Methotrexate-induced chemical meningitis in patients with acute lymphoblastic leukemia/lymphoma
Linu A Jacob1, Aparna Sreevatsa1, Lakshmaiah K Chinnagiriyappa1
1Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India.
Background:
Intrathecal methotrexate (ITMTX) is an important component in the treatment as well as prophylaxis of leukemia/lymphoma. ITMTX can cause chemical meningitis characterized by vomiting, headache, and fever lasting 2-5 days with spontaneous resolution of symptoms which differentiates this syndrome from bacterial meningitis.
Objective:
This prospective observational study was carried out to determine incidence of post-ITMTX syndrome in patients receiving prophylactic ITMTX as part of Berlin-Frankfurt-Munster (BFM) protocol.
Materials And Methods:
Patients aged 15-50 years receiving BFM 90 or BFM 95 protocol for acute lymphoblastic leukemia or lymphoblastic lymphoma were followed up for post-ITMTX syndrome, defined as vomiting, headache and fever between 38° and 39°C following ITMTX.
Results:
Thirty-three patients received a total of 297 courses of ITMTX. Of the 297 doses of ITMTX, 20 episodes (6.7%) of post-ITMTX syndrome were observed. The incidence of post-ITMTX syndrome was highest after the second dose of ITMTX (24%). The most common symptom of post-ITMTX syndrome was headache which was seen in 17 (85%) patients. Seventeen (85%) patients had vomiting, 10 (50%) patients had fever, and 4 (20%) patients had backache. Meningeal signs were present in 2 (10%) patients.
Conclusions:
Post-ITMTX syndrome is not uncommon in adult patients receiving prophylactic ITMTX for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Patients develop a toxic syndrome closely mimicking acute bacterial meningitis but spontaneous recovery is seen without any neurological sequelae.
Insights
Post-ITMTX syndrome, a chemical meningitis, occurs in 6.7% of adult patients receiving prophylactic intrathecal methotrexate (ITMTX) for leukemia/lymphoma. Symptoms like headache and vomiting resolve spontaneously without lasting effects.
Area of Science:
- Oncology
- Pharmacology
- Neurology
Background:
- Intrathecal methotrexate (ITMTX) is crucial for leukemia/lymphoma treatment and prophylaxis.
- ITMTX can induce chemical meningitis with symptoms like headache, vomiting, and fever, distinct from bacterial meningitis.
Purpose of the Study:
- To determine the incidence of post-ITMTX syndrome in adult patients receiving prophylactic ITMTX.
- To analyze the clinical presentation and characteristics of this syndrome within the BFM protocol framework.
Main Methods:
- Prospective observational study involving adult patients (15-50 years) undergoing BFM 90 or BFM 95 protocols.
- Monitoring for post-ITMTX syndrome, defined by specific symptoms and temperature, following ITMTX administration.
Main Results:
- A total of 297 ITMTX courses were administered to 33 patients, with 20 episodes (6.7%) of post-ITMTX syndrome observed.
- Headache (85%) and vomiting (85%) were the most frequent symptoms. The highest incidence (24%) occurred after the second ITMTX dose.
- Fever (50%) and backache (20%) were also noted, with meningeal signs in 10% of patients.
Conclusions:
- Post-ITMTX syndrome is a recognized complication in adult patients receiving prophylactic ITMTX for acute lymphoblastic leukemia and lymphoblastic lymphoma.
- The syndrome mimics bacterial meningitis but is characterized by spontaneous recovery without neurological sequelae.
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