Study In Pharmacokinetics And Clinical Relationship About Bu Taken In Two Ways By Allo-HSCT Patients

Objective The target busulfan concentration (effective concentration) in pretreatment program is a major factor in affecting the allo-HSCT efficacy. In this study, which is domestic study for the first time, through measuring the busulfan plasma concentrationthe of hematologic malignancies patients who were treated by two ways of busulfan (oral and intravenous) in allo-HSCT preparative regimen. compare the clinical efficacy and side effects of the two groups to explore the drug exposure and clinical relationship of busulfan in different ways.Method Selecting in our hospital 19 cases of hematologic malignancies who were treated allo-HSCT from June 2006 to December 2008, put them in BU/CY2 programs preparative regimen and randomly divided them into 2 groups, 11 cases was intravenous use of Bu (intravenous group), 8 cases was oral Bu (oral group). Using Bu 7,6,5,4 days before the stem cell infusion, the total amount of intravenous Bu is 12.8㎎ / kg, every 6 hours one time and 16 times totally, 10 times diluted with normal saline, infusion centers vein, each infusion 2 hours; the total amount of oral Bu is 16㎎ / kg, every 6 hours one time and 16 times totally. Collecting all patients' blood 2ml (intravenous group 0,15,30,60,90,120,180,240,360minutes;oral group15,30,60,90,120,180,240,300,360 minutes) when the use of dose 1 and 9, centrifugal separation of plasma. Using DDTC as a derivative reagent, using pre-column derivatization HPLC method for the plasma concentrations of Bu. Using SPSS software to analyze, so as to arrive at AUC, then taking further analysis of the results of the combination.Result Intravenous group after dose 1 had an AUC of (712.97±117.51)μmol min L-1, after dose 9 has an AUC of (1041.43±183.40)μmol min L-1, the oral group after dose1 had an AUC of (909.73±146.66)μmol min L-1, after dose 9 had an AUC (1380.56±244.06)μmol min L-1, no significant difference between the two groups,;AUC of dose 9 is higher than that of dose 1,P<0.05; AUC fluctuations of oral group is large than that of intravenous group, P>0.05.the mean infusion of nuclear cell i(s7.51±2.56)×108?㎏ and(5.31±2.13)108?㎏ of two different group,P=0.078.the mean infusion CD34 positive cell is (4.17±1.70)×106?㎏ and (3.73±2.04)106?㎏ of two different group,P=0.628. All 19 patients were successfully reconstituted, both of their ANC≥0.5×109 / L median time are 12 days; intravenous group platelet≥20×109 / L median time is 15 (13 - 20) days, oral group platelet≥20×109 / L median time is 17 (14 - 46) days, platelet recovery time of intravenous group is earlier than that of the oral group,p=0.01. In intravenous group, 45.5% had liver function damage, In oral group that was 62.5%; the incidence of vomiting in intravenous and oral groups were 63.6% and 75%; the incidence of oral mucositis in intravenous group and oral group were 36.4% and 50%; there was 1 case in intravenous group had VOD, the symptoms disappeared after treatment, oral group does not appear VOD; intravenous group follow-up for 5-28 months, with a median follow-up time 12 months, seven cases survive, four cases die. Four cases of death are high-risk pre-transplant patients, two cases died at six months and one year after recurrence because of primary disease, and the other two cases who had acute lymphocyte leukemia associated with chronic GVHD died after six months and one year because of pulmonary infection. the AUC of 2 cases of recurrence respectively were 769.06μmol min L-1 and 628.76μmol min L-1 after dose 1 and 1325.09μmol min L-1 and 1302.05μmol min L-1 after dose 9.They were both in the concentration range of effective treatment, the reason why being recurrent is the original of the pathogenesis of high-risk instead of non-expose-enough; oral group 3-34 month follow-up, six cases survive, 2 cases died, 2 cases, respectively, died at 3 month and 6 month after transplantation due to sepsis and lung infection.Conclusion It is the first time report in domestic to study the busulfan plasma concentrationthe of hematologic malignancies patients who were treated by busulfan in allo-HSCT preparative regimen. There are no significant differences between oral and intravenous groups in the following aspects: pharmacokinetics, allo-HSCT and acute side effect. The pharmacokinetics parameter when patients were injected Bu 0.8mg/kg is the same with foreign conclusion. The fluctuation of AUC in intravenous group is larger than that in oral group. All in all, it is better to inject Bu in vein instead of to take orally for clinical cure. So it is safe and effective to use Myeloablative preparative regimen with a total amount of 12.8mg/kg in vein or a total amount of 16mg/kg in oral to cure hematologic malignancies.