Favorable outcome of hematopoietic stem cell transplantation using a targeted once-daily IV busulfan fludarabine etoposide regimen in pediatric and infant ALL patients

Favorable outcome of hematopoietic stem cell transplantation using a targeted once-daily IV busulfan fludarabine etoposide regimen in pediatric and infant ALL patients

Favorable outcome of hematopoietic stem cell transplantation using a targeted once-daily IV busulfan fludarabine etoposide regimen in pediatric and infant ALL patients

(구연):
Release Date : 2013. 10. 19(토)
Ji Won Lee¹, Hyoung Jin Kang¹, Sungjin Kim¹, SeungHwan Lee², Kyung-Sang Yu², Nam Hee Kim¹, Mi Kyoung Jang¹, Hyery Kim¹, Sang Hoon Song³, Kyung Duk Park¹, Hee Young Shin¹, In-Jin Jang³, Hyo Seop Ahn¹
¹Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea ²Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea ³Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
Ji Won Lee¹, Hyoung Jin Kang¹, Sungjin Kim¹, SeungHwan Lee², Kyung-Sang Yu², Nam Hee Kim¹, Mi Kyoung Jang¹, Hyery Kim¹, Sang Hoon Song³, Kyung Duk Park¹, Hee Young Shin¹, In-Jin Jang³, Hyo Seop Ahn¹
¹Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea ²Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea ³Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

Abstract

b>Background:/b> Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan based conditioning regimen with cyclophosphamide has been used as an alternative to TBI based regimen. Etoposide has been widely used in hematopoietic stem cell transplantation (HSCT) because of its anti-leukemic effect, and a conditioning regimen containing busulfan, cyclophosphamide and etoposide (BuCyVP) was used in many studies. 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. We evaluated the outcome of HSCT using a targeted once-daily intravenous (IV) busulfan fludarabine etoposide (BuFluVP) regimen in pediatric and infant ALL. b>Methods:/b> A retrospective review was done on children who underwent HSCT with a targeted once daily IV BuFluVP regimen. Busulfan (≥ 1 year-120 mg/m² and 1 year-80 mg/m²) was administered as the first dose on day -8, and targeted dose of busulfan was used according to the TDM results on day -7 ~ -5. b>Results:/b> 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 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). 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, i>P/i>=0.95). Eleven patients (33.3%) were infants at diagnosis, and OS of these patients was 81.8%. b>Conclusion:/b> 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.

Keywords: busulfan, fludarabine, therapeutic drug monitoring