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

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. HaberT. Révész, F. Alvaro, R. Suppiah, M. D. Norris, R. Pieters

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54 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1497-1503
Number of pages7
JournalLeukemia
Volume27
Issue number7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • Acute lymphoblastic leukemia
  • Bone marrow transplant
  • Childhood
  • Drug toxicity
  • MRD testing

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