Integrated Risk Stratification Using Minimal Residual Disease and Sentinel Genetic Alterations in Pediatric Acute Lymphoblastic Leukemia
Menée auprès d'une cohorte de 3 113 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë (durée médiane de suivi : 7 ans), cette étude montre que l'analyse conjointe du niveau de maladie résiduelle minimale et des altérations génétiques des cellules cancéreuses permet d'améliorer la stratification des patients
Treatment of pediatric acute lymphoblastic leukemia (ALL) has provided a paradigm for cancer therapy since 1948, when Farber and Diamond first demonstrated that chemotherapy could induce remission in human cancer. Once curative therapies for ALL were developed, age and WBC count at diagnosis were identified as important prognostic factors that were predictive of response and outcome. It was later found that early response to therapy—as measured by morphologic clearance of blasts from the blood or marrow during induction therapy—was a strong predictor of outcome. It is now recognized that detection of minimal residual disease (MRD) by either PCR amplification of clonotypic IG/TCR gene rearrangements or flow cytometric detection of leukemia-associated phenotypes is perhaps the strongest predictor of event-free survival (EFS) and overall survival (OS). The presence of specific recurrent sentinel genetic lesions in leukemia cells is also a powerful prognostic factor. There is general agreement, not universal, that good risk factors include ETV6-RUNX1 fusion and high hyperdiploidy and/or favorable chromosome trisomies, whereas poor risk factors include BCR-ABL1 fusion, KMT2A (MLL) gene fusions, intrachromosomal amplification of chromosome 21 (iAMP21), and hypodiploidy.
Journal of Clinical Oncology , éditorial en libre accès, 2016