High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation
Date
2013
Authors
Marshall, G.
Dalla Pozza, L.
Sutton, R.
Ng, A.
de Groot-Kruseman, H.
van der Velden, V.
Venn, N.
van den Berg, H.
de Bont, E.
Egeler, R.
Editors
Advisors
Journal Title
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Type:
Journal article
Citation
Leukemia, 2013; 27(7):1497-1503
Statement of Responsibility
G M Marshall, L Dalla Pozza, R Sutton, A Ng, H A de Groot-Kruseman, 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 and R Pieters
Conference Name
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-Mu¨ nster 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.
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© 2013 Macmillan Publishers Limited