| Objective:The relation of the recovery of T lymphocytes and the immune system reconstruction,Graft versus host disease(Graft versus host diseases,GVHD)recurrence and infection after allogeneic hematopoietic stem cell transplantation are closene.Under normal circumstances,CD4 +T cells not only auxiliary killing tumor cells,CD8 + T cells can also assist in NK cells removed and kill tumor,play an important role in restraining tumor immune.The initial T cells perform the function of immune surveillance through recycling.Memory T cell response is several times the initial T cells,and more quickly and efficiently in antigen intensity.Treg cells play an important role in adjustment tumor immunity,prevention of autoimmune diseases,and inducing transplantation tolerance with immune incompetent and immunosuppressive properties.This study observed a period of 12 months after allo-HCST about the recovery CD4 + T lymphocyte subgroup with the correlation of GVHD,recurrence and infection and so on.Methods:1 Retrospective analysis of the number of 35 patients underwent allo-HSCT from 2014-2 to 2015-11,in the Blood and Marrow Transplanation Center,Department of Hematology,The Second Hospital of Hebei Medical University.2 The clinical condition of patients.Age:the median age of patients was 31 years old(3-56 years old).Gender:19 cases were femal,16 cases were male.Diagnosis and staging:23 cases were AL(15 of them were CR1,7 of them were more than CR2,1 case was NR),4 cases were MDS(all of them were MDS-RAEB,Revised International prognostic scoring system(IPSS-R): all of them were high risk),7 cases was SAA,1case was aCML.Observation off time:2015-11-31.Transplantation mode:14 cases underwent MSD,2 cases underwent MUD,19 cases underwent Haplo-HSCT.Unrelated donors use peripheral stem cells,haplo-HSCT/MSD use bone marrow and peripheral stem cells or peripheral stem cells.Preparative regimen:People with hematological malignancies use modified BU+CY or BU+CY+ATG/ATG-F,people with aplastic anemia use CTX+ATG+BU ± ATG.Prevention of GVHD are MMF?CSA and short-term MTX;the average number of stem cells:MNC5.76*108/Kg(Recipient weight),CD34+ 7.08*106/Kg(Recipient weight);Healthy controls were 25 healthy donors.Sample collection:at the time of 1,2,3,4.5,6,9,12 months after transplantation,collected EDTA anticoagulated peripheral blood 4ml.The control group collected peripheral blood before using G-CSF.3 FACS Cantoll ? flow cytometry was used to analyse CD4+T subgroup cells changes.Antibody combination: CD4+T lymphocyte:CD3/CD4,naive CD 4+T lymphocyte:CD3/CD4/CD62L/CD45RA/CD45RO?memory CD4+T lymphocyte:CD3/CD4/CD45 RO ? regulatory CD4+T cell:CD3/CD4/CD25/FoxP3,Measurement data apply two independent sample t-test.Results:1 33 of the patients had rapid hematopoietic resconstitution.The time when absolute neutrophil counts(ANC)were more than 0.5×109/L were11.45±1.44 days,the time of platelet count more than 20×109/L were13.21±3.56 days.2 After transplantation,35 cases have different levels of infection,12 cases of pulmonary infection,the incidence is 34.29%;15 cases of them infection CMV and the incidence was 42.86%.10 cases died(28.57%),of which the primary disease recurrence 4 cases(11.43%),severe aGVHD 4(11.43%),2 cases of death were becaose of systemic inflammatory response syndrome and pulmonary infection.3 Recovery of CD4+T subgroup cells3.1 CD4+T cells:The variation of CD4+T subgroup after Allo-HSCT +1?+6?