Peri-Engraftment Syndrome in Pediatric Allogenetic Hematopoietic Stem Cell Transplantationand the Effect of Methylprednisolone on Improving the Process of Peri-ES
Authors: Zheng De-fei , Wan Lin , LU Jun , Xiao Peifang , Bian Xin-ni , Zhai Zong , Hu Shaoyan 
Published: October 2019

Abstract

Objective and Purpose: Despite improvements in medical management, both engraftment syndrome (ES) and pre-engraftment syndrome (pre-ES) which were named as peri-engraftment (peri-ES)remain associated with severe morbidity and decreased the survival following hematopoietic stem cell transplantation (HSCT). Though many studies on peri-EShave been published in recent years, there is no report on the incidence of peri-ES and related factors in pediatric HSCT, Meanwhile, the intervention with MP on peri-ES remains controvertial.
Methods and patients: We retrospectively analyzed the data of 34 cases of pediatric allo-HSCT patients and the effect of methylprednisolone (MP) on the outcome of children with peri-ES transplanted between Nov 2010 and Dec 2013. The stem cell sources came from bone marrow alone [n=7], combining with peripheral blood [n=10], and cord blood alone [n=10], combining with bone marrow anf peripheral blood (n=7). Clinical characteristics and HSCT type were illustrated in Table 1 and 2. The incidence rate of peri-ES in cord blood transplantation (CBT), haploid transplants and sibling matched donor were 88.24%, 87.570% and 11.11%, respectively. All patients, who received either CBT or Hapolidentical SCT in conjunction of cord blood as the third part donor,developed peri-ES. We also identified that the peri-ES was highly associated with HLA disparity and mismatched ABO and aGvHD (Table 3 and 4).The median time of onset of peri-ES was 9 days after allo-HSCT. The most common symptoms of the peri-ES was eruthrodermous rash, followed by fever (Table 5). Twenty three children with peri-HSCT received intravenous MP at three doses of 0.5mg/kg, 1mg/kg, and 2mg/kg, respectively, based on the organs involved and the severity of peri-ES (Table 6). An excellent outcome was observed with relieving peri-ES in every patientand without influencingthe outcome of acute graft versus host disease (aGvHD), chronicgraft versus host disease (cGvHD), cytomegalovirus (CMV) infection, relapse, and overall survival (OS) with median follow up of xx months. (Table 4 and Figure 1 and 2).
Conclusion: Peri-ES is closely associated with the stem cell source with the sequence of CB, PB and BM. Meanwhile, disparity of HLA type and blood type mismatch also contributed to peri-ES. peri-ES caneasily proceeded into aGvHD. MP efficiently relieved the process of peri-ES without any significant adverse event or affecting theoutcome of HSCT and can be recommended to control peri-ES in this patient population.Table 1.The clinical and laboratory characteristics of HSCT patientsViable NumberAge (year)Median, range9(1-16)SexMale/female20/14Primary diseaseAcute myeloid leukemia17Acute lymphoblastic leukemia4Chronic myelogenous leukemia2Aplastic anemia8Myelodysplastic syndrome (monosome 7)1Juvenile myelomonocytic leukemia2Number of infused nuclear cellsCB Median (range), 107/kg4.8(1.2-9.6)Haplo Median (range), 108/kg10.65(7.2-14.39)Sibling Median (range), 108/kg9.6(6.48-18.66)Number of infused CD34+ cellsCB Median (range), 106/kg0.32(0.047-0.52)Haplo Median (range), 106/kg4.6(1.92-8.36)Sibling Median (range), 106/kg4.4(2.5-8.37)HLA matching(low resolution) of A, B, DR6/6(sibling or CBT)175/6(Haplo or CBT)74/6(Haplo or CBT)63/6(Haplo or CBT)4Table 2.Risk factors for peri-ESRisk factorsperi-ES group(n=23 )Non peri-ES group (n= 11)Totalperi-ES /Total(%) SourceBM0440BM+PB15616.67BM+PB+CB707100CB1521788.24 Transplantation typesibling18911.11unrelated1521788.24Haploid71887.50 sexMale1282060.00Female1131478.57 ABO compatibilitymatched991850.00mismatched1421687.50 HLA disparitymatched891747.06mismatched1521788.24Neutrophilengraftmentmedian+14+13.5STR(2W)median96.8%95.7%Table 3.The Effect of MP on HSCT complicationsOutcome 0.5mg/kg1mg/kg2mg/kgNon peri-ESP 1P 2Neutrophil engraftment(median day)+16+15+13.513.50.5320.478aGVHD4/85/76/82/110.5290.010cGVHD1/82/72/82/110.7251.000CMV infection4/85/76/87/110.5291.000Relapse1/80/70/82/110.4980.239
BM, bone marrow; CB, cord blood; PB, peripheral blood; HLA, human leukocyte antigen; STR on second week.
Note: P1: the comparison among three different doses of MP;
P2: A comparison between peri-ES group and non-peri-ES group.
Figure 1 Overall survival of pediatric allo-HSCT with and without peri-ES Figure 1. Overall survival of pediatric allo-HSCT with and without peri-ES

Disclosures
No relevant conflicts of interest to declare.