RESUMO
The median survival time of patients with glioblastoma is 14-16 months with a 5-year overall survival rate of 9.8%. Standard of care treatment includes radiation with concomitant temozolomide followed by cyclic temozolomide. If the patient develops myelosuppression (thrombocytopenia, leukopenia or anemia), the dose of temozolomide is reduced or stopped to avoid bleeding or infections. Recent studies have demonstrated that mild leukopenia is associated with increased overall survival in patients with glioblastoma. To confirm prior results showing that leukopenia is associated with increased overall survival as a primary outcome in patients with glioblastoma, the present study retrospectively collected complete blood counts from 141 patients with glioblastoma treated at the Beth Israel Deaconess Medical Center (Boston, USA) between January 2012 and December 2017. According to Kaplan-Meier analysis with a log-rank test, the presence of leukopenia was associated with increased overall survival (P=0.008). Furthermore, patients with grade 2 leukopenia (Common Terminology Criteria for Adverse Events version 5.0) survived longer than those without myelosuppression (P=0.024). There was no difference in overall survival between patients with grade 1, 3 or 4 leukopenia and those without myelosuppression. Leukopenia was associated with longer survival independent of age or extent of surgery in Cox proportional hazards regression modeling (P=0.00205). A possible interpretation is that grade 2 leukopenia is a biomarker of adequate temozolomide dosing in a population with diverse DNA repair function, which may be the consequence of variable O6-methylguanine-DNA methyltransferase activity. A prospective dose escalation trial is necessary to determine if treatment-induced leukopenia is beneficial for all patients receiving temozolomide.
RESUMO
PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive variant of non-Hodgkin lymphoma. The diagnostic gold standard remains the pathologic review of tumor tissue mainly collected though biopsies. The majority of PCNSL are diffuse large B cell lymphoma (DLBCL). Biopsies are invasive procedures, and there have been efforts to develop minimally invasive diagnostic testing using serum and cerebral spinal fluid. This article reviews multiple markers that could potentially serve as future diagnostic tools and predictors of treatment response. RECENT FINDINGS: Many studies have attempted to classify DLBCL into different subtypes for prognostic purposes using methods such as immunohistochemistry. PCNSL often falls under the activated B-cell-like subgroup, and further genomic sequencing has identified alterations in genes within the B-cell receptor signaling axis at increased frequencies. Two such genes, MYD88 and CD79B, implicate the involvement of the NF-kB (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, and targeted agents to this pathway are currently being used in the treatment of relapsed/refractory PCNSL. SUMMARY: Although recent genomic profiling of PCNSL has increased the understanding of drivers in this disease and has also led to the introduction of targeted inhibitors, these markers have not yet been used for diagnostic and/or prognostic purposes. Further studies will need to evaluate if they hold great diagnostic potential.
