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. 2022 Oct 13;17(6):159.
doi: 10.3892/mco.2022.2592. eCollection 2022 Dec.

Outcomes of high‑dose methotrexate for CNS prophylaxis in diffuse large B‑cell lymphoma with an intermediate or high CNS‑International Prognostic Index: A single‑center retrospective cohort study

Mubarak Al-Mansour  1   2   3 , Ahmed Absi  2   3   4 , Roula Al-Μufti  1   3 , Majed Alahmadi  2   3   4 , Ihab El-Ηemaidi  2   3   4 , Sameer Alamoudi  2   3   4 , Saleem Eldadah  2   3 , Syed Sameer Aga  2   3 , Muhammed A Khan  2   3 , Ahmed Alsaeed  2   3   4
Affiliations

Outcomes of high‑dose methotrexate for CNS prophylaxis in diffuse large B‑cell lymphoma with an intermediate or high CNS‑International Prognostic Index: A single‑center retrospective cohort study

Mubarak Al-Mansour et al. Mol Clin Oncol. .

Abstract

Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is rare (2-5% of cases), but is a devastating complication with a poor survival rate. The administration of high-dose methotrexate (HDMTX) for CNS prophylaxis in patients with DLBCL is controversial and variable in the literature. The present study aimed to evaluate the clinical outcomes of HDMTX CNS prophylaxis in patients with intermediate and high CNS-International Prognostic Index (IPI) DLBCL using real-world data. An observational retrospective cohort study was conducted of all patients with intermediate and high CNS-IPI DLBCL treated at Princess Noorah Oncology Center (King Abdulaziz Medical City, Jeddah, Saudi Arabia) between January 2010 and December 2020. Patients were treated with HDMTX either intravenously or intrathecally, according to the physician's evaluation of the patient. Data on patient clinical characteristics, CNS relapses, risk factors and survival rates were obtained from hospital records. Data were analyzed using Student's unpaired t-test and the χ2 test to compare the two subgroups, the Kaplan-Meier survival method with log-rank test to calculate and compare the survival rates, and regression analysis to determine the risk factors for CNS relapse and death. The study included 358 patients (n=32 with HDMTX CNS prophylaxis and n=326 without CNS prophylaxis). Patients in the CNS prophylaxis group had a significantly higher CNS relapse rate than those in the non-CNS prophylaxis group (12.5% vs. 1.8%; P=0.008). Patients who received CNS prophylaxis were younger and had an advanced stage of disease, with extranodal involvement and a high serum lactate dehydrogenase level at presentation. CNS prophylaxis was significantly associated with CNS relapse, while relapsed disease was associated with the risk of death (all P<0.05). In conclusion, the present study found that patients with intermediate and high CNS-IPI who received HDMTX CNS prophylaxis did not have fewer CNS relapses; however, those without CNS relapse had higher survival rates. In addition to CNS prophylaxis, Stage of DLBCL and IPI were significantly associated with CNS relapse. Future randomized control trials are needed to evaluate the efficacy of HDMTX CNS prophylaxis in patients with DLBCL.

Keywords: International Prognostic Index; central nervous system; diffuse large B-cell lymphoma; high-dose methotrexate; relapse.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Kaplan-Meier survival curves for the CNS relapses in patients with and without HDMTX CNS prophylaxis. CNS, central nervous system; HDMTX, high-dose methotrexate.
Figure 2
Figure 2
Kaplan-Meier survival curves for overall survival in patients with post-CNS relapse. CNS, central nervous system.
Figure 3
Figure 3
Kaplan-Meier survival curves for overall survival in the study population subgrouped as those with and without CNS relapse. CNS, central nervous system.
Figure 4
Figure 4
Kaplan-Meier survival curves for progression-free survival in the study population.
See this image and copyright information in PMC

References

    1. Linch D. Developments over the last 60 years in diffuse large B-cell lymphomas. Br J Haematol. 2020;191:552–557. doi: 10.1111/bjh.17154. - DOI - PubMed
    1. Harrysson S, Eloranta S, Ekberg S, Enblad G, Jerkeman M, Wahlin BE, Andersson PO, Smedby KE. Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden. Blood Cancer J. 2021;11(9) doi: 10.1038/s41408-020-00403-1. - DOI - PMC - PubMed
    1. Zahid MF, Khan N, Hashmi SK, Kizilbash SH, Barta SK. Central nervous system prophylaxis in diffuse large B-cell lymphoma. Eur J Haematol. 2016;97:108–120. doi: 10.1111/ejh.12763. - DOI - PubMed
    1. Haioun C, Besson C, Lepage E, Thieblemont C, Simon D, Rose C, Tilly H, Sonet A, Lederlin P, Attal M, et al. Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: A GELA study on 974 patients. Groupe d'Etudes des Lymphomes de l'Adulte. Ann Oncol. 2000;11:685–690. doi: 10.1023/a:1008394827806. - DOI - PubMed
    1. Tilly H, Vitolo U, Walewski J, da Silva MG, Shpilberg O, André M, Pfreundschuh M, Dreyling M. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 (Suppl 7):vii78–82. doi: 10.1093/annonc/mds273. ESMO Guidelines Working Group. - DOI - PubMed