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.
Viable . | Number . |
---|---|
Age (year) | |
Median, range | 9(1-16) |
Sex | |
Male/female | 20/14 |
Primary disease | |
Acute myeloid leukemia | 17 |
Acute lymphoblastic leukemia | 4 |
Chronic myelogenous leukemia | 2 |
Aplastic anemia | 8 |
Myelodysplastic syndrome (monosome 7) | 1 |
Juvenile myelomonocytic leukemia | 2 |
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) | 7 |
4/6(Haplo or CBT) | 6 |
3/6(Haplo or CBT) | 4 |
Viable . | Number . |
---|---|
Age (year) | |
Median, range | 9(1-16) |
Sex | |
Male/female | 20/14 |
Primary disease | |
Acute myeloid leukemia | 17 |
Acute lymphoblastic leukemia | 4 |
Chronic myelogenous leukemia | 2 |
Aplastic anemia | 8 |
Myelodysplastic syndrome (monosome 7) | 1 |
Juvenile myelomonocytic leukemia | 2 |
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) | 7 |
4/6(Haplo or CBT) | 6 |
3/6(Haplo or CBT) | 4 |
Risk factors | peri-ES group(n=23 ) | Non peri-ES group (n= 11) | Total | peri-ES / Total(%) | |
Source | BM | 0 | 4 | 4 | 0 |
BM+PB | 1 | 5 | 6 | 16.67 | |
BM+PB+CB | 7 | 0 | 7 | 100 | |
CB | 15 | 2 | 17 | 88.24 | |
Transplantation type | sibling | 1 | 8 | 9 | 11.11 |
unrelated | 15 | 2 | 17 | 88.24 | |
Haploid | 7 | 1 | 8 | 87.50 | |
sex | Male | 12 | 8 | 20 | 60.00 |
Female | 11 | 3 | 14 | 78.57 | |
ABO compatibility | matched | 9 | 9 | 18 | 50.00 |
mismatched | 14 | 2 | 16 | 87.50 | |
HLA disparity | matched | 8 | 9 | 17 | 47.06 |
mismatched | 15 | 2 | 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 | 0 | 4 | 4 | 0 |
BM+PB | 1 | 5 | 6 | 16.67 | |
BM+PB+CB | 7 | 0 | 7 | 100 | |
CB | 15 | 2 | 17 | 88.24 | |
Transplantation type | sibling | 1 | 8 | 9 | 11.11 |
unrelated | 15 | 2 | 17 | 88.24 | |
Haploid | 7 | 1 | 8 | 87.50 | |
sex | Male | 12 | 8 | 20 | 60.00 |
Female | 11 | 3 | 14 | 78.57 | |
ABO compatibility | matched | 9 | 9 | 18 | 50.00 |
mismatched | 14 | 2 | 16 | 87.50 | |
HLA disparity | matched | 8 | 9 | 17 | 47.06 |
mismatched | 15 | 2 | 17 | 88.24 | |
Neutrophilengraftment | median | +14 | +13.5 | ||
STR(2W) | median | 96.8% | 95.7% |
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.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
This icon denotes a clinically relevant abstract