Risk factors of central nervous system relapse in mantle cell lymphoma

Abstract

Central nervous system (CNS) relapse has not been extensively studied in mantle cell lymphoma (MCL). We retrospectively analyzed the risk factors and pattern of CNS relapse in consecutive patients with MCL. We identified 142 cases of MCL treated from 1980 to 2011. Median age at diagnosis was 68 years; 82% of patients had advanced stage; extranodal disease was reported in 89% of cases and high serum lactate dehydrogenase (LDH) in 40%. Fourteen patients (10%) did not receive treatment at diagnosis. Chemotherapy was administered to 125 patients (88%), in 21 cases (15%) including drugs penetrating into the CNS or given intrathecally; 49 patients (35%) had rituximab. Ten patients had front-line autologous transplant. After a median follow-up of 7.9 years, CNS relapse occurred in 11 cases (7.8%) at a median of 13.8 months. Actuarial risk of CNS relapse was higher in patients with elevated LDH (p = 0.002), higher International Prognostic Index (IPI) score (p = 0.018) and blastoid histology (p < 0.0001). Blastoid histology retained significance at multivariate analysis. Median survival after CNS relapse was 6.3 months. No front-line treatment reduced the risk of CNS relapse. Our analysis confirms the poor outcome of MCL after CNS relapse and may allow the identification of patients needing prophylaxis of CNS relapse.

The risk of CNS involvement in aggressive lymphomas in the rituximab era

“…Among the several clinical variables at diagnosis, only blastoid variant, high MCL IPI (MIPI) score, high Ki-67 and high LDH serum level are predictors of CNS [27]. The results were also similar when the analysis was limited to the risk of CNS involvement at first relapse: blastoid variant and elevated serum LDH levels retained their prognostic impact [28].…”

“…In four retrospective studies, the median time of CNS relapse from diagnosis was 12-51 months and the median survival from the time of CNS involvement was 2-9 months [27][28][29][30][31]. Although CNS relapse in MCL has not been investigated extensively, its frequency appears to be higher than that observed in indolent lymphoma subtypes and may vary widely (4-26%) in different case series, being comparable to that of DLBCL [29,32,33].…”

“…CNS relapse is often a feature of relapsed/ refractory MCL and is mainly associated with systemic relapse [29]. In a recent trial, Conconi et al analyzed 142 MCL patients: CNS relapse was observed in 11 of 142 patients (7.8%; 95% CI: 3.9-13.4%) [28]. CNS involvement occurred after a median of 13.8 months (range: 3.7-95 months).…”

“…CNS relapse in non-Hodgkin lymphoma treated in the rituximab era. Elevated LDH, high MIPI, blastoid [28] Gill et al B l a s t o i d [27] Ferrer et al Blastoid, elevated LDH, >2 extranodal [29] Cheah et al High aaIPI, elevated LDH, >1 extranodal [51] Benevolo et al Special Report Benevolo, Chiappella & Vitolo disease [51]; however, its prophylactic effect was no longer detectable if given together with rituximab, as was observed in the MInT study where patients treated with CHOEP experienced fewer relapses than patients given CHOP. This effect was also lost when rituximab was added to CHOEP and CHOP [52].…”

“…CNS relapse had a dismal impact on the outcome: median survival after CNS relapse was 6.3 months (range: 1.5-78 months). Blastoid variant, high MIPI score, high Ki-67 and high LDH serum level are predictors of CNS involvement [28].…”