Efficacy Analysis Of Allogeneic Hematopoietic Stem Cell Transplantation With Cladribine Intensive Conditioning Regimen In The Treatment Of High-risk Acute Myeloid Leukemia

Objective:Firstly,to explore the efficacy and safety of intensive conditioning regimen with cladribine in the treatment of high-risk acute myeloid leukemia(AML).Secondly,to explore the clinical prognosis of intensive conditioning regimen with cladribine in the treatment of high-risk AML.Thirdly,to explore the cumulative incidence of relapse and non-relapse mortality of intensive conditioning regimen with cladribine in the treatment of high-risk AML.Methods:The clinical data of 28 high-risk AML patients who received cladribine combined with busulfan(Bu)and cyclophosphamide(Cy)(BuCy)before allogeneic hematopoietic stem cell transplantation in Zhujiang Hospital of Southern Medical University from October 2016 to June 2020 were analyzed retrospectively.Regimen related toxicity(RRT),cumulative overall survival rate(OS),cumulative progression-free survival rate(PFS),relapse rate,NRM and prognostic risk factors were analyzed.Results:Firstly,the granulocytic system of 28 patients were implanted successfully,and the median time of implantation was 13.5(9-20)days.One patient failed to implant megakaryocytes,with a failure rate of 3.6%,and a median time of 15(10-23)days.RRT mostly occurred within 2 weeks of pretreatment.The incidence of grade Ⅰ/Ⅱ RRT was 39.3%(11 hands 28).No patient developed grade Ⅲ/Ⅳ RRT.AGVHD occurred in 9 patients(32.1%)within 100 days after transplantation/DLI.Of the 25 assessable patients,6(21.4%)developed cGVHD.Sixteen patients(57.1%)developed post-transplant infection,mainly in the respiratory tract and urinary tract.Secondly,the median follow-up time was 12.33months(95%CI8.24-16.42months).5 cases died after transplantation,of which 2 cases died of relapse and 3 cases died of transplantation-related complications,including 2 cases of aGVHD and 1 case of respiratory tract infection.Three of the 28 patients relapsed.The expected 6-month and 1-year cumulative OS were 85.7±6.6%and 81.6±7.5%,respectively,and the expected 6-month and 1-year cumulative PFS were 85.7±6.6%and 82.0 ±7.3%,respectively.The OS of the patients with pre-transplantation relapse,positive MRD before transplantation,BM+PB transplantation and aGVHD were significantly lower than those in the control group.The PFS of the patients with pre-transplantation relapse,BM+PB transplantation and aGVHD were significantly lower than those in the control group.Multivariate analysis showed that pre-transplantation relapse was an independent poor prognostic factor for OS and PFS.The 1-year cumulative relapse rate and cumulative non-relapse mortality rate were 7.3%and 10.7%,respectively.The risk of the patients with pre-transplantation relapse and aGVHD were higher than those in the control group.The risk of non-relapse mortality after BM+PB transplantation was higher than that in the control group.Conclusion:The intensified conditioning regimen of cladribine combined with BuCy used in this study reduced the relapse rate of patients with high-risk AML after transplantation,and was of limited regimen related toxicity,satisfactory safety,low implantation failure rate and good recovery of hematopoietic reconstruction.This intensified conditioning regimen did not increase the incidence of GVHD,and was of low incidence of severe infections and non-recurring mortality.This study found that pre-transplantation relapse was an independent adverse prognostic factor affecting OS and PFS,and the relapse risk of and pre-transplantation relapse and aGVHD after transplantation was higher than that of the control group.In summary,for high-risk AML patients,the intensified pretreatment regimen of cladribine combined with BUCY can improve the prognosis of patients and has certain clinical application value.