+12months is a slow procss.CD3+CD4+ cells count recover slowly in transplantation group,at 1 month after transplantation it was lower than that in control group(297.33±195.59/ul vs 912.80±323.27/ul,P <0.001),at 6 months(405.00±214.90/ul vs 912.80±323.27/ul,P<0.001),at12 months after transplantation it was still below than that in control group(480.00±169.82/ul vs 912.80±323.27/ul,P=0.009),it about reached half of the normal.3.2 Treg cells:Treg cells count in transplantation group need long time,at1month(5.54±3.05/ul vs 20.83±17.62/ul,P < 0.001),at 9 months the transplantation group to achieve the 50% of normal(9.57±3.25/ul vs20.83±17.62/ul,P < 0.001),at 12 months after transplantation was still significantly lower than that in control group(12.87±3.02/ul vs20.83±17.62/ul,P=0.032).3.3 Naive CD4+T cells:Naive CD4+T cells count recovery extremely slowly,at 1month(7.49±5.71/ul vs 283.48±189.75/ul,P < 0.001),at 2-3months Gradually reduce,at 3 months the counts reach the lowest(4.58±3.00/ul vs 283.48±189.75/ul,P<0.001),then at 6 months it gradually grow to(6.88±3.70/ul vs 283.48±189.75/?l,P<0.001),until 12 month after transplantation it were still lower than that in control group(28.05.±26.42/?l vs 283.48±189.75/?l,P<0.001),abou one over ten of the control group.3.4 Memory CD4+T cells:Memory CD4+T cells recover relatively fast,at1month(172.71±122.73/ul vs 532.00±165.25/ul,P<0.001),at 6 months the transplantation group to achieve the 50% of normal(265.00±85.15/ul vs 532.00±165.25/ul,P<0.001),in 12 months after transplantation still lower than that in control group(361.67±121.89/ul vs532.00±165.25/ul,P=0.003).4 Recovery of CD4+T subgroup cells associated with acute GVHD.In100 days after transplantation,6 of the 35 patients(17.14%)developed severe aGVHD.In the absolute number of CD4+T subgroup cells inpatients with aGVHD were significantly lower than that in those without severe aGVHD(P<0.05),it reminder that the rebuilding delay CD4 + T cells,Treg cells,initial CD4 + T cells may be lead to aGVHD factors,and memory CD4 + T cells did not reduce aGVHD occurred(Since the cases were small,we didn't make analyse).5 Recovery of CD4+T subgroup cells and the possibility of relapse.6 of35 patients were recurrenced(17.14%),4 of them were Recurrence of hematology,respectively occur at 31,61,156,170 days after transplantation.The rest 2 cases were molecular relapse,time were at 60,274 days.The Treg,memory CD4 + cells in front of the recurrence monitoring above average,it may be reminder the positive correlation associated with recurrence;The initial CD4 + cells,by contrast,the monitoring point before relapse below the average.Because of the number of cases less,do not make statistical processing.6 Recovery of CD4 + T lymphocyte subsets with ATG At 1 to 3 months after transplantation,Pretreatment scheme used ATG in patients,HLA in all patients(n = 5)with HLA in half patients(n = 16),monitoring 1-3months of CD4 + T lymphocyte subgroup,found HLA in all patients after transplantation CD3 +CD4,Treg cells,initial CD4 + T cells,and memory CD4 + T cells is higher than the haplo-HSCT;both groups the navie CD4+T cells trend are decline.CD4+T subgroup cells have significantly difference between HLA in all patients and haplo-HSCT(P<0.05).it may present that HLA in all transplantation immune recovery relatively fast and stable than HLA in half.HLA in all patients application ATG pretreatment compared with no user,the counts of CD4 + T lymphocyte subgroup trend were lower,but it was not statistical difference.This study suggests ATG for the recovery of CD4 + T lymphocyte subsets after transplantation have no obvious effect,may be associated with less number of cases.Conclusion:1 CD4+T subgroup cells recovered slowly after allo-HSCT.At 12 months after transplantation the counts still lower than normal level.The initial CD4 + T cells recovered slowest,but memory CD4 + T cells recovered relatively quickly.2 After 100 days of transplantation,Patients who have severe aGVHD,CD4+T subgroup cells were significantly lower than that in those without severe aGVHD.3 HLA in all cases with CD4 + T lymphocyte subgroup recovery is faster than the HLA half phase formed.4 The pretreatment with ATG transplant recipients,CD4 + T cell subgroup of HLA in all recovery is still faster than the HLA half phase formed. |
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