Clinical Efficacy And Safety Analysis Of Modified Donor Lymphocyte Infusion In The Treatment Of Malignant Hematologic Diseases

Objective:To study the clinical efficacy and safety of modified donor lymphocyte infusion(MDLI)in the treatment of middle-risk and high-risk hematologic malignancies(HMs)without allogeneic hematopoietic stem cell transplantation(Allo-HSCT).Methods:A retrospective study was conducted on the case data of 16 patients who received MDLI hematologic malignancies in the Second Hospital of Shanxi Medical University from May 2014 to August 2018.All 16 patients started adoptive cell immunotherapy with MDLI after completing standard dose chemotherapy.The primary outcome measures were CR rate,hematopoietic reconstruction time,incidence of acute and chronic GVHD,minimal residual disease(MRD)status,overall survival(OS)and progression-free survival(PFS)after MDLI.Acute and chronic graft-versus-host disease(GVHD)is diagnosed and graded according to the Seattle criteria.No patients were lost to follow-up,and follow-up included hospital visits,phone calls,and letters.Univariate analysis was performed for gender,age,disease type,gene mutation,risk stratification,pretreatment,disease status before cell transfusion,number of mononuclear cells(MNC),number of CD34+cells,MRD status after infusion,and remission of bone marrow after cell therapy.To explore the non-genetic factors affecting the prognosis of patients with middle and high risk hematologic malignancies,and to monitor the occurrence of adverse reactions in all patients receiving treatment.Results:(1)A total of 35 donor lymphocyte transfusations were completed in 16 patients,and the CR rate was 43.75%and the overall response rate(ORR)was 87.5%after MDLI.(2)Median values of MNC and CD34+were 2.7(1.6-3.76)×10~8/Kg and 2.1(1.3-4.7)×10~6/Kg,respectively.The incidence of a GVHD was 28.6%,and the a GVHD after treatment was no more thanⅡgrade.c GVHD was not found in all patients.(3)After MDLI infusion in 16 patients,MRD was negative in 10 patients,persistent negative in 7 patients,and molecular recurrence in 3 patients after 1 month,3 months and 4months,respectively.One patient had negative MRD after reinfusion of MDLI and has survived to this day.Two patients deteriorated,refused reinfusions and died.MRD was positive in 6 patients,MDLI reinfusion in 3 patients,and MRD was negative in 2 patients.The 3-year OS of the MRD negative group after MDLI was significantly higher than that of the MRD positive group(P<0.05).(4)The follow-up time ranged from 1 to 71.8 months,with a mean observation time of 28.2 months and a median survival time of 21.6 months.The 3-year survival rate was58.3%and the 3-year progression-free survival rate was 50%with MDLI cell therapy.Of the 16 patients,9 patients survived,and of the 7 patients died,4 patients(25%)died of the recurrence of the original disease,and 3 patients died of infection.(5)The results showed that the high-dose pretreatment regimen(P=0.020),ORR after cell therapy(P=0.048),and MRD negative after infusion(P=0.036)could significantly prolong OS and PFS.Conclusion:(1)MDLI has certain effects in the treatment of middle-risk and high-risk hematologic malignancies.(2)There were no obvious toxic and side effects of middle-risk and high-risk hematologic malignancies in MDLI treatment,and there were no treatment-related deaths.(3)Dynamic review of MRD changes after MDLI can prevent early recurrence after MDLI diagnosis.(4)High-dose preconditioning regimens,ORR after cell therapy,and MRD negative after infusion significantly prolonged OS and PFS.(5)Multicenter and large-sample clinical studies are still needed to determine whether MDLI treatment can prolong the survival of middle-risk and high-risk hematologic malignancies.