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.
Highlights
Ongoing investigation aims to preserve efficacy, but reduce morbidity and mortality associated with conditioning therapy for allogeneic hematopoietic cell transplantation (HCT)
Recognizing the adverse outcomes potentiated by variation in bioavailability of oral busulfan, as well as increased toxicity from aberrant metabolism of cyclophosphamide, there was a shift in the institutional practice at our center, wherein those consecutive acute myelogenous leukemia (AML) patients transplanted from 2004 onward received intravenous PK-targeted busulfan combined with fludarabine (t-IV Bu/Flu) as conditioning therapy
We aimed to compare these outcomes to a historical cohort of AML patients, who received Busulfan and Cyclophosphamide (Bu/Cy) as conditioning therapy in a single institution
Summary
Ongoing investigation aims to preserve efficacy, but reduce morbidity and mortality associated with conditioning therapy for allogeneic hematopoietic cell transplantation (HCT). Seminal work has demonstrated variation in bioavailability of oral busulfan (Bu), and the correlation between busulfan exposure and both toxicity including hepatic veno-occlusive disease, [1] as well as graft rejection and primary disease relapse.(8, 9) In the setting of both oral and intravenous administration of busulfan, inter-patient variation is observed [2]. Our center adopted an approach of pharmacokinetic-targeted IV Bu/Flu from 2004 onward as a uniform conditioning strategy in the setting of allogeneic transplantation for acute myelogenous leukemia. As the regimen appears to result in reduced treatment related toxicity compared to our center’s historical experience with oral busulfan and cyclophosphamide, we aimed to confirm these observations in a comparative analysis of outcomes of AML patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
