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Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia.
J Hematol Oncol. 2010 Oct 06; 3:36.JH

Abstract

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.

Authors+Show Affiliations

Department of Blood and Marrow Transplantation, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. joseph.pidala@moffitt.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20925957

Citation

Pidala, Joseph, et al. "Pharmacokinetic Targeting of Intravenous Busulfan Reduces Conditioning Regimen Related Toxicity Following Allogeneic Hematopoietic Cell Transplantation for Acute Myelogenous Leukemia." Journal of Hematology & Oncology, vol. 3, 2010, p. 36.
Pidala J, Kim J, Anasetti C, et al. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. J Hematol Oncol. 2010;3:36.
Pidala, J., Kim, J., Anasetti, C., Kharfan-Dabaja, M. A., Nishihori, T., Field, T., Perkins, J., Perez, L., & Fernandez, H. F. (2010). Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. Journal of Hematology & Oncology, 3, 36. https://doi.org/10.1186/1756-8722-3-36
Pidala J, et al. Pharmacokinetic Targeting of Intravenous Busulfan Reduces Conditioning Regimen Related Toxicity Following Allogeneic Hematopoietic Cell Transplantation for Acute Myelogenous Leukemia. J Hematol Oncol. 2010 Oct 6;3:36. PubMed PMID: 20925957.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. AU - Pidala,Joseph, AU - Kim,Jongphil, AU - Anasetti,Claudio, AU - Kharfan-Dabaja,Mohamed A, AU - Nishihori,Taiga, AU - Field,Teresa, AU - Perkins,Janelle, AU - Perez,Lia, AU - Fernandez,Hugo F, Y1 - 2010/10/06/ PY - 2010/09/13/received PY - 2010/10/06/accepted PY - 2010/10/8/entrez PY - 2010/10/12/pubmed PY - 2011/1/7/medline SP - 36 EP - 36 JF - Journal of hematology & oncology JO - J Hematol Oncol VL - 3 N2 - 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. SN - 1756-8722 UR - https://www.unboundmedicine.com/medline/citation/20925957/Pharmacokinetic_targeting_of_intravenous_busulfan_reduces_conditioning_regimen_related_toxicity_following_allogeneic_hematopoietic_cell_transplantation_for_acute_myelogenous_leukemia_ L2 - https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-3-36 DB - PRIME DP - Unbound Medicine ER -