CLGAB Preconditioning Regimen For Autologous Stem-cell Transplantation In Lymphomas

Background:Lymphoma,as the most common malignant tumor in the blood system,ranks 10th in mortality among malignant tumors in China,with a 5-year survival rate of only 37.2%.In particular,high-risk aggressive,relapsed/refractory lymphomas have a poor prognosis with treatment.For patients with high-risk aggressive,relapsed/refractory lymphoma,autologous hematopoietic stem cell transplantation（ASCT）has been recommended for first-line consolidation therapy and post-relapse salvage therapy in both domestic and international guidelines and consensus,boasting significant prolongation of the survival of patients.The conditioning regimen is the key to the curative effect of ASCT.All the classical and commonly used clinical ASCT regimens for lymphoma need to be further improved.However,no clear optimal solution has been conceived so far.Basic and clinical studies have proved that the combination of Cladribine,Gemcitabine and Busulfan has an obvious synergistic killing effect on lymphoma cells,which are safe and effective for the conditioning of lymphoma ASCT.Cytarabine also shows favourable anti-lymphoma activity in anti-lymphoma,and has a significant synergistic effect with Cladribine.For this reason,a novel conditioning regimen of CLGAB was combined in our center for related research of lymphoma ASCT,so as to explore a better conditioning regimen.Objective:To evaluate the efficacy and safety of CLGAB conditioning regimen in lymphoma ASCT,in order to explore a safe and efficient conditioning regimen for patients with lymphoma.Methods:All subjects in this study were those with lymphoma who underwent ASCT with CLGAB regimen or BEAM/Be EAM/SEAM regimen in the Department of Hematology of Henan Provincial People’s Hospital from January 2020 to December 2021.Be EAM and SEAM are collectively referred to as BEAM-Like（BEAM-L）regimen together with BEAM.CLGAB regimen was the experimental group,beam-L regimen was the control group.All patients were divided into CLGAB group and BEAM-L group according to inclusion and exclusion criteria,and all signed informed consent to conduct a prospective,open-label clinical trial.The conditioning regimen was as follows:CLGAB regimen:Cladribine 5mg/m²·d^-1qd-6d～-2d,Gemcitabine 1250mg/m²·d^-1qd-6d,Cytarabine 1.5g/m²q12h-5d～-4d,Busulfan 0.8mg/kg q6h-5d～-2d;BEAM regimen:Camustine 300mg/m²qd-7d,Etoposide 100mg/m²q12h-6d～-3d,Cytarabine 200mg/m²q12h-6d～-3d,Mepharon 140mg/m²qd-2d;Be EAM regimen:Camustine in BEAM regimen was replaced by Bendamustine,while other drugs remained unchanged.SEAM regimen:Camustine in BEAM regimen was replaced by Semustine,while other drugs remained unchanged.After transplantation,the patients were followed up periodically,and some of them were treated with Lenalidomide or Chidamide and other drugs as maintenance therapy according to their condition and wishes.The basic clinical features of the two groups were collected and analyzed.The number of stem cells collected,the myeloablative effect of conditioning,adverse reactions of conditioning,hematopoietic reconstruction,disease remission after transplantation and the survival of patients were statistically compared between the two groups,and the safety and curative effect of CLGA scheme were analyzed and discussed.All patients were followed up until March 15th,2022.Results:1.A total of 34 patients with lymphoma who underwent ASCT were enrolled,including 15 patients in CLGAB group and 19 patients in BEAM-L group.In BEAM-L group,there were 3 patients receiving BEAM Mregimen,7 patients receiving Be EAM regimen,and 9 patients receiving SEAM regimen.No statistically significant differences were observed in basic clinical features between CLGAB group and BEAB-L group.In terms of stem cell collection,the mean values of MNC collected in CLGAB group and BEAM-L group were 11.03±3.64×10⁸/Kg and 9.72±3.90×10⁸/Kg,respectively,and the median values of CD34+collected were 16.68（3.48,80）×10⁶/Kg and 11.82（2.66,86）×10⁶/Kg,respectively,with no statistical significance（P=0.82,P=0.57）.2.The adverse reactions of conditioning in the two groups were mainly nausea/vomiting,fever,oral mucositis,diarrhea,etc.,and most of them were grade I/II.After symptomatic and supportive treatment,they were all improved and controllable.No liver VOD and TRM occurred in the two groups,and there was no significant difference in the incidence of overall adverse reactions and grade III/IV adverse reactions between the two groups,All P values were>0.05.3.Myeloablative effect and hematopoietic co-construction:The time of grade IV bone marrow transplantation in CLGAB group was faster than that in BEAM-L group,with median time of+1d（-2,+4d）and+2d（-3,+5d）,respectively,P=0.033.There was no significant difference between the two groups in the minimum value of platelets,the duration of agranulocytosis,the number of days of G-CSF application,the number of platelets infused,and the number of red blood cells infused（P values were 0.925,0.930,0.187,0.490 and 0.748,respectively）,but CLGABgroup had fewer average number of days of TPO application during transplantation（7.40±2.67vs.11.63±4.04,P=0.001）.All patients succeeded in hematopoietic co-construction.The hematopoietic reconstruction time in CLGAB group was shorter than that in BEAB-L group.The median time of neutrophils implantation in CLGAMgroup and BEAM-L group was 9d（7,10 d）and 10d（8,13 d）,and the median time of PLT implantation was 9d（7,12d）and 12d（8,18d）,respectively,with statistically significant difference.（P=0.043,P=0.006）.4.The evaluation after 3 months of transplantation showed that the early ORR of CLGAB group and BEAM-L group were 100%and 84.2%respectively（P=0.238）.15.The median follow-up time of CLGAB group was 13.0（3,27）months.All 15 patients survived without recurrence or progression,with both OS and PFS rates of 100%.In BEAM-L group,the median follow-up time was 11.5（3,27）months.Three patients relapsed,and one patient died 5 months after transplantation due to disease progression,with OS and PFS rates of 94.7%and 84.2%,respectively.There was no significant difference in PFS and OS between the two groups（P=0.114,P=0.378）.Conclusion:1.CLGAB conditioning regimen is safe and tolerable in the application of lymphoma ASCT,without increasing the incidence of adverse reactions;2.CLGAB regimen has an ideal myeloablative effect and faster hematopoietic reconstruction;3.Early ORR of CLGAB were 100%,up o the last follow-up time,the OS and PFS rates of CLGAB regimen were 100%,showing a favourable potential for disease remission,which is expected to prolong the long-term survival time of patients;4.CLGAB conditioning regimen is feasible and effective,which is worthy of further study.However,long-term follow-up results of more samples are still needed for specific conclusions.