scholarly journals 300: Once Daily Busulfan Cyclophosphamide is Well Tolerated and Effective Prior to Allogeneic Hematopoietic Stem Cell Transplantation

2008 ◽  
Vol 14 (2) ◽  
pp. 111
Author(s):  
J. LeMaistre ◽  
C. Bachier ◽  
B. Smith ◽  
C.F. LeMaistre ◽  
P.J. Shaughnessy
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Once Daily

Once Daily Busulfan Cyclophosphamide Is Well Tolerated and Effective Prior to Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1996-1996
Author(s):  
Julia A. LeMaistre ◽  
Carlos Bachier ◽  
Brad Smith ◽  
C.F. LeMaistre ◽  
Paul J. Shaughnessy
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Once Daily ◽  
Allogeneic Hct ◽  
One Year

Abstract The development of intravenous busulfan (Bu) allowed for the delivery of a standard daily dose of Bu to be given in one dose instead of dividing 4 times per day. Pharmacokinetic (PK) studies of Bu support the feasibility of once daily dosing and prior clinical studies found no unexpected toxicity of once daily Bu when combined with fludarabine. Based on this data we began an institutional protocol of delivering Bu once daily follwed by standard cyclophosphamide (Cy) and allogeneic hematopoietic stem cell transplantation (HCT). Only limited data in the literature describes toxicity and clinical outcomes of once daily BuCy. We report a retrospective review of our institutional data using once daily BuCy vs 4x daily BuCy and total body irradiation (TBI)/Cy in pts who received allogeneic HCT from January 2000 to December 2006. Bu 3.2mg/kg daily × 4 days followed by Cy 60mg/kg daily × 2 days was given to 42 patients (pts). Bu 0.8mg/kg/dose given 4x daily for 4 days followed by Cy 60mg/kg was given to 15 pts. Cy 60mg/kg daily for 2 days and fractionated TBI 1200 cGy delivered over 3 days was given to 60 pts. All donors were HLA matched at A, B, C, DR, and DQ and were related/unrelated in 23/19, 11/4, and 21/39 in the once daily BuCy, 4x daily BuCy, and TBI/Cy, respectively. Significantly more pts with myeloid leukemias received a BuCy regimen and significantly more pts with lymphoid malignancies received TBI/Cy. Median follow up for all pts was 370 days. VOD developed in 2 pts in the once daily BuCy group, 1 pt in the 4x daily BuCy group, and in no pts in the TBI/Cy group. Acute GVHD grade II-IV occured in 33% of the once daily BuCy pts, 53% of the 4x daily BuCy pts, and 32% of the TBI/Cy pts. Estimated actuarial transplant related mortality (TRM) and survival are described in the table below. There was no statistical difference in TRM or survival between the once daily and 4x daily BuCy groups or the total BuCy group and TBI/Cy group. The once daily BuCy group had significantly less TRM than the TBI/Cy group at 100 days (p=0.04) and at 1 year (p=0.01). The once daily BuCy group also had significantly better survival at one year compared to the TBI/Cy group (p=0.01), but this became non-significant at 3 years. The significant differences in the pt populations treated in the BuCy and TBI/Cy groups, as well as the retrospective nature of this study, limit the ability to draw conclusions comparing the groups. However, this review does demonstrate once daily BuCy and allogeneic HCT is well tolerated with no unexpected TRM, and provides good long term survival in pts with myeloid malignancies. Survival and TRM 1xBuCy (95%CI) 4xBuCy (95%CI) Cy/TBI (95%CI) 100 day TRM 7% (1–16%) 21% (7–51) 22% (15–35) 1 year TRM 21% (11–38) 37% (17–69) 45% (33–59) 1 year Survival 70% (53–82) 47% (21–69) 49% (35–61) 3 year Survival 43% (24–59) 27% (8–50) 37% (24–49)

Favorable Outcome Of Hematopoietic Stem Cell Transplantation Using a Targeted Once-Daily IV Busulfan Fludarabine Etoposide Regimen In Pediatric and Infant ALL Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4553-4553
Author(s):  
Hyoung Jin Kang ◽  
Ji Won Lee ◽  
Sung jin Kim ◽  
Seung Hwan Lee ◽  
Kyung-Sang Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Favorable Outcome ◽  
Hematopoietic Stem ◽  
Once Daily

Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae such as growth impairment, endocrinologic and metabolic problem, and secondary malignancies. Busulfan based conditioning regimen with cyclophosphamide has been used as an alternative to TBI based regimen in many diseases including pediatric ALL. Etoposide has been widely used in hematopoietic stem cell transplantation (HSCT) for lymphoid and myeloid malignancy because of its anti-leukemic effect, and a conditioning regimen containing busulfan, cyclophosphamide and etoposide (BuCyVP) was used in many studies including pediatric patients. But, toxicities have been reported in some studies using BuCyVP regimen. Recently, a reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising results. Also, therapeutic drug monitoring (TDM) and administration of targeted dose of busulfan has been recommended to improve the outcome of HSCT. In this study, we evaluated the outcome of HSCT using a targeted once-daily intravenous (IV) busulfan fludarabine etoposide (BuFluVP) regimen in pediatric and infant ALL. The conditioning regimen was composed of busulfan, fludarabine (40 mg/m2 once daily i.v. on days -8 ∼ -3) and etoposide (20 mg/kg once daily i.v. on days -4 ∼ -2). Busulfan (≥ 1 year-120 mg/m2 and < 1 year-80 mg/m2) was administered once daily as the first dose on day -8, and targeted dose of busulfan was used according to the TDM results on day -7 ∼ -5. A total of 33 patients were evaluated. Donor-type neutrophil engraftment was achieved in all patients. Veno-occlusive disease occurred in 5 (15.2%) patients, but all of them were successfully treated. Grade II-IV acute GVHD developed in 11 patients (grade 2 in 9 patients, grade 3 in 1 and grade 4 in 1 patient) and the cumulative incidence was 33.6%. Chronic GVHD developed in 3 patients (2 extensive and 1 limited). Three patients died of treatment-related mortality (TRM) and the cumulative incidence was 9.1%. The causes of TRM were adenoviral pneumonia in 1, respiratory syncytial viral (RSV) pneumonia in 1 and interstitial lung disease in 1 patient. Relapse occurred in 3 patients and cumulative incidence was 9.1%. Overall survival (OS) and event free survival (EFS) of all patients were 84.9% and 81.8%, respectively. EFS showed no difference according to the type of HSCT (77.8% in related BMT/PBSCT, 82.4% in unrelated BMT/PBSCT, and 85.7% in CBT, P=0.95). Eleven patients (33.3%) were infants at diagnosis, and OS of these patients was 81.8%. Our study demonstrated that HSCT using a targeted once-daily IV BuFluVP regimen showed favorable outcome and could be one option for HSCT in pediatric and infant ALL. Disclosures: No relevant conflicts of interest to declare.

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