High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

• DOI: 10.1038/leu.2013.44
• Publication Date: 2013-02-14T07:40:37Z
• Authors: G M Marshall; L Dalla Pozza; R Sutton; A Ng; H A de Groot-Krus...; V H van der Velden; N C Venn; H van den Berg; E S J M de Bont; R Maarten Egeler; P M Hoogerbrugge; G J L Kaspers; M B Bierings; E van der Schoot; J van Dongen; T Law; S Cross; H Mueller; V de Haas; M Haber; T Révész; F Alvaro; R Suppiah; M D Norris; R Pieters
• Keywords: EMC MM-02-72-03; Male; 32 Biomedical and Clinical Sciences; Kaplan-Meier Estimate; T-CELL; anzsrc-for: 1103 Clinical Sciences; 0302 clinical medicine; Risk Factors; MRD testing; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Child; Cancer; Pediatric; Mercaptopurine; Remission Induction; anzsrc-for: 3201 Cardiovascular Medicine and Haematology; Cytarabine; Hematopoietic Stem Cell Transplantation; Hematology; bone marrow transplant; Precursor Cell Lymphoblastic Leukemia-Lymphoma; CRANIAL IRRADIATION; Combined Modality Therapy; drug toxicity; 3. Good health; Treatment Outcome; Vincristine; anzsrc-for: 3202 Clinical sciences; 6.1 Pharmaceuticals; Child, Preschool; Female; CHILDRENS ONCOLOGY GROUP; 4.2 Evaluation of markers and technologies; Homologous; Adolescent; Childhood Leukemia; Pediatric Cancer; Clinical Trials and Supportive Activities; 610; MINIMAL RESIDUAL DISEASE; acute lymphoblastic leukemia; 03 medical and health sciences; Rare Diseases; anzsrc-for: 32 Biomedical and Clinical Sciences; Clinical Research; Asparaginase; Humans; Preschool; CLINICAL-SIGNIFICANCE; Cyclophosphamide; childhood; anzsrc-for: 3211 Oncology and Carcinogenesis; Transplantation; Daunorubicin; anzsrc-for: 1112 Oncology and Carcinogenesis; Infant; STEM-CELL TRANSPLANTATION; EMC MM-02-54-03; 3211 Oncology and Carcinogenesis; Childhood; ONCOL 2: Age-related aspects of cancer NCMLS 2: Immune Regulation; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE MITOXANTRONE; Orphan Drug; AIEOP-BFM; Methotrexate; 3201 Cardiovascular Medicine and Haematology; Prednisone; GENE REARRANGEMENTS

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.