The Magnitude of Lactate Dehydrogenase Elevation As a Predictive Factor for Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma

Introduction: The incidence of central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is approximately 5%. Although the introduction of rituximab for the treatment of DLBCL has reduced the risk of CNS relapse, the median overall survival of these patients remains only few months, emphasizing the need to accurately identify at-risk patients, screen for CNS disease, and develop effective therapeutic/prophylactic strategies.

Aim: To identify risk factors for CNS relapse in patients with DLBCL.

Methods: Retrospective analysis of patients with DLBCL diagnosed from January 2012 to December 2017 at a Cancer Institute. Patients with exclusive extranodal (EN) disease were excluded. Factors associated with CNS relapse were evaluated using Chi-square, Fisher's Exact Test, Mann-Withney U or T-Test, according to variable types and distributions. Survival was evaluated by Kaplan-Meier method and groups were compared by Log-rank test. Independent predictive factors were identified using Logistic Regression. A p value < 0.05 was considered statistically significant.

Results: Four hundred and seventy-nine patients were identified, 122 were excluded due to exclusive EN disease, and 357 patients were included in the study. With a median follow-up of 33 months, there were 10 (3%) CNS relapses. According to International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI), 5 (50%) of these patients were classified as high risk, 4 (40%) intermediate risk and 1 (10%) low risk. Patients who development CNS involvement were significantly younger (57 vs. 65 years, p=0.036), presented higher levels of lactate dehydrogenase (LDH) (median 738 vs. 282 U/L, p<0.001) and lower levels of hemoglobin (median 10,3 vs. 12,1 g/dL, p=0.010) at diagnosis. No differences were found regarding to performance status, stage or number of EN areas. Two patients (18%) in the CNS relapse group had done CNS prophylaxis versus twenty two (6,3%) patients in the group without CNS relapse. In multivariate analysis, LDH >600 was the only independent predictive factor (HR 15.3, CI 95% 3.5 - 65.8, p<0.001). Overall survival in CNS relapse group was 22 months, versus not reached (p<0.001).

Conclusion: Although CNS-IPI is a robust model to estimate the risk of CNS relapse, it does not capture the full spectrum of those at high risk. Other clinical risk factors and biomarkers beyond this model might play an important role in this setting, such as the magnitude of LDH elevation