transplantation for nine children with juvenile myelomonocytic leukemia receiving fludarabine‐busulfan‐cyclophosphamide‐based conditioning

“…Although none has developed extensive chronic GVHD, PES has occurred in all eight engraft patients, and acute GVHD with grades Ⅰ–Ⅳ has occurred in six patients. Early immune reaction may be associated with the GVL effect in JMML after UCBT, confirming that the development of PES has a significant effect on the decreased relapse after UCBT for acute myeloid leukemia 25 . Notably, we withdrew the immunosuppressive agents within 4–6 months after UCBT, and the rapid taper of immunosuppression to enhance the GVL effects may prevent relapse in our study.…”

Identification of skin‐infiltrating donor lymphocytes in a case of pre‐engraftment syndrome

“…LETTER TO THE EDITOR from acute GVHD (aGHVD) and engraftment syndrome (ES), with reported incidence rates of 20%-86.6%. [1][2][3] aGVHD is a postengraftment alloreactive response mediated by donor-derived T cells that typically develops 14-100 days post-transplant. 4 ES occurs concomitantly with the emergence of peripheral neutrophils and is driven by cytokine production during early engraftment.…”

Umbilical Cord Blood Transplantation: Still Growing and Improving

“…However, heterogeneity of the conditioning regimens and specific GVHD prophylaxis strategies may account for the different ranges (20‐78%) of the reported incidences of PES. 106 , 107 , 108 , 109 …”

“…The pathogenesis and severity classification are still not clear; PES may be caused by cytokine storms associated with toxicities of the conditioning regimen, GVHD prophylaxis drugs, DMSO, G-CSF, or mismatched antigens by donor T cells. However, heterogeneity of the conditioning regimens and specific GVHD prophylaxis strategies may account for the different ranges (20-78%) of the reported incidences of PES [106][107][108][109].…”