scholarly journals Efficacy and safety of high-dose etoposide cytarabine as consolidation following rituximab methotrexate temozolomide induction in newly diagnosed primary central nervous system lymphoma in immunocompetent patients

Haematologica ◽  
2018 ◽  
Vol 103 (7) ◽  
pp. e296-e299 ◽  
Author(s):  
Rudy Birsen ◽  
Lise Willems ◽  
Johan Pallud ◽  
Estelle Blanc ◽  
Barbara Burroni ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
High Dose ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Immunocompetent Patients

scholarly journals Challenges in the Treatment of Newly Diagnosed and Recurrent Primary Central Nervous System Lymphoma

2020 ◽  
Vol 18 (11) ◽  
pp. 1571-1578
Author(s):  
Matthias Holdhoff ◽  
Maciej M. Mrugala ◽  
Christian Grommes ◽  
Thomas J. Kaley ◽  
Lode J. Swinnen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Phase Ii Trials ◽  
Whole Brain Radiation ◽  
The Central Nervous System

Primary central nervous system lymphomas (PCNSLs) are rare cancers of the central nervous system (CNS) and are predominantly diffuse large B-cell lymphomas of the activated B-cell (ABC) subtype. They typically present in the sixth and seventh decade of life, with the highest incidence among patients aged >75 years. Although many different regimens have demonstrated efficacy in newly diagnosed and relapsed or refractory