Retrospective Analysis of Cerebrospinal Fluid Studies and Intrathecal Methotrexate Treatment in the Setting of Hematologic Malignancies with and without Central Nervous System Involvement: A Comparative Study of Treatment Outcomes and Neurologic Complications
Authors: Tai Derek , Joung Bowon , Koshy-Chenthittayil Sherli , Fay Andrew , Borecky Mick , Park Kiwon , Mendoza Lidia , Akhtari Mojtaba 
Published: December 2024

Background:

CNS involvement in hematologic malignancies, while uncommon, is often associated with serious complications, leading to worse clinical outcomes. In adult patients, diagnostic lumbar puncture (LP) is not routinely performed due to the absence of initial signs or symptoms of CNS involvement. Consequently, intrathecal methotrexate (IT MTX) is often administered prophylactically to patients with high-risk features for CNS invasion. However, the clinical characteristics and incidence of CNS invasion in various hematologic malignancies remain understudied due to the lack of routine LP procedures.

Aim:

We aimed to evaluate the incidence of CNS involvement in patients with hematologic malignancies who received routine lumbar punctures due to high-risk features before receiving prophylactic intrathecal methotrexate.

Methods:

In this single-center retrospective study, we acquired data from adult patients with hematologic malignancies who received intrathecal methotrexate (IT MTX) from January 2010 to July 2024. All patients with hematologic malignancies, including leukemias, lymphomas, and myelomas, were included for routine lumbar puncture (LP) and IT MTX treatment at the time of their hospital admission for: High-risk clinical features for CNS involvement, such as the International Prognostic Index for diffuse large B-cell lymphomas (DLBCL), development of CNS symptoms (e.g., headache, seizure, neuropathy, ptosis, diplopia, and weakness), or previous CSF studies with malignant cells. Positive CNS involvement was determined through CSF flow cytometry and the presence of malignant cells. Patients with solid malignancies or those under the age of 18 were excluded. After the initial LP, all patients received multiple rounds of prophylactic IT MTX as tolerated and deemed clinically appropriate.

Results:

Among 52 eligible patients, the median age was 57 years (range 17-90) including 26 males and 26 females. Upon initial LP and their subsequent cytology, 90.4% of patients (47) did not show CNS involvement despite high-risk features and 9.6% of patients (5) revealed positive CNS involvement. Among patients without CNS involvement, the primary diagnosis includes lymphomas (27) and leukemias (20) with an initial ECOG performance status &lt; 2 (32) and &gt; 2 (15). Among patients with initial CNS involvement after routine LP, patients had leukemias (2), lymphomas (2), and myeloma (1), with an initial ECOG performance status &lt; 2 (2) and &gt; 2 (3). Regarding survival data, 78.7% (37) of patients without initial CNS involvement were alive, and 21.3% (10) were deceased at the end of the treatment course. Among patients with initial CNS involvement, 60% (3) were alive, and 40% (2) were deceased at the end of their treatment course. Of the patients with initial CNS involvement, 80% (4) became CNS negative and 20% (1) remained CNS positive after routine LP. The incidence of CNS involvement was 8.5% (4) for patients who initially had no CNS involvement (p-value = 0.002), with 1 lymphoma and 3 leukemias as the primary hematologic malignancy. Of the 4 patients who developed CNS invasion, 50% (2) became CNS negative, and 50% (2) remained CNS positive (p-value = 0.37), resulting in a prevalence of 4.25%. Overall, 17.3% (9) of all eligible patients had CNS involvement, with 88.9% (8) of CSF studies consistent with their primary hematologic malignancy.

Conclusions:

In patients with hematologic malignancies, routine LP confirmed the rarity of CNS invasion, irrespective of initial high-risk features. Subsequent routine LPs after initial diagnosis demonstrated utility in identifying false negative CSF studies after prophylactic treatment and in early detection of CNS invasion. Due to the limited sample size, the clinical efficacy of routine LP was not fully elaborated. This ongoing retrospective study aims to analyze over 800 patients, providing a higher-powered study to assess the significance of routine LPs in patients at high risk for CNS involvement.