| Part ? Analysis of distribution and risk factors of anti-HLA antibody positive in patients with myelodysplastic syndromeObjective:The positive distribution of HLA antibody and the risk factors of HLA antibody were analyzed in myelodysplastic syndrome(MDS)patients,so as to improve the prognosis of transplantation in MDS patients.METHODS:Retrospective analysis of 180 patients with MDS admitted to the First Affiliated Hospital of Soochow University from January 1,2016 to December 29,2018,through patients with bone marrow morphology,immunology,cytogenetics,and molecular biology(MICM)Data to identify patients with disease diagnosis and disease classification according to the 2016 WHO guidelines.The anti-HLA antibody screening test was performed using Luminex technology,and the MFI value?1000 established in the laboratory was used as a criterion for judging antibody positive.Risk factors for positive anti-HLA antibody in MDS were analyzed by logistic regression model.Results:Of the 180 patients with MDS,60(33.3%)were anti-HLA-positive and 120(66.7%)were negative.Of the 180 patients,23 were anti-HLA-I-positive(12.8).%),10 patients(5.5%)with positive anti-HLA-II antibody and 27 patients(15.0%)with positive anti-HLA-I and II antibodies.Among 66 female patients,34(51.5%)were positive for anti-HLA antibody,and 10(71.4%)were positive for anti-HLA antibody in 14 patients with high risk of IPSS prognosis.Multivariate analysis of anti-HLA antibody positive in 180 patients with MDS showed the following:(1)female with prior pregnancy(P=0.001,OR=6.043,95%CI 2.001-18.252),prior transfusions(P=0.006,OR=5.149,95%CI 1.616-16.411),duration?2.0 months(P=0.024,ORF=2.910,95%CI 1.147-7.380),IPSS high-risk group(P=0.013,OR=8.224,95%CI 1.549-43.647)was a risk factor for anti-HLA antibody positive.(2)female with prior pregnancy(P=0.001,OR=22.824,95%CI 3.727-139.766),prior transfusions(P=0.032,OR=9.830,95%CI 1.212-79.717),duration>2.0 months(P=0.015,OR=8.250,95%CI 1.516-44.882),IPSS high-risk group(P=0.010,OR=50.901,95%CI 2.557-1013.099)were risk factors for anti-HLA-?+? antibody positive.(3)female with prior pregnancy?2 were independent risk factors for anti-HLA-? antibody positive(P=0.015,OR=4.859,95%CI 1.353-17.444).(4)IPSS high-risk group was an independent risk factor for anti-HLA-? antibody positive(P=0.044,OR=27.613,95%CI 1.099-693.737).(5)As the number of pregnancies increases,the risk of anti-HLA antibody positive increases.Conclusions:The positive rate of anti-HLA antibody in patients with MDS was about 33.3%.The positive rate of anti-HLA antibody was higher in female patients and patients with high risk of IPSS prognosis.the IPSS high-risk patients,patients with disease duration? 2.0 months,prior transfusions and female with prior pregnancy were risk factors for anti-HLA antibody positive.Part ? Effect of anti-HLA antibody on the prognosis of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndromeObjective:To analyze the correlation between anti-HLA antibody and acute graft-versus-host disease,recurrence and survival after allo-HSCT in MDS patients,so as to guide clinical assessment of graft prognosis well.METHODS:A retrospective analysis of 107 patients with MDS who underwent all-HSCT at the First Affiliated Hospital of Suzhou University from January 1,2016 to December 29,2018.Of the 107 patients enrolled,25 were allogeneic hematopoietic stem cell transplantation,16 were unrelated hematopoietic stem cell transplantation,and 66 were haploid hematopoietic stem cell transplantation.All patients had completed anti-HLA antibody screening test and HLA high-resolution genotyping for patients before transplantation.Dynamic detection of specific antibodies was performed in some patients before and after transplantation,and HLA high-resolution gene typing was confirmed in patients.The effects of anti-HLA antibodies on the prognosis of transplantation were analyzed in combination with post-transplant related indicators.Results:Of the 107 patients with MDS(including conversion to AML),37(34.6%)were pre-existing anti-HLA antibody-positive patients and 70(65.4%)were negative.Of the anti-HLA antibody-positive patients,13(35.1%)were positive for HLA-I antibodies,8(21.6%)were positive for HLA-II antibodies,and 16(43.3%)were class I and class II antibodies are positive.The