Pre‐engraftment syndrome after unrelated donor umbilical cord blood transplantation in patients with hematologic malignancies

Abstract

Pre-engraftment syndrome (PES) after umbilical cord blood transplantation (CBT) remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcomes of PES in CBT recipients, who had been treated for hematologic malignancies at our transplantation center. PES was defined as unexplained fever higher than 38.3°C that is not associated with documented infection and unresponsive to antimicrobial manipulations and/or unexplained erythematous skin rash occurring prior to neutrophil engraftment. A total of 81 patients (median 18 yr, range 3-48) received either myeloablative (n=72) or non-myeloablative (n=9) conditioning. Neutrophil engraftment was achieved in 69 of the 81 cases [86.2%, 95% confidence interval (CI)=78.9-94.1%], and the median time to more than 0.5 × 10(9) /L ANC was 19 d (range, 12-39). Fifty-one patients (63.0%) developed PES at a median of 7d (range 3-15) post-transplant: 46 patients had both rash and unexplained fever; one patient had unexplained fever alone; and four patients had rash only. Forty-seven patients (92.2%) received IV methylprednisolone (MP) at a median dose of 1 mg/kg (range 0.4-3). All patients treated with MP responded as evidenced by fever resolution combined with resolution of rash. All patients with PES had high serum levels of C-reactive protein (CRP), which were significantly reduced after effective steroid treatment. Univariate analysis identified myeloablative conditioning and younger age as significant risk factors for developing PES. Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) in the PES+ and PES- groups was 51.5% (95% CI=38.0-70.0%) and 17.0% (95% CI=6.9-41.7%), respectively. In a multivariate analysis, we found significantly increased risk of grade II-IV aGVHD among PES patients (P=0.041). However, PES was not associated with sustained donor engraftment, the day to neutrophil recovery, chronic graft-versus-host disease, transplant-related mortality at day 180, and overall survival. Despite of the inherent limitations of this small retrospective study, PES seemed to be common after CBT and associated with high incidence of aGVHD.

Peri-engraftment syndrome in allogeneic hematopoietic SCT

“…[8][9][10][11] Although the pathogenesis was poorly understood, pre-ES could have developed long before neutrophil engraftment, of which the cumulative incidence was generally higher than that of ES, due to less stringent diagnostic criteria.…”

“…[2][3][4][5][6][7] Furthermore, pre-engraftment syndrome (pre-ES), which is more emphasized with a fever, rash and an occurrence in the pre-engraftment period, has been described and considered different from ES. [8][9][10][11] We retrospectively analyzed the clinical records of 176 patients following allogeneic HSCT. Furthermore, in a comparative study of the clinical features of pre-ES and ES patients, we found that both clinical syndromes were similar, which could be defined as a new entity of a clinical syndrome, termed as peri-engraftment syndrome (peri-ES).…”

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

“…[41][42][43][44][45][46] PES is reported after conventional and RIC transplants. Data are conflicting as to whether acute GVHD incidence is increased in persons with prior PES and whether PES influences NRM and survival.…”

Pulmonary manifestations of the pre-engraftment syndrome after umbilical cord blood transplantation

“…[7] Another study identified patients with PES as being at risk for both acute and chronic GVHD. [8] The use of cyclosporine for GVHD prophylaxis has been established as a risk factor for PES,[9] while the use of methotrexate for acute GVHD prophylaxis has been shown to reduce the incidence of early immune reactions after UCBT.…”