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 patients

Viable Number
Age (year)  
Median, range 9(1-16) 
Sex  
Male/female 20/14 
Primary disease  
Acute myeloid leukemia 17 
Acute lymphoblastic leukemia 
Chronic myelogenous leukemia 
Aplastic anemia 
Myelodysplastic syndrome (monosome 7) 
Juvenile myelomonocytic leukemia 
Number of infused nuclear cells  
CB Median (range), 107/kg 4.8(1.2-9.6) 
Haplo Median (range), 108/kg 10.65(7.2-14.39) 
Sibling Median (range), 108/kg 9.6(6.48-18.66) 
Number of infused CD34+ cells  
CB Median (range), 106/kg 0.32(0.047-0.52) 
Haplo Median (range), 106/kg 4.6(1.92-8.36) 
Sibling Median (range), 106/kg 4.4(2.5-8.37) 
HLA matching(low resolution) of A, B, DR  
6/6(sibling or CBT) 17 
5/6(Haplo or CBT) 
4/6(Haplo or CBT) 
3/6(Haplo or CBT) 
Viable Number
Age (year)  
Median, range 9(1-16) 
Sex  
Male/female 20/14 
Primary disease  
Acute myeloid leukemia 17 
Acute lymphoblastic leukemia 
Chronic myelogenous leukemia 
Aplastic anemia 
Myelodysplastic syndrome (monosome 7) 
Juvenile myelomonocytic leukemia 
Number of infused nuclear cells  
CB Median (range), 107/kg 4.8(1.2-9.6) 
Haplo Median (range), 108/kg 10.65(7.2-14.39) 
Sibling Median (range), 108/kg 9.6(6.48-18.66) 
Number of infused CD34+ cells  
CB Median (range), 106/kg 0.32(0.047-0.52) 
Haplo Median (range), 106/kg 4.6(1.92-8.36) 
Sibling Median (range), 106/kg 4.4(2.5-8.37) 
HLA matching(low resolution) of A, B, DR  
6/6(sibling or CBT) 17 
5/6(Haplo or CBT) 
4/6(Haplo or CBT) 
3/6(Haplo or CBT) 
Table 2.

Risk factors for peri-ES

Risk factors  peri-ES
group(n=23 ) 
Non peri-ES
group (n= 11) 
Total peri-ES /
Total(%) 
Source BM 
BM+PB 16.67 
BM+PB+CB 100 
CB 15 17 88.24 
Transplantation type sibling 11.11 
unrelated 15 17 88.24 
Haploid 87.50 
sex Male 12 20 60.00 
Female 11 14 78.57 
ABO compatibility matched 18 50.00 
mismatched 14 16 87.50 
HLA disparity matched 17 47.06 
mismatched 15 17 88.24 
Neutrophilengraftment median +14 +13.5   
STR(2W) median 96.8% 95.7%   
Risk factors  peri-ES
group(n=23 ) 
Non peri-ES
group (n= 11) 
Total peri-ES /
Total(%) 
Source BM 
BM+PB 16.67 
BM+PB+CB 100 
CB 15 17 88.24 
Transplantation type sibling 11.11 
unrelated 15 17 88.24 
Haploid 87.50 
sex Male 12 20 60.00 
Female 11 14 78.57 
ABO compatibility matched 18 50.00 
mismatched 14 16 87.50 
HLA disparity matched 17 47.06 
mismatched 15 17 88.24 
Neutrophilengraftment median +14 +13.5   
STR(2W) median 96.8% 95.7%   
Table 3.

The Effect of MP on HSCT complications

Outcome  0.5mg/kg 1mg/kg 2mg/kg Non peri-ES P 1 P 2 
Neutrophil engraftment
(median day) 
+16 +15 +13.5 13.5 0.532 0.478 
aGVHD 4/8 5/7 6/8 2/11 0.529 0.010 
cGVHD 1/8 2/7 2/8 2/11 0.725 1.000 
CMV infection 4/8 5/7 6/8 7/11 0.529 1.000 
Relapse 1/8 0/7 0/8 2/11 0.498 0.239 
Outcome  0.5mg/kg 1mg/kg 2mg/kg Non peri-ES P 1 P 2 
Neutrophil engraftment
(median day) 
+16 +15 +13.5 13.5 0.532 0.478 
aGVHD 4/8 5/7 6/8 2/11 0.529 0.010 
cGVHD 1/8 2/7 2/8 2/11 0.725 1.000 
CMV infection 4/8 5/7 6/8 7/11 0.529 1.000 
Relapse 1/8 0/7 0/8 2/11 0.498 0.239 

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

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Disclosures

No relevant conflicts of interest to declare.

Author notes

*

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