Clofarabine has been shown to effectively induce remission in children with refractory
leukemia. We conducted a prospective trial (clinicval.trials.gov NCT01025778) to explore the use of
clofarabine-based
chemotherapy as a bridge-to-transplant approach. Children with refractory acute
leukemia were enrolled to receive two induction courses of
clofarabine,
etoposide, and
cyclophosphamide (CloEC). Responding patients were scheduled for T-cell depleted haploidentical
hematopoietic stem cell transplantation (HSCT). The primary objective was to improve survival by achieving sufficient disease control to enable
stem cell transplantation. Secondary objectives were to evaluate safety and toxicity. Seven children with active disease entered the study. Two children responded to induction courses and underwent
transplantation. Five children did not respond to induction: one died in progression after the first course; two received off-protocol
chemotherapy and were transplanted; and two succumbed to progressive
leukemia. All transplanted children engrafted and no acute skin graft-versus-host disease > grade I was observed. One child is alive and well 7.5 years after the first CloEC course. One child developed fulminant adenovirus
hepatitis and died in continuous complete remission 7 months after start of induction. Two children relapsed and died 6.5 and 7.5 months after enrollment.
Infection was the most common toxicity. CloEC can induce responses in some patients with refractory acute
leukemia but is highly immunosuppressive, resulting in substantial risk of life-threatening
infections. In our study, haploidentical HSCT was feasible with sustained engraftment. No clinically significant organ toxicity was observed. Also, repeating CloEC probably does not increase the chance of achieving remission.