Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL)
Menée sur 608 patients atteints d'un lymphome à cellules du manteau diagnostiqué entre 1994 et 2012 (âge médian : 67 ans, durée médiane de suivi : 42,7 mois), cette étude met en évidence une forte association entre un niveau élevé d'expression de l'antigène Ki-67 et le risque de récidive au niveau du système nerveux central
Background : Central nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach.
Patients and Methods A total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis.
Results None of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% (95%CI: 3.7-8.0%). Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk mantle cell lymphoma international prognostic index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67≥30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95%CI: 1.9-19.4, P=0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67≥30 was 25.4% (95%CI: 13.5-39.1), while that in the patients with Ki-67<30 was 1.6% (95%CI: 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.
Summary High Ki-67 is strongly associated with the risk of CNS relapse in patients with MCL. Evaluation of CNS involvement at diagnosis and the development of new prophylactic treatment strategies for CNS involvement are mandatory in patients with high Ki-67.
Annals of Oncology , résumé, 2015