Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia
<p>Abstract</p> <p>Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2010-10-01
|
Series: | Journal of Hematology & Oncology |
Online Access: | http://www.jhoonline.org/content/3/1/36 |
id |
doaj-998d06ee2d9a452db5ef3f47519f5f69 |
---|---|
record_format |
Article |
spelling |
doaj-998d06ee2d9a452db5ef3f47519f5f692020-11-24T21:00:31ZengBMCJournal of Hematology & Oncology1756-87222010-10-01313610.1186/1756-8722-3-36Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemiaNishihori TaigaKharfan-Dabaja Mohamed AAnasetti ClaudioKim JongphilPidala JosephField TeresaPerkins JanellePerez LiaFernandez Hugo F<p>Abstract</p> <p>Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days) and cyclophosphamide (60 mg/kg IV × 2 days) - (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000 μM/L*min per day × 4 days) and fludarabine (40 mg/m2 × 4 days) - (t-IV Bu/Flu). The Bu/Cy and t-IV Bu/Flu groups significantly differed according to donor relation, stem cell source, aGVHD prophylaxis, remission status, primary vs. secondary disease, median age, and % blasts prior to HCT (p < 0.01 for each). Conditioning with t-IV Bu/Flu reduced early toxicity including idiopathic pneumonia syndrome (IPS) and hepatic veno-occlusive disease (VOD). Additionally, the trajectory of early NRM (100 day: 16% vs. 3%, and1 year: 25% vs. 15% for Bu/Cy and t-IV Bu/Flu, respectively) favored t-IV Bu/Flu. Grade II-IV aGVHD (48% vs. 82%, p < 0.0001), as well as moderate/severe cGVHD (7% vs. 40%, p < 0.0001) differed between the Bu/Cy and t-IV Bu/Flu groups, due to the predominance of peripheral blood stem cells in the t-IV Bu/Flu group. Pharmacokinetic targeting of intravenous busulfan in combination with fludarabine is associated with reduced conditioning regimen related toxicity compared to oral busulfan and cyclophosphamide. However, multivariable analysis did not demonstrate significant differences in overall survival (p = 0.78) or non-relapse mortality (p = 0.6) according to conditioning regimen delivered.</p> http://www.jhoonline.org/content/3/1/36 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nishihori Taiga Kharfan-Dabaja Mohamed A Anasetti Claudio Kim Jongphil Pidala Joseph Field Teresa Perkins Janelle Perez Lia Fernandez Hugo F |
spellingShingle |
Nishihori Taiga Kharfan-Dabaja Mohamed A Anasetti Claudio Kim Jongphil Pidala Joseph Field Teresa Perkins Janelle Perez Lia Fernandez Hugo F Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia Journal of Hematology & Oncology |
author_facet |
Nishihori Taiga Kharfan-Dabaja Mohamed A Anasetti Claudio Kim Jongphil Pidala Joseph Field Teresa Perkins Janelle Perez Lia Fernandez Hugo F |
author_sort |
Nishihori Taiga |
title |
Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia |
title_short |
Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia |
title_full |
Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia |
title_fullStr |
Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia |
title_full_unstemmed |
Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia |
title_sort |
pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia |
publisher |
BMC |
series |
Journal of Hematology & Oncology |
issn |
1756-8722 |
publishDate |
2010-10-01 |
description |
<p>Abstract</p> <p>Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days) and cyclophosphamide (60 mg/kg IV × 2 days) - (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000 μM/L*min per day × 4 days) and fludarabine (40 mg/m2 × 4 days) - (t-IV Bu/Flu). The Bu/Cy and t-IV Bu/Flu groups significantly differed according to donor relation, stem cell source, aGVHD prophylaxis, remission status, primary vs. secondary disease, median age, and % blasts prior to HCT (p < 0.01 for each). Conditioning with t-IV Bu/Flu reduced early toxicity including idiopathic pneumonia syndrome (IPS) and hepatic veno-occlusive disease (VOD). Additionally, the trajectory of early NRM (100 day: 16% vs. 3%, and1 year: 25% vs. 15% for Bu/Cy and t-IV Bu/Flu, respectively) favored t-IV Bu/Flu. Grade II-IV aGVHD (48% vs. 82%, p < 0.0001), as well as moderate/severe cGVHD (7% vs. 40%, p < 0.0001) differed between the Bu/Cy and t-IV Bu/Flu groups, due to the predominance of peripheral blood stem cells in the t-IV Bu/Flu group. Pharmacokinetic targeting of intravenous busulfan in combination with fludarabine is associated with reduced conditioning regimen related toxicity compared to oral busulfan and cyclophosphamide. However, multivariable analysis did not demonstrate significant differences in overall survival (p = 0.78) or non-relapse mortality (p = 0.6) according to conditioning regimen delivered.</p> |
url |
http://www.jhoonline.org/content/3/1/36 |
work_keys_str_mv |
AT nishihoritaiga pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT kharfandabajamohameda pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT anasetticlaudio pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT kimjongphil pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT pidalajoseph pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT fieldteresa pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT perkinsjanelle pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT perezlia pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia AT fernandezhugof pharmacokinetictargetingofintravenousbusulfanreducesconditioningregimenrelatedtoxicityfollowingallogeneichematopoieticcelltransplantationforacutemyelogenousleukemia |
_version_ |
1716779544738791424 |