Analysis Of Blood Concentration Monitoring And Application For Busulfan Used In Conditioning Regimen Before Autologous Stem Cell Transplantation In Multiple Myeloma

Part? Analysis of blood concentration monitoring for busulfan used in conditioning regimen before autologous stem cell transplantation in multiple myelomaObjective To analyse the individual differences in the area under the plasma concentration-time curve(AUC)of busulfan.To evaluate the correlation between hematopoietic recovery,transplant efficacy,and side effects with AUC.Methods 1?Blood samples were collected from ASCT multiple myeloma patients at specific time points namely,2h,3h,4h,6h after the first dose of busulfan-based regimen.2?The LC-MS/MS method was used to measure the blood concentration of busulfan and Calculate the AUC value of the busulfan.3?To observe the hematopoietic recovery,transplantation efficacy and side effectsof patients.Results 1?The range of AUC(0-t)and AUC(0-?)in 11 patients with MM were 690.61-1049.91?mol·min·L-1 and 917.15-1386.08?mol·min·L-1,the CV%were 13.17% and 12.28% respectively.2 ? All the MM patients were successfully hematopoietic reconstruction,the median time to neutrophil engraftment were 9(8-10)d,the median time to platelet engraftment were 10(9-14)d.3?All patients did not experience discontinuation of treatment due to severe regimen-related adverse events.Adverse reactions to gastrointestinal tract and liver damage are associated with higher incidence among regimen-related adverse events.4?All the MM patients achieved s CR,CR or VGPR after autologous transplantation.The SCR/CR rates after ASCT(81.82%)were higher than that before it(45.45%)(P > 0.05).5 ? According to the AUC optimal treatment used in foreign countries,there was no definite correlation between AUC and clinical efficacy in this study.Conclusions 1?The CV% in AUC values do exist.Tt is necessary to carry out busulfan blood concentration monitoring.2?The best therapeutic window of busulfan-AUC for foreign patients may not be suitable for domestic patients.3?Large clinical trials should be carried out to study the best therapeutic window of busulfan-AUC for domestic patients.Part? Application of the conditioning regimen with busulfan and cyclophosphamide in autologous stem cell transplantation in multiple myelomaObjective Evaluate the safety and efficacy of BUCY(busulfan and cyclophosphamide)conditioning regimen for autologous hematopoietic stem cell transplantation(ASCT)in patients with multiple myeloma(MM).Methods We retrospectively analyzed the clinical data of 72 MM patients who received transplantation in the Hematology Department of the First People's Hospital of Soochow University from May 2012 to June 2015.Among them,36 patients underwent BUCY regimen while the others received high dose melphalan.Those were compared between the two groups including the complication,the hematopoietic reconstitution and the post-transplantation efficacy.Results There were no significant differences in age,stage,induction therapy,mobilization method between the two groups.The transplantation-related adverse events were similar in both groups but the incidence of pulmonary infection and bloodstream infection were slightly higher in BUCY group.The median time to neutrophil engraftment in the BUCY and HDM groups were 10(8-17)days versus 10(9-13)days,taking the same time on average(P=0.046).On the other hand,the median time to platelet engraftment was10(8-18)versus 11(9-47)days accordingly(P=0.017).The TRM in both group was2.7%.The SCR/CR rates after ASCT(47.2% and 50.0%)were higher than those before it(38.9% and 26.6%),in both groups.In the BUCY group,the median follow-up was25.5(0-39)months.14 patients(38.9%)underwent disease progression.The 3-year progression-free survival(PFS)rate was 40%.Correspondingly,in the HDM group,the median follow-up time was33.5(0-54)months.23 patients(63.9%)developed disease progression and the 3-year PFS rate was 41%.The median progression-free survival is 30 months in BUCY group and 28 months in HDM group(P=0.326).Conclusions The BUCY regimen is a safe and effective therapy for ASCT in patients with multiple myeloma.Besides,BUCY regimen is not inferior to HDM regimen.In conclusion,BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in multiple myeloma.