Systematic Review and Meta-Analysis of Factors Associated with CNS Involvement in Mantle Cell Lymphoma
Authors: Joseph Varughese Vivek , Selene Insija , Pavy Michael , Cassada Ronald , Iragavarapu Chaitanya , Jose Jemin , Elengickal Joseph 
Published: December 2023

Background: Mantle cell lymphoma is a mature B -cell Non-Hodgkin's Lymphoma with a variable clinical course. CNS involvement in mantle cell lymphoma is usually associated with recurrent/refractory disease but can also complicate its initial presentation. CNS involvement carries a dismal prognosis. The Mantle Cell Lymphoma International Prognostication Index includes age, ECOG status, LDH, and WBC count to prognosticate the disease. This study aimed to systematically review existing real-world studies to find statistically significant factors associated with CNS metastasis in Mantle Cell Lymphoma.

Evidence acquisition: we performed a comprehensive database search on four major databases (Pubmed, Embase, Google Scholar, and Cochrane Central). Then, a team of independent reviewers selected relevant studies and extracted the data. 54 studies were reviewed from the databases, and 14 were found eligible for the systematic review. Five of the studies were retrospective studies, which were included in the meta-analysis. Revman 5.4 statistical analysis software was used for the analysis.

Results: A total of 857 patients with Mantle Cell Lymphoma were involved in the meta-analysis :( Chihara et al): 608, (Ferrer et al): 82, (Cheah et al): 105 and (Gill et al): 62. Of these, 107 patients had CNS involvement: (Chihara et al): 33, (Ferrer et al): 12, (Cheah et al): 57 and (Gill et al): 5. Mantle cell lymphoma patients with staging III/IV disease were found to be associated more with CNS metastasis (OR 4.51 (1.56- 8.23) compared to stages I/II. Serum LDH level more than the upper limit of normal was found to have a statistically significant association with CNS involvement (OR 4.27 {1.17-15.51}: Heterogeneity: Tau2= 0.89, df=2 (p=0.009), I2= 79%, Overall effect size Z=2.43 p= 0.02) among Mantle Cell lymphoma patients. Ki 67 expression &gt; 50% had increased odds for CNS metastasis (OR 2.83 {1.67 -4.79}: Heterogeneity: Tau2=0.43, Chi2=0.34, df=2 p=0.84); I2=70%, Overall effect size Z=3.87 p=0.0003). Blastoid/ pleomorphic histologic subtypes had significant odds of leading to CNS metastasis compared to the classic MCL subtypes (OR 5.27 {3.07- 9.06}, Heterogeneity: Tau2=0.03, Chi2=3.2, df= 3 (p=0.35), I2= 9%, Overall effect size Z= 6.03 p=0.0001). Serum Beta 2 microglobulin levels and WBC count at initial presentation had no statistically significant association with CNS involvement.

CONCLUSION: As per the current NCCN guidelines, CNS chemoprophylaxis is indicated for Diffuse Large B- Cell Lymphoma (DLBCL) with high-risk features (as per the CNS international prognostication index). CNS involvement in Mantle Cell Lymphoma has a dismal prognosis. The findings of this meta-analysis underscore a noteworthy correlation between certain risk factors and CNS involvement in Mantle Cell Lymphoma. Additional studies are needed to determine the impact of chemoprophylaxis in patients with these high-risk features.