Clinical relevance of brain MRI changes in primary central nervous system lymphoma after high-dose-chemotherapy and autologous stem cell transplantation.

Primary central nervous system lymphoma (PCNSL) is a potentially curable disease, but affected patients often struggle in everyday life due to disease- and therapy-associated sequelae. High-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is the standard consolidation therapy, replacing whole brain radiation therapy (WBRT) amongst others due to less long-term cognitive decline. Nevertheless, white matter lesions (WML) are common findings in brain MRI after HDC/ASCT, but their clinical significance remains underexplored. Here, we correlate WML and brain atrophy with neuropsychological and quality-of-life evaluations collected post-treatment. We found that a significant part of PNCSL long-term survivors develop a high WML burden after HDC/ASCT, but we fail to associate them with specific patient or therapy characteristics. Intriguingly, even a high WML burden does not seem to affect QoL, basic neurocognition testing or performance status negatively. These results contrast findings in previous neuroimaging studies on healthy and cancer patients.

Case report: Sequential inotuzumab, blinatumomab, and chemotherapy with concurrent donor lymphocyte infusions induce complete remission in relapsed pre-B acute lymphoblastic leukemia.

This case report presents the successful management of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia in a 54-year-old male post-allogeneic hematopoietic cell transplantation. The combinatorial approach of sequential antibody treatment (Inotuzumab [InO] and Blinatumomab [Blina]) combined with three donor lymphocyte infusions (DLI) applications and cytoreductive chemotherapy-induced sustained complete molecular remission as documented at the last follow-up 30 months later. This case highlights the feasibility and potential synergistic efficacy of a Blina/DLI regimen and supports the hypothesis that T-cell engagers could enhance the DLI effect. Furthermore, the co-administration of InO, Blina, DLI, and cytoreductive chemotherapy was proven to be feasible without severe adverse events.

Treatment response of advanced HNSCC towards immune checkpoint inhibition is associated with an activated effector memory T cell phenotype.

Locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. The introduction of PD-1 inhibitors has led to a significant improvement in survival, but only a subpopulation of patients responds to therapy. Current biomarkers cannot reliably identify these patients. The identification of biomarkers for the prediction and monitoring of immunotherapy is therefore of great importance. In this study, we characterized lymphocyte subsets in the peripheral blood of HNSCC patients under PD-1 inhibition. Patients with primary response (n=11) to PD-1 inhibition showed an increase of the CD3+ effector memory (CD3/EM) population and an elevated expression of the activation marker CD69 in CD3+ T cells, particularly in the CD3/EM subpopulation at 3 months when treatment response was assessed. In contrast, patients with primary treatment failure and progressive disease (n=9) despite PD-1 inhibition had lower absolute lymphocyte counts and an increased expression of CTLA-4 in CD3+ T cells at the time of treatment failure compared with baseline, particularly in CD4+ and CD8+ effector memory populations. Our results demonstrate that HNSCC patients' response to immune checkpoint inhibition shows a distinct immune signature in peripheral blood, which could help identify refractory patients earlier. Furthermore, strategies to overcome primary therapy failure by inducing a beneficial T cell phenotype or adding alternative immune checkpoint inhibitors could improve response rates and survival of HNSCC patients.

Relevance of different prognostic scores in primary CNS lymphoma in the era of intensified treatment regimens: A retrospective, multicenter analysis of 174 patients.

OBJECTIVES: Treatment intensification (including consolidative high-dose chemotherapy with autologous stem cell transplantation [HDT-ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. METHODS: We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression-free survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three-factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. RESULTS: Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT-ASCT. Two-year OS and 2-year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p = .003) and 3F score (p < .001), but not the IELSG score (p = .06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C-index [0.71]) outperformed both the MSKCC (C-index [0.64]) and IELSG (C-index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C-index (0.66). CONCLUSION: The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches.

Patient Reported and Clinical Outcomes after High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Primary Central Nervous System Lymphoma.

Primary central nervous system lymphomas (PCNSL) are rare and associated with an adverse prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) improves progression free (PFS) and overall survival (OS) but neurocognition, performance status and quality of life (QoL) in patient-reported outcome (PRO) after HDC/ASCT remains underexplored. Especially elderly patients may insufficiently recover from this demanding therapy. Therefore, this single-center analysis investigated all PCNSL patients who received HDC/ASCT at the University Hospital Tübingen from 2006-2021 (n = 40, median age 60.5 years) in a retrospective manner. The 2-year PFS/OS was 78.7%/77.3%, respectively, without significant differences between the tested age-groups (≤60 vs. >60 years, p = 0.531/p = 0.334). Higher Thiotepa dosage was an independent predictor for better OS (p = 0.018). Additionally, a one-time prospective, cross-sectional analysis after HDC/ASCT in the same cohort was performed (n = 31; median follow-up 45 months). Here, the median ECOG improved by HDC/ASCT from 1 to 0 and mini-mental state examinations revealed unimpaired neurocognitive functioning (median 28 pts.). PRO data collected by EORTC QLQ-C30 showed a good QoL in both age groups with an average global health status (GHS) of 68.82% (≤60y: 64.72%, >60y: 74.14%). Together, our data indicate that HDC/ASCT is an effective therapy with respect to disease control, overall health status and quality of life, irrespective of patient age.