Outcome of childhood acute lymphoblastic leukemia with induction failure treated by the Japan Association of Childhood Leukemia Study (JACLS) ALL F-protocol

Background. Children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) after induction therapy (induction failure: IF) have a poor prognosis; however, there have been few prospective studies in patients with IF. Patients and Methods. Between April 1997 and March 2005, 27 of 1,237 leukemic patients (2.2%) failed to achieve CR after four- or five-drug induction therapy. Twenty-three of these patients entered the F-protocol study, which mainly consisted of acute-myeloid-leukemia-oriented chemotherapy followed by scheduled hematopoietic cell transplantation (HCT). Results. Seventeen (73.9%) of the 23 patients responded to re-induction chemotherapy with CR. Of note, 15 (93.8%) of 16 patients with Philadelphia-chromosome-negative (non-Ph⁺) ALL achieved CR; in contrast, only 2 (28.6%) of 7 Ph ⁺ patients achieved CR. Fourteen (82.4%) of 17 patients remained in CR (CCR) until their scheduled HCT, 12 of the 14 with CCR underwent HCT as scheduled, and 6 patients remain in first CR after a median of 78 months (range, 49-107 months). The 5-year overall survival (OS) rates of 16 patients with non-Ph⁺ and 7 patients with Ph⁺ were 43.8±12.4% and 14.3±13.2%, respectively (P=0.012). The 5-year OS rate of the 17 patients who obtained CR by re-induction therapy and the 6 who did not were 47.1±12.1% and 0%, respectively (P<0.001). Conclusion. Acute-myeloid-leukemia-oriented chemotherapy followed by scheduled HCT is a promising treatment strategy for non-Ph⁺ ALL patients with IF.