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

TLDR: Children with acute lymphoblastic leukemia 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.

Abstract: 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. Pediatr Blood Cancer 2010; 54:71–78. © 2009 Wiley-Liss, Inc.