INTRODUCTION
Despite improvement in survival of children with acute leukemia (AL), a significant number of such patients still experience primary or secondary resistance to treatment.1,2 Children failing to achieve remission and those relapsing after previous allogeneic hematopoietic stem cell transplantation have a short life expectancy, and palliative treatment remains the only reasonable option, because in many cases escalation of conventional chemotherapy is no longer effective. Thus far, cell/immune therapies are applied primarily in B precursor acute lymphoblastic leukemia (ALL), whereas refractory T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloblastic leukemia (AML) still represent an unmet challenge.3 Allogeneic hematopoietic stem cell transplantation (HSCT) seems to improve survival in children with high-risk acute leukemia. Better survival can in part be mediated by the graft-versus-leukemia (GvL) effect together with the anti-leukemic effect of the conditioning regimen. However, the efficacy of allogeneic HSCT is inversely correlated to the tumor burden. In patients without at least morphological remission at the time of transplantation, the risk of subsequent relapse is very high. Clofarabine has been shown to potently induce remissions in refractory cases of pediatric acute leukemia, both when given as a single drug and in combination with etoposide and cyclophosphamide. In the Nordic countries, clofarabine has not been incorporated in the primary treatment of acute leukemia in children, thus leukemic cells from patients who are refractory to multiple multidrug regimes have usually not been exposed to clofarabine. Still, responses induced by clofarabine-containing drug combinations are often transient in character. Nevertheless, even a temporary decrease in tumor load before an allogeneic HSCT could theoretically increase the potency of the GvL effect in reducing the risk of relapse, making this treatment modality a potential consolidation of clofarabine-induced responses. The short duration of clofarabine-elicited responses requires precise timing of the allogeneic HSCT. Transplantation with haploidentical donors offers such precision and may also lead to an enhanced GvL effect due to the HLA disparity between the donor and recipient.4-6 Our aim was to evaluate the safety and toxicity of intensified clofarabine-based multidrug remission induction for heavily pretreated children with r/r AL, and also determine the potential of this approach to bridge these patients to a promptly timed haploidentical HSCT.