Peri-engraftment Syndrome In Pediatric Hematopoietic Stem Cell Transplantation

This thesis includes two parts: Part I: Correlation of Peri-engraftment syndrome with clinical and laboratory factors in pediatric hematopoietic stem cell transplantation; Part II: Cytokines effect on Pre-engraftment syndrome after pediatric hematopoietic stem cell transplantion.PART I Correlation of Peri-engraftment syndrome with clinical andlaboratory factors in pediatric hematopoietic stem cell transplantationHematopoietic stem cell transplantation(HSCT) is the most important treatmet to cure malignant blood diseases, genetic diseases and congenital metabolic diseases in children. In recent years, as transplantation technology and family economic status have been much improved, HSCT becomes a common treatment in children.. Peri-engraftment syndrome is an early accompanying symptom of HSCT, characterized by non-infectious fever, non-drug lupus erythematosus, diarrhea, and/or jaundice and other clinical syndrome. The correlation remains to be illustrated of Peri-ES with clinical and laboratory factors and effects on the outcome. In this paper we respectrotively analyzed the correlated factors of peri-ES and the prognosis of peri-ES on the outcome of pediatric HSCT.Objective: To analyze the characteristics of Peri-ES and its correlation with clinical and laboratory factors and its outcome on overall survival after pediatric HSCT.Methods: Sixty two patients after HSCT were contunuously enrolled in this study between November 2010 and April 2010 in Children’s Hospital of Soochow University, including 56 cases with allo-HSCT, 5 cases with autologous HSCT, and one case with homogenic transplantation. Patients with allo-HSCT were further separated as sibling-matched HSCT(13cases),unrelated cord blood transplantation(CBT)(20 cases), and haploid identical HSCT(23 cases). Male to female was 37 to 25, Mmedian age was 8 years( 0.7 years to 16 years), and body weight 25 kg ranged from 7kg to 88 kg.We compared the correlation of peri-ES with HLA high resolution, KIR match fitness, blood type match fitness, transplanted types, preparative regimen and in vivo T cell depletion,and transplant complications, and its impact on oevrall survival.Results:1, Peri-ES occurred in 30 cases of 62 cases, the incidence rates were 76.19%, 52.17%, 8.33% for cord blood transplantation, haploid identical HSCT, and sibling matched HSCT, respectively. We didn’t observe peri-ES on autologous transplantation and homogenic transplantation The incidence of peri-ES patients with cord blood involved transplantation was higher than those with cord blood uninvovled(70% vs 9.1%, P<0.001).2,The body weight, HLA-DQ locus, donor source, preparative regimen based on BU/TBI+CY and GVHD prophylaxis with MTX showed a close correlation with peri-ES(P1<0.001, P2=0.006, P3<0.001, P4=0.014, P5=0.009). Blood type match fitness, KIR match fitness, TNC infused and in vivo T cell depletion didn’t show correlation with peri-ES.3, Patients with Peri-ES showed a higher incidence of acute GVHD with grade II to grade IV and bacterial infection(P1=0.0042, P2=0.036). Other events such as c GVHD(P=0.351), virus infection(P=0.146), fungal infection(P=0.141) and recurrence of disease(P=0.613) didn’t show any correlation with peri-ES. The neutrophil engraftment in patients with Peri-ES was same as patiehts without peri-ES(median time: 13 days vs 13.5 days, P=0.854) and same as the overall survivall(76.67% vs 90.63%,P=0.624).Conclusion: Incidence of Peri-ES was the highest in CBT, and second high in haploid identical HSCT, and positively correlated with the more body weight, HLA DQ, preparative regimen of BU/CY, GVHD prophylaxis with MTX, grade II to grade IV acute GVHD, and bacterial infection. Peri-ES did not affect overall survival.PART II Cytokines effect on Pre‐engraftment syndrome after pediatrichematopoietic stem cell transplantionPre-engraftment syndrome(PES) is an early accompanying symptom of HSCT, characterized by non-infectious fever, non-drug lupus erythematosus, diarrhea, and/or jaundice and other clinical syndrome. Up to now, the mechanism is not clear. It is generally accepted that a series of "cytokine storm" mediated the appearance of preengraftment syndrome. In this study, we detected the levels of IL-2, IL-6, TNF-α from the plasma of patients during PES.Objective: To explore the mechanisms of PES in hematopoietic stem cell transplantation, the levels of IL-2, IL-6, and TNF-α were detected during PES and their correlation with PES was analyzed.Methods: Ten patients with HSCT were selected, including four cases of CBT, five haploidentical HSCT(one case with bone marrow stem cells and peripheral blood stem cells, and 4 cases with bone marrow stem cells and peripheral blood stem cells and cord blood), one sibling-matched HSCT; 6 males and 4 females; aged 1.5 to 11 years, with a median age of 6.5 years; body weight ranged from 12 kg to 38 kg, with a median weight of 21 kg. Peripheral blood(EDTA anticoagulant 4ml)were collected at four time points(before stem cell infusion, one week, two weeks and three weeks after transplantation). The plasma was collected and preserved at-80 ℃refrigerator. ELISA method was employed to detect the levels of IL-2, IL-6, and TNF-α.Results: The plasma levels of IL-6 in PES group were(5.465±1.878) pg/ml,(22.140±4.899) pg/ml,(10.390±0.1475) pg/ml and(6.279±0.683) pg/ml at above four time-points, respectively. Plasma levels of IL-6 at two weeks after transplantation was significantly higher than the day of transplantation and three weeks after transplantation, and the difference was statistically significant(P1=0.0067, P2=0.0063). The plasma levels of IL-6 in patients without PES were(15.625±1.664) pg/ml,(10.868±5.383) pg/ml,(1.806±0.155) pg/ml,(3.609±1.427) pg/ml at above time-points respectively, which showed a tendency of decrease. The plasma levels of IL-2, TNF-α were not detected with the cytokine kits in these 10 cases.Conclusions: The plasma level of IL-6 had a transient rise during PES occurrence which implied that IL-6 plays a role in PES.