Impact of central nervous system (CNS) prophylaxis on the incidence of CNS relapse in patients with high-risk diffuse large B cell/follicular grade 3B lymphoma

Hanne Kuitunen,Elina Kaprio,Taina Turpeenniemi-Hujanen,Ville Makkonen,Milla Kuusisto,Kirsi-Maria Haapasaari,Outi Kuittinen,Saila Kauppila,Esa Jantunen,Peeter Karihtala

doi:10.1007/s00277-020-04140-0

Abstract

Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.

Highlights

Diffuse large B cell lymphoma (DLBCL) is the most frequent form of non-Hodgkin lymphoma, accounting for 25–58% of all NHL cases [1, 2]
The incidence of central nervous system (CNS) recurrence varies from 5 to 25% in DLBCL [8,9,10,11,12,13,14]. After facing this problem in Oulu University Hospital, we incorporated into our treatment algorithm an intravenous high-dose methotrexate (MTX)-based CNS prophylaxis to patients at high risk of CNS relapse according to evaluation by clinical risk factors
We report on a retrospective analysis of 95 high-risk DLBCL patients treated with R-CHOP, RCEOP or R-CHOEP immunochemotherapy with or without CNS prophylaxis during 2006–2012, mainly in Oulu University Hospital

Summary

Introduction

Diffuse large B cell lymphoma (DLBCL) is the most frequent form of non-Hodgkin lymphoma, accounting for 25–58% of all NHL cases [1, 2]. DLBCL is responsive to chemotherapy and with current immunochemotherapy regimen, R-CHOP or its derivatives, about 60% of patients achieve long-term disease-free survival [3,4,5]. The incidence of CNS recurrence varies from 5 to 25% in DLBCL [8,9,10,11,12,13,14]. After facing this problem in Oulu University Hospital, we incorporated into our treatment algorithm an intravenous high-dose methotrexate (MTX)-based CNS prophylaxis to patients at high risk of CNS relapse according to evaluation by clinical risk factors

Methods

Results

Conclusion