title: High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.
abstract: Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)-Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.
authors: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, UNSW, Sydney, New South Wales, Australia. g.marshall@unsw.edu.au
authors: G M
authors: GM
authors: Marshall
authors: L
authors: L
authors: Dalla Pozza
authors: R
authors: R
authors: Sutton
authors: A
authors: A
authors: Ng
authors: H A
authors: HA
authors: de Groot-Kruseman
authors: V H
authors: VH
authors: van der Velden
authors: N C
authors: NC
authors: Venn
authors: H
authors: H
authors: van den Berg
authors: E S J M
authors: ES
authors: de Bont
authors: R
authors: R
authors: Maarten Egeler
authors: P M
authors: PM
authors: Hoogerbrugge
authors: G J L
authors: GJ
authors: Kaspers
authors: M B
authors: MB
authors: Bierings
authors: E
authors: E
authors: van der Schoot
authors: J
authors: J
authors: van Dongen
authors: T
authors: T
authors: Law
authors: S
authors: S
authors: Cross
authors: H
authors: H
authors: Mueller
authors: V
authors: V
authors: de Haas
authors: M
authors: M
authors: Haber
authors: T
authors: T
authors: Révész
authors: F
authors: F
authors: Alvaro
authors: R
authors: R
authors: Suppiah
authors: M D
authors: MD
authors: Norris
authors: R
authors: R
authors: Pieters
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012074:Remission Induction; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin