Intrathecal Methotrexate Effective In CSF Clearance, Improving Neurologic Symptoms In AML Patients With CNS Involvement
In a multi-institutional investigation, researchers found that intrathecal (IT) methotrexate therapy showed efficacy in cerebral spine fluid (CSF) clearance and improving neurologic symptoms in patients with acute myeloid leukemia with central nervous system involvement (CNS AML).1
Central nervous system involvement is an uncommon manifestation of AML. One study found that CNS involvement in less than 1% of more than 3000 adults who were newly diagnosed with AML.2 With few guidelines for screening and treatment, research on this population has stalled. Enter Sastow et al, who retrospectively identified patients with CNS AML and evaluated several treatments and outcomes for this type of cancer at two large academic institutions, Mount Sinai Hospital and the University of Kansas Medical Center.
The researchers defined CNS AML as “the presence of leukemic blasts in the cerebral spinal fluid (CSF) or atypical immature myeloid cells in the CSF with either suspicious imaging findings and/or neurologic symptoms.” To determine survival analysis, Sastow et al used the Kaplan-Meier method. For additional analyses, the authors used descriptive statistics.
The researchers identified a total of 52 adult patients with features associated with CNS AML including monocytic differentiation (40%), elevated lactate dehydrogenase (67%), white blood cells greater than 100K (37%), and FLT3 mutation (46%). Neurologic symptoms were reported in most patients (n = 36), with headache as the most common (33%). Vision changes (25%) and radicular pain (10%) were also noted.
For their study, 90% of patients received at least one dose of IT methotrexate, while 71% received at least one dose of IT cytarabine. Additionally, 65% of patients had at least one dose of both. The median number of IT doses received was four (range 0-31).
According to the results of their analysis, 84% of patients achieved CSF clearance, with a median number of IT doses required for clearance of one (range 1-9). Of these patients with CSF clearance, 21% had a relapse with 67% of those having concurrent bone marrow relapse.
Of the 36 patients with baseline neurologic symptoms, 69% had improvement in symptoms post-IT therapy. Sastow et al also found that the median overall survival was 9.3 months for patients with CNS involvement diagnosed before or during induction and 3.5 months for those diagnosed after induction.
“IT therapy was shown to be rapidly effective in clearing CSF blasts and improving neurologic symptoms in most patients,” the researchers concluded. “Few patients experienced CSF relapse which typically occurred with concomitant bone marrow relapse.”
The authors noted that prospective studies with larger multi-institutional collaborations are still needed to determine the best surveillance and treatment options for CNS involvement in AML.
References:
1. Sastow D, Tatarian J, Kesh YR, et al. A multi‑institutional analysis of outcomes in acute myeloid leukemia patients with central nervous system involvement. Clin Lymphoma Myeloma Leuk. 2023;23(supp 1):S275-S276.
2. Assaad M, Kumar V, Carmack A, Karki A, Golden D. Acute myeloid leukemia with central nervous system involvement following routine surgical procedures: a bridge between surgical, medical, and neurological critical care. Cureus. 2022;14(1):e21245. doi:10.7759/cureus.21245.