title: 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.
authors.affiliation: Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China. wangxingbing91@hotmail.com
authors.forename: Xingbing
authors.initials: X
authors.lastname: Wang
authors.forename: Huilan
authors.initials: H
authors.lastname: Liu
authors.forename: Lailing
authors.initials: L
authors.lastname: Li
authors.forename: Liangquan
authors.initials: L
authors.lastname: Geng
authors.forename: Kaiyang
authors.initials: K
authors.lastname: Ding
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Tong
authors.forename: Weibo
authors.initials: W
authors.lastname: Zhu
authors.forename: Zimin
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D004890:Erythema / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005260:Female; D005334:Fever / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality / Q000628:therapy; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D009504:Neutrophils; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013577:Syndrome; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000893:Anti-Inflammatory Agents; D002097:C-Reactive Protein; D008775:Methylprednisolone