title: Bortezomib, Dexamethasone, Mitoxantrone, and Vinorelbine (BDMV): An Active Reinduction Regimen for Children With Relapsed Acute Lymphoblastic Leukemia and Asparaginase Intolerance.
abstract: Children with relapsed acute lymphoblastic leukemia (ALL) typically receive vincristine-prednisone-L-asparaginase-doxorubicin reinduction chemotherapy similar to contemporary induction regimens. However, up to 20% of patients are unable to receive vincristine-prednisone-L-asparaginase-doxorubicin secondary to asparaginase intolerance. We report our experience with a promising reinduction regimen for children with relapsed ALL who are unable to receive asparaginase.
  
  
  
  This is a single institution, retrospective review of the safety and activity of bortezomib, dexamethasone, mitoxantrone, and vinorelbine (BDMV) in patients with relapsed ALL. Complete remission and adverse events after reinduction were study endpoints. Patients treated with BDMV between 2012 and 2015 were identified. Response and adverse events (AEs) were assessed by review of medical records. Standard response criteria were used and AEs were graded based on NCI CTCAEv4.0.
  
  
  
  Seven of 10 patients achieved complete remission after 1 cycle of BDMV, with 4 achieving minimal residual disease negativity. The most common ≥grade 3 nonhematological toxicities were infection (91%), gastrointestinal (45%), metabolic (45%), and cardiovascular (9%).
  
  
  
  BDMV is an active reinduction regimen for children with relapsed ALL who cannot receive asparaginase. The toxicity profile is as expected for this patient population. Further prospective clinical trials are warranted to evaluate the safety and efficacy of BDMV.
authors.affiliation: *Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles†Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Kee K
authors.initials: KK
authors.lastname: Yeo
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: Cecilia H
authors.initials: CH
authors.lastname: Fu
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
authors.forename: Weili
authors.initials: W
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects; D000069286:Bortezomib / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D012008:Recurrence; D012074:Remission Induction / Q000379:methods*; D012189:Retrospective Studies; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult
chemical_list: D014747:Vinblastine; D000069286:Bortezomib; D003907:Dexamethasone; D008942:Mitoxantrone; D001215:Asparaginase; D000077235:Vinorelbine