Randomized Trial of Myeloablative Conditioning Regimens: Busulfan Plus Cyclophosphamide Versus Busulfan Plus Fludarabine

• Published in: Journal of clinical oncology Vol. 31; no. 6; pp. 701 - 709
• Main Authors: Lee, Je-Hwan, Joo, Young-Don, Kim, Hawk, Ryoo, Hun Mo, Kim, Min Kyoung, Lee, Gyeong-Won, Lee, Jung-Hee, Lee, Won-Sik, Park, Jae-Hoo, Bae, Sung-Hwa, Hyun, Myung Soo, Kim, Dae-Young, Kim, Sung-Doo, Min, Young Joo, Lee, Kyoo-Hyung
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.02.2013
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Busulfan - adverse effects; Busulfan - therapeutic use; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Drug Therapy, Combination; Female; Gastroenteritis - etiology; Graft vs Host Disease - etiology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Humans; Leukemia - therapy; Male; Medical sciences; Middle Aged; Multivariate Analysis; Myeloablative Agonists - adverse effects; Myeloablative Agonists - therapeutic use; Myelodysplastic Syndromes - therapy; Survival Analysis; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome; Tumors; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; Young Adult; Antineoplastic agent; Purine nucleotide; Alkanediol; Nucleotide analog; Alkanesulfonic acid; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Randomization; Cancerology; Fludarabine; Antimetabolic; Nitrogen mustard; Clinical trial; Myelosuppression; Fluorine Organic compounds; Busulfan; Conditioning; Comparative study
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2011.40.2362

We conducted a phase III randomized clinical trial to compare two myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) in patients with leukemia and myelodysplastic syndrome. After randomization, 64 patients received busulfan (3.2 mg/kg per day × 4 days) plus cyclophosphamide (60 mg/kg per day × 2 days; BuCy), and 62 patients received busulfan (same dose and schedule) plus fludarabine (30 mg/m(2) per day × 5 days; BuFlu). The median age was 41 years (range, 17 to 59 years). Five patients in the BuFlu arm experienced graft failure (primary, n = 1; secondary, n = 4). At 4 weeks after HCT, the median percentage of recipient hematopoietic chimerism was significantly greater in the BuFlu arm (0% v 5.5%; P < .001), and complete donor chimerism was greater in the BuCy arm (97.2% v 44.4%; P < .001). Severe (grade 3 or higher) infection and gastrointestinal adverse events were significantly more common in the BuCy arm, but the frequencies of hepatic adverse events were similar in the two arms. Nonrelapse mortality was similar in the two arms, but the BuCy arm had better overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS; OS at 2 years, 67.4% v 41.4%, P = .014; RFS, 74.7% v 54.9%, P = .027; EFS, 60.7% v 36.0%, P = .014). Our results indicate that the BuFlu regimen is not a suitable replacement for the BuCy regimen in young adults who are eligible for myeloablative conditioning therapy for allogeneic HCT.