proportion of female patients in the antibody-positive group was higher than that in the antibody-negative group(56.8%vs.35.7%,P=0.037),and the prior pregnancy number of female in the antibody-positive group was higher than that in the negative(51.4%vs.26.1%,P=0.034),the difference is statistically significant.The proportion of patients with antibody disease diagnosis type MDS-EB2 was higher than that without antibody(56.8%vs.27.1%,P=0.014),and the difference was statistically significant.In the pre-existing anti-HLA antibody-positive group and the negative group,the median time of granulocyte hematopoietic reconstitution was 12(10-20)days,12(9-19)days,and there was no statistical difference(P=0.216);The median time of the megakaryocyte hematopoietic reconstruction were 15(9-104)days and 14(9-30)days respectively in the anti-HLA antibody positive and and the negative,there was no statistical difference(P=0.209).In the group of megakaryotic reconstruction time?28days,the patients with negative preexisting HLA antibodies were 4.4%(3/68)and the median time was 29(29-30)days,the patients with positive anti-HLA were 13.9%(5/36)and the median time was 68(29-104)days,with a difference but no statistical significance(P=0.093).There was no statistical difference in grade ?-? aGVHD(42%vs.35.6%,P=0.498),recurrence rate(14.3%vs.6,5%,P=0.757),TRM(9.7%vs.14.3%,P=0.982),between pre-existing anti-HLA antibody-positive group and the negative group.There was no statistically difference in ?-? aGVHD cumulative incidence between pre-existing anti HLA-? positive and negative group(P=0.593),also in anti HLA-? positive group(P=0.273)and anti HLA-?+? positive group(P=0.998).The 2-year probability of OS for the pre-existing anti-HLA antibody positive group and the negative were 77.6%and 83.6%(P=0.823).The 2-year probability of DFS for pre-existing anti-HLA antibody positive and negative groups were 67.4%and 79.6%(P=0.888).The 2-year probability of OS pre-existing anti-HLA antibody was strongly positive,and the positive group were 69.9%and 66.1%,respectively,which was lower than the negative group(83.6%),but there was no statistical significance(P=0.958).Pre-existing anti-HLA-? antibody-positive,anti-HLA-? antibody-positive,antibody-class? and class ? antibodies were positive,and the 2-year probability of OS after transplantation was 92.3%,85.7%,and 59.2%,respectively,but no statistically differences(P=0.808).There was no statistically difference between pre-existing anti-HLA-?antibody-positive and the negative group(P=0.748),also in anti HLA-? positive group(P=0.866)and anti HLA-?+? positive group(P = 0.375).Of the 107 patients enrolled,41 patients who received HLA-matched hematopoietic stem cell transplantation had a 2-year OS of 83.5%,and 66 patients who received a haploid hematopoietic stem cell transplant had a 2-year OS of 77.1%(P=0.575).The 2-year probability of OS was 90.1%in 69 patients without ?-? aGVHD after transplantation,and the 2-year probability of OS in 35 patients with ?-? aGVHD was 64.4%(P=0.157).Except for univariate analysis other than anti-HLA antibodies,patients with ?-? degree aGVHD had an increased risk of TRM after transplantation(P=0.04,HR=3.633,95%CI 1.060-12.449).Among the 27 patients with antibody results before and after transplantation,the 2-year OS of patients in the continuously positive group was 70%,and the continuously negative group and the antibody titer decreased group was 100%,with statistically significant difference(P=0.016).There was a statistically significant difference in OS between the continuously positive group and the negative(P=0.037).The 2-year DFS of the continuous negative group,the continuous positive group and the antibody titer decreased group were respectively 90%,60%and 100%,,with statistically difference(P=0.030).There was no significant difference in DFS between the continuously positive group and the negative(P=0.083).Conclusions:in patients with MDS,pre-existing anti-HLA antibodies may be one of the factors affecting the poor prognosis of allo-HSCT.OS and DFS of patients with continuous positive anti-HLA antibodies are reduced after transplantation.Therefore,it is particularly important to detect anti-HLA antibodies before transplantation and to detect antibody levels after transplantation. |
PDF Full Text Request