The safety and efficacy of clofarabine in combination with high-dose cytarabine and total body irradiation myeloablative conditioning and allogeneic stem cell transplantation in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia

Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 – 52 mg/m ² ), cytarabine 1000 mg/m ² , and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1–22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors. Probabilities of neutrophil, platelet engraftment, acute GvHD, and chronic GvHD were 94%, 84%, 49%, and 30%, respectively. Probability of day 100 TRM was 8.1%. 2-year EFS (event free survival) and OS (overall survival) were 38.6% (CI ₉₅ : 23–54%), and 41.3% (CI ₉₅ : 25–57%). Multivariate analysis demonstrated overt disease at time of transplant (relative risk (RR) 3.65, CI ₉₅ : 1.35–9.89, P = 0.011) and umbilical cord blood source (RR 2.17, CI ₉₅ : 1.33–4.15, P = 0.019) to be predictors of worse EFS/OS. This novel myeloablative conditioning regimen followed by alloSCT is safe and well tolerated in CAYA with very poor-risk ALL or AML. Further investigation in CAYA with better risk ALL and AML undergoing alloSCT is warranted.