Salvage therapy for children with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia

Yuichi Kodama, Atsushi Manabe, Hirohide Kawasaki, Itaru Kato, Keisuke Kato, Atsushi Sato, Kimikazu Matsumoto, Motohiro Kato, Hidefumi Hiramatsu, Hideki Sano, Takashi Kaneko, Megumi Oda, Akiko M. Saito, Souichi Adachi, Keizo Horibe, Shuki Mizutani, Eiichi Ishii, Hiroyuki Shimada

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3 Citations (Scopus)

Abstract

Background: In the tyrosine kinase inhibitor (TKI) era, outcomes after salvage therapy for relapsed or refractory Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remain unclear. Procedure: The clinical courses of 19 patients with relapse (n = 13) or induction failure (n = 6) in the Japanese Pediatric Leukemia/Lymphoma Study Group Ph+ ALL04 study were retrospectively reviewed. Results: Fifteen male and four female patients had a median age of 8 (range 4–15) years at relapse or induction failure. Patients received imatinib in combination with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and methotrexate and cytarabine (MTX/Ara-C) (n = 9), imatinib in combination with other chemotherapy (n = 5), chemotherapy without imatinib (n = 2), imatinib alone (n = 2), or no additional chemotherapy (n = 1). Two patients underwent hematopoietic stem cell transplantation (HSCT) without achieving complete remission (CR) and died of leukemia. The remaining 17 patients achieved CR with salvage therapies and underwent HSCT whilst in CR: 10 patients remain alive in CR, five died of transplantation-related complications, and two died of relapse. In six of seven patients with available data on minimal residual disease (MRD), imatinib in combination with the first course of hyper-CVAD was more effective in achieving a favorable MRD response compared with the Ph+ ALL04 induction regimen. Conclusion: This study suggested that cross-resistance to imatinib failed to develop after conventional chemotherapy. Imatinib in combination with chemotherapy including hyper-CVAD+MTX/Ara-C was effective and safe for relapsed or refractory Ph+ ALL patients who received frontline therapy without imatinib.

Original languageEnglish
Article numbere26423
JournalPediatric Blood and Cancer
Volume64
Issue number8
DOIs
Publication statusPublished - 2017 Aug

Keywords

  • Philadelphia chromosome positive acute lymphoblastic leukemia
  • hyper-CVAD
  • refractory
  • relapse

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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    Kodama, Y., Manabe, A., Kawasaki, H., Kato, I., Kato, K., Sato, A., Matsumoto, K., Kato, M., Hiramatsu, H., Sano, H., Kaneko, T., Oda, M., Saito, A. M., Adachi, S., Horibe, K., Mizutani, S., Ishii, E., & Shimada, H. (2017). Salvage therapy for children with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Pediatric Blood and Cancer, 64(8), [e26423]. https://doi.org/10.1002/pbc.26423