Refractory acute lymphoblastic leukemia in Chinese children: bridging to stem cell transplantation with clofarabine, cyclophosphamide and etoposide

Refractory or relapsed acute lymphoblastic leukemia (r/r ALL) represents the leading cause of cancer mortality in children. Clofarabine is effective in inducing remission thus enabling bridging to hematopoietic stem cell transplantation (HSCT). We report the results in treating Hong Kong Chinese pediatric patients with r/rALL by clofarabine/cyclophosphamide/etoposide (CLO-218) combination therapy. A retrospective review of patients treated between January 2009 and December 2014 in the two tertiary referral pediatric oncology units in Hong Kong. Thirteen patients were identified. All were Chinese and seven were male. Median age at clofarabine treatment was 8 years and the median duration of follow-up was 10 months. Nine patients had B-ALL and four had T-ALL. All were refractory to the preceding regimen(s). The median number of prior treatment regimens was 2; two patients had previous HSCT. Complete remission (CR) was achieved in five patients, Complete remission with incomplete counts (CRi) in two, PR in two, and non-remission (NR) in two. All four patients with T-ALL responded with three patients achieving CR. Eight out of nine patients who responded could be bridged to HSCT. Among those who were transplanted, four remained alive and in remission, three relapsed post-HSCT, and one died from transplant-related mortality. Treatment toxicities were common including febrile neutropenia in all subjects and culture-proven bacteremia in five patients. Hepatotoxicity was mild and reversible with no case of veno-occlusive disease. The clofarabine-based regimen is a promising strategy to induce disease remission in r/rALL and bridge to HSCT. Septic complications are, however, frequent necessitating prompt management with adequate supportive care in specialized centers.