Peri-engraftment syndrome in allogeneic hematopoietic SCT

Abstract

Engraftment syndrome (ES) and pre-engraftment syndrome (pre-ES) are both inflammatory conditions that occur after hematopoietic SCT (HSCT) and are characterized by non-infectious fever and skin rash. Although the pathogenesis is not fully understood, both syndromes are similar, and could be defined as a new clinical syndrome, named as peri-engraftment syndrome (peri-ES). We retrospectively analyzed the clinical records in 176 pediatric patients, following allogeneic HSCT. We utilized the definition of ES by Spitzer as the diagnostic criteria, excluding 'within 96 h of engraftment' criteria. Thirty cases developed peri-ES with a cumulative incidence of 17.0%. High cumulative incidence (50%) was seen in patients who underwent a double-unit cord blood transplantation (DUCBT; Po0.01). Clinical findings of peri-ES are similar, regardless of the onset day, and encephalopathy was the most severe complication. In the DUCBT cohort, the use of TBI and early complete chimerism (pday 21) were identified as risk factors that predispose the development of peri-ES. We determined that both, ES and pre-ES, might have similar causes, which could be included in peri-ES. Particularly, it occurred more in DUCBT patients, which means that not only neutrophil engraftment but also immune reactions within the two units might contribute to peri-ES.

Prognostic factors and outcomes for pediatric patients receiving an haploidentical relative allogeneic transplant using CD3/CD19-depleted grafts

“…Although the pathogenesis is not fully understood, both syndromes are similar, and could be defined as a new clinical syndrome, named as peri-ES. 13 Although this complication has been previously reported in a pediatric transplantation setting, there are no reported data regarding ES in haploidentical pediatric transplantation. The reported incidence of ES in children ranges from 19% to 48% and has been considered a risk factor for developing aGvHD and cGvHD.…”

“…We were not able to identify risk factors for engraftment failure because of the low number of patients. The median time to neutrophil recovery for the patients with engraftment was 13 days (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The median time to platelet engraftment was 10 days (8-70), and the median times to platelet counts of 50 × 10 9 /L and 100 × 10 9 /L were 13 days (9-150) and 15 days (9-150), respectively.…”

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

“…13,30,31 Schmid et al 13 reported a 48% incidence of ES. Amphotericin treatment and more mononuclear cells in the graft were associated with an increased risk of ES in multivariate analysis.…”

“…Risk factors for ES included age o8 years and transplants from an HLA-mismatched donor. Hong et al 31 used the Spitzer criteria to characterize a periengraftment syndrome after allotransplants. A cumulative ES incidence of 17% was reported with the highest incidence among recipients of double-unit umbilical cord blood transplants, in whom use of total body radiation in the conditioning regimen and early complete chimerism were also risk factors.…”

Engraftment Syndrome: An Updated Review

“…However, it has remained poorly characterized with unclear prognosis or appropriate therapy [20,35]. Several recent studies on PES have come to the following conclusions: (1) common occurrence after UCBT, (2) development before neutrophil recovery, (3) associations with: cyclosporine in GVHD prophylaxis and total body irradiation in conditioning therapy, (4) enhancement of engraftment without significant morbidity as well as early achievement of complete donor chimerism, and (5) controversial association with development of acute GVHD [20,[36][37][38]. -Skin rash -Pulmonary infiltrates -Diarrhea commencing 24 hours before or at any time after the first appearance of neutrophils (1) GVHD prophylaxis using methotrexate in UCBT, (2) use of cyclophosphamide and prednisolone in induction followed by cyclophosphamide mobilization in patients with POEM syndrome, (3) use of donor lymphocyte infusions in relapsed CML after allogeneic HSCT, and (4) steroid prophylaxis significantly decreases the risk of ES following autologous HSCT and is associated with shortened hospitalization without increasing the risk of infection [42][43][44][45].…”