Detection of MRD may predict the outcome of patients with Philadelphia-chromosome positive ALL treated with tyrosine kinase inhibitors plus chemotherapy
Menée sur 76 patients atteints d'une leucémie lymphocytaire aiguë Ph+, cette étude évalue l'intérêt d'évaluer la maladie résiduelle minimale, par cytométrie en flux multi-paramètres et PCR en temps réel, pour identifier les patients susceptibles de bénéficier d'une intensification du traitement à l'aide d'imatinib ou de dasatinib
From April 2001 to March 2011, 122 patients with newly diagnosed Ph+ ALL were treated with hyperCVAD + imatinib (n= 54) and hyperCVAD + dasatinib (n= 68). 115 (94%) achieved CR including 101 patients who achieved it with only one induction course and had at least one minimal residual disease (MRD) assessment; 25 patients underwent an allogeneic stem cell transplant in first CR and were excluded, leaving 76 patients as the subject of this report. MRD monitoring by multi-parameter flow cytometry (MFC) and quantitative polymerase chain reaction (RQ-PCR) was performed at the end of induction and at approximately 3 month intervals thereafter. Median age for the 76 patients was 54 years (range, 21 – 84 years). There was no difference in survival by achievement of at least a major molecular response (MMR, BCR-ABL/ABL < 0.1%) at CR (p=0.22). Patients achieving MMR at 3, 6, 9, and 12 months had a significantly better survival (p=0.02, p=0.04, and p=0.05, and p=0.01, respectively). Achievement of negative MFC at CR did not predict for improved survival (p=0.2). At 3 and 12 months, negative MRD by MFC was associated with improved survival (p=0.04 and p=0.001). MRD monitoring by PCR and MFC identifies patients who benefit from treatment intensification in first CR. (Registered at clinicaltrials.gov: NCT00390793)
Blood , résumé, 2013