As many as one-third of patients with temozolomide-induced aplastic anemia (TIAA) may not achieve hematologic recovery (HR), and a lack of recovery is associated with an increased risk of complications and death, according to research published in Neuro-Oncology.
The researchers noted that TIAA is a rare but potentially fatal complication of temozolomide (TMZ) treatment in patients with central nervous system (CNS) malignancies, but the overall prognosis of TIAA is unclear.
The team conducted a 22-year observational cohort study to characterize the presentation, outcomes, complications, and prognosis of TIAA.
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The researchers identified 3821 patients with CNS malignancies who received TMZ. Of these, 34 patients (0.89%) met the criteria for TIAA and were included in the primary analysis.
The patients had glioblastoma (n=20), anaplastic astrocytoma (n=7), anaplastic oligoastrocytoma (n=1), primary CNS lymphoma (n=3), and other CNS tumors (n=3). The patients’ mean age was 60.7 years, 64.7% were women, and all were White.
Most patients (85.3%) developed TIAA before completing a second TMZ cycle. The median time from the start of TMZ treatment to TIAA was 41 days (range, 31.5-49 days).
A total of 23 patients (67.6%) achieved HR, 6 with partial HR and 17 with complete HR. No significant differences in HR were observed between patients who had glioblastoma (65.0%) or non-glioblastoma CNS tumors (71.4%; P =.73).
Compared with patients who had HR, patients without HR had an increased risk of complications, including:
- Febrile neutropenia — 72.7% in patients without HR and 30.4% in patients with HR (P =.02)
- Infectious complications — 45.5% and 8.7%, respectively (P =.01)
- Hospitalization — 81.8% and 43.5%, respectively (P =.04)
- Death — 100% and 60.9%, respectively (P =.02).
The median overall survival from TIAA diagnosis was 355 days for the entire cohort. It was 1414 days for patients with complete HR, 752 days in patients with partial HR, and 28 days in patients without HR (P <.0001).
There were 29 patients (85.3%) who received at least 1 type of hematopoietic growth factor support. The rate of HR was similar between patients who received granulocyte colony-stimulating factor (G-CSF) and those who did not — 68.0% and 66.7%, respectively (P =.99).
The rate of HR was numerically, but not significantly, higher in patients who received thrombopoietin receptor agonists (TPO-RAs) compared with patients who did not — 81.8% and 60.9%, respectively (P =.15). Of the patients who received both G-CSF and a TPO-RA, 85.7% achieved HR.
“Given our observations, the low potential for harm of TPO-RAs and the high morbidity and mortality of TIAA, the early and aggressive use of TPO-RAs in patients with TIAA, similar to the approach used in classical autoimmune aplastic anemia, appears appropriate,” the researchers wrote. “Additional study is needed to understand risk factors for TIAA and develop effective treatment regimens for this challenging complication of TMZ chemotherapy.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Park AK, Waheed A, Forst DA, Al-Samkari H. Characterization and prognosis of temozolomide-induced aplastic anemia in patients with central nervous system malignancies. Neuro Oncol. Published online October 14, 2021. doi:10.1093/neuonc/noab240
