Study Of Prognostic Analysis And Treatment In Myelodysplastic Syndromes With Chromosome 7 Abnormalities

Background and ObjectivesMyelodysplastic syndromes(MDS)are a group of clonal hematopoietic stem cell disorders with a heterogeneous spectrum of ineffective hematopoiesis,refractory blood cell reduction and rapidly developing to acute myeloid leukemia(AML).Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only curable way for MDS with chromosome 7 abnormalities.Conditioning regimen is the beginning of allo-HSCT and is significant for successful allo-HSCT.Conditioning regimen is closely related to the recurrence rate after allo-HSCT and the occurrence of transplant-related complications.Therefore,it’s necessary to find a safe and effective conditioning regimen to reduce transplant-related mortality and recurrence rate,and to improve remission and disease-free survival.The ideal conditioning regimen can reduce tumor bulk,kill residual malignant tumor cells in the body,and play an immunosuppressive role to ensure implantation,reduce the post-transplant recurrence rate and transplant-related mortality,further improve the post-transplant remission rate.Decitabine(DAC)has considerable effects on hematological malignant diseases such as high-risk MDS and AML.Previous studies have shown that DAC can not only upregulate HLA-I and HLA-DR on the surface of tumor cells,increase graft-versus-leukemia(GVL)effects,but also reduce the occurrence of graft-versus-host disease(GVHD)through regulatory T cells(Tregs).Due to the definite efficacy and few adverse effects such as bone marrow suppression of DAC,it is widely used in induction or consolidation before allo-HSCT and relapse after allo-HSCT,but there are no large-scale reports on the DAC-containing conditioning regimen for MDS.Based on above knowledge,to optimize the treatment strategy,this study intends to explore the safety and effectiveness of the DAC-containing conditioning regimen and its role in MDS patients with chromosome 7 abnormalities.MethodsTo select adult MDS patients treated in the Department of Hematology,Nanfang Hospital of Southern Medical University during April 1,2009 to July 31,2019 and re-diagnosed according to the WHO 2016 diagnostic classification criteria.In this study,32 patients with monosomy 7,22 patients with del(7q)and 121 patients with normal karyotypes were included.The efficacy of HMAs or HMAs combined chemotherapy,HMAs bridging allo-HSCT,allo-HSCT in the treatment of MDS patients with monosomy 7 and del(7q)were compared.Conditioning regimen containing DAC and standard conditioning regimen were randomly used in patients underwent allo-HSCT.To evaluate the effect of HMAs and chemotherapy on patients with different karyotypes.Hematopoietic reconstruction,donor chimerism,conditioning regimen toxicity,transplant-related complications of patients treated with different conditioning regimen were observed.Results1.The median follow-up time of 175 patients was 16 months.The 3-year OS rate was 54%,and 41(23.4%)patients developed AML.The median LFS time and the 3-year LFS rate was 13 months and 67.6%,respectively.The median OS of patients with normal karyotype was significantly longer than patients with monosomy 7 and del(7q)(P<0.001).There was a significant difference in LFS between patients with monosomy 7 and patients with normal karyotype(5 months vs 16 months,P<0.05).2.The overall response rate(ORR)of 58 patients received HMAs,HMAs combined with chemotherapy or chemotherapy was 53.4%(31/58),of which 39.7%patients achieved CR,8.6%achieved PR and 5.2%HI.The ORR was 69.2%in patients with normal karyotype,20%in patients with monosomy 7,and 22%in patients with del(7q).The ORR of patients with monosomy 7 for HMAs and HMAs combined with chemotherapy was 14.3%and 33.3%,respectively.There was no significant difference in median OS between HMAs or HMAs combined with chemotherapy and supportive therapy in patients with-7/del(7q)(6 months vs 7 months,P=0.78).3.81 patients underwent allo-HSCT,including 16 patients with monosomy 7,10 patients with del(7q)and 55 patients with normal karyotype.The median OS of patients with chromosome 7 abnormalities in allo-HSCT group and non-allo-HSCT group was 14.5 months and 6 months,respectively(P<0.001).In allo-HSCT group,the median OS of patients with monosomy 7 and del(7q)was 14 months and 24.5 months,respectively(P<0.001).The median OS of patients with chromosome 7 abnormalities treated with or without HMAs before allo-HSCT was 14 months and 12 months,respectively(P>0.05).40 patients received allo-HSCT with conditioning regimen containing DAC.The 3-year OS rate of patients with monosomy 7 treated with conditioning regimen containing DAC and standard conditioning regimen was 57%and 17%,respectively(P>0.05).The 3-year OS rate of patients with del(7q)treated with conditioning regimen containing DAC and standard conditioning regimen was 83%and 50%,respectively(P>0.05).Multivariate analysis found that the conditioning regimen containing DAC was an independent favorable factor for OS(P<0.05).There were no significant differences in GVHD rate,infection rate during allo-HSCT,transplant-related mortality,and non-relapse mortality between two groups.ConclusionsMDS patients with chromosome 7 abnormalities have a low response rate to HMAs or HMAs combined with chemotherapy.HMAs bridging allo-HSCT has no prognostic impact on survival in patients with chromosome 7 abnormalities.Allo-HSCT with conditioning regimen containing DAC is a safe and effective treatment,which has improved the prognosis and survival of patients with monosomy 7.Conditioning regimen containing DAC has clinical value,and the samples need to be expanded for further research.