| Purpose1.To summarize the outcome and treatment of Graft Rejection of 337 p-thalassemia major(TM)patients who have experienced Hematopoietic Stem Cell Transplantion(HSCT)in the Pediatric Transplantation Center of Nanfang Hospital.2.Retrospectively evaluated outcomes of 30 paients with TM who recived donor lymphocyte infusion(DLI)for mixed chimerism(MC)level 1-3(donor<95%)after HSCT,and analysed the impact of the infusions timing and dosage of DLI on complications and effect in preventing Graft Rejection for patient with TM following HSCT.Method1.From June 2011 to June 2016,337 thalassemia major patients underwent HSCT in our Institution(the Pediatric Transplantation Center of Nanfang Hospital),Of them,195 patients are male,142 are female.Among the 337 patients,the median age at HSCT was 6(1.3-15)years old,of them,5 cases were received second transplantation because graft was rejected primarily or secondarily.Almost patients received NF-08-TM protocol as conditioning regimen.Observation was made at the engraftment time,chimerism level,and severity and time of GVHD after HSCT.2.Of the 337 patients with TM who received HSCT,50 patients had mixed chimerism.Risk of graft rejection will increase and DLI will be considered if donor derived cells continued to decline when we reduced the immuno-suppresion drugs.30 patients fitted with this status and received escalating doses of donor lymphocytes from the same donor.Patients were divided into four groups based on MC levels and received DLI or not:group ?,mixed chimerism-level-1(MCI,donor derived cells between 90%-95%)and didn' t receive DLI and just reduced the Immuno-suppresion drugs(n=20);group ?,MCI and received DLI(N=11);group ?,MC2(donor derived cells between 75%-90%)and received DLI(n=13);group ?,MC3(donor derived cells<75%)and received DLI(n=6).The patients of group ? were reduced calcineurin inhibitors(CSA)gradually and monitored chimerism consecutively;The patients of group ?-? received escalating doses of donor lymphocytes without CSA.The first dose of lymphocytes is 1-10×107/kg(recipient body weight),and the next DLI will be hold if the donor derived cells came back more than 95%.When donor derived cells still<95%and absence of GVHD and serious infection,the next DLI is given.After DLI,all patients were evaluable for graft function(chimerism,Hemoglobin,platelet levels)and GVHD.If GVHD occurred,relative treatment will be given according to GVHD severity.Result1.337 patients received 342 transplants.Of them,one patient had a primary rejection of graft,4 had secondary rejection,and these 5 patient received second transplantation.50 of them occoured mixed chimerism and 320 eases had foll donor-cell engraftment and thalassemia-free survival(TFS)finally.17 patients died,9 of them died of severe infection,4 died of severe GVHD,one died of eruptive myocarditis,one died of VOD,one died of intracranial hemorrhage caused by thrombocytopenia,and one died of pulmonary infection without getting timely medical care.95 patients had ?-? acute GVHD,12 ?-? acute GVHD,10 chronic GVHD.2.The conversion rates from mixed chimerism to complete chimerism in group ?to ? were 100%,100%,85%and 66.7%,respectively.2 patients occour graft rejection(GR)in group IV(33.3%).The incidence of GVHD in group ? to ? were 15%,27.3%,46.2%,and 33.3%,respectively.Compared group ? with ? the incidence of GVHD were 15%vs 213%(P=0.638).When comparison between first DLI timing,DLI before 180 days post-trasplant had significant high incidence of GVHD(50%)than those after 180(10%)(P=0.049).Compared with Cumulative dose of DLI,>1×107/kg group had high incidence of GVHD(50%)than?1×107/kg group(27.3%)but no significance of difference(P=0.142).Compared MSD-HSCT with UD-PBSCT,incidence of GVHD was 41%vs 25%(P=0.672).One patient in the group ? died of acute GVHD combined with severe infection.Conclusion1.The probabilities of survival,TFS,rejection,mixed chimerism and non-rejection mortality of thalassemia patients underwent HSCT were 95%,94.2%,1.5%,15%and 5%,respectively.The severe infection and GVHD are the important factors leading to death after transplantation.2.When patients with TM occour MC level-1 after HSCT,the taper or discontinuity of Immuno-suppresion drugs or along with DLI may be ferformed.Althought the both had the same effect but DLI group had higher incidence of GVHD,MCI patients should be preferred to adjust the Immuno-suppresion drugs strategy,3.MC level-2 and MC level-3 after HSCT is a great risk sign of GR,escalating doses of DLI from the same donor was effective in converting mixed chimerism to full donor chimerism.4.The first DLI timing is an important a factor to GVHD,and DLI before 180 days after transplantation will increase the incidence of GVHD.5.There was no significant difference in the cumulative dose of DLI to GVHD,but the small sample size may have influence on the statistical results. |
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