Examining treatment responses of diagnostic marrow in murine xenografts to predict relapse in children with acute lymphoblastic leukaemia.
Br J Cancer
; 123(5): 742-751, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32536690
ABSTRACT
BACKGROUND:
While current chemotherapy has increased cure rates for children with acute lymphoblastic leukaemia (ALL), the largest number of relapsing patients are still stratified as medium risk (MR) at diagnosis (50-60%). This highlights an opportunity to develop improved relapse-prediction models for MR patients. We hypothesised that bone marrow from MR patients who eventually relapsed would regrow faster in a patient-derived xenograft (PDX) model after induction chemotherapy than samples from patients in long-term remission.METHODS:
Diagnostic bone marrow aspirates from 30 paediatric MR-ALL patients (19 who relapsed, 11 who experienced remission) were inoculated into immune-deficient (NSG) mice and subsequently treated with either control or an induction-type regimen of vincristine, dexamethasone, and L-asparaginase (VXL). Engraftment was monitored by enumeration of the proportion of human CD45+ cells (%huCD45+) in the murine peripheral blood, and events were defined a priori as the time to reach 1% huCD45+, 25% huCD45+ (TT25%) or clinical manifestations of leukaemia (TTL).RESULTS:
The TT25% value significantly predicted MR patient relapse. Mutational profiles of PDXs matched their tumours of origin, with a clonal shift towards relapse observed in one set of VXL-treated PDXs.CONCLUSIONS:
In conclusion, establishing PDXs at diagnosis and subsequently applying chemotherapy has the potential to improve relapse prediction in paediatric MR-ALL.
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Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
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Protocolos de Quimioterapia Combinada Antineoplásica
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Animals
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article