AIM: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). METHODS: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses. RESULTS: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10-3), HR cytogenetics and TP53 alterations in BCP-ALL. CONCLUSION: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT. TRIAL REGISTRATION: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348.

• Klíčová slova
• Acute lymphoblastic leukaemia, High-risk, Minimal residual disease, Outcomes, Stem cell transplantation,
• MeSH
• časové faktory MeSH
• dítě MeSH
• doba přežití bez progrese choroby MeSH
• genová dávka MeSH
• hodnocení rizik MeSH
• karyotyp MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• lymfoblastická leukemie-lymfom z prekurzorových T-buněk diagnóza   genetika   mortalita   terapie   MeSH
• mladiství MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• nemoc štěpu proti hostiteli etiologie   MeSH
• pre-B-buněčná leukemie diagnóza   genetika   mortalita   terapie   MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• recidiva MeSH
• reziduální nádor MeSH
• rizikové faktory MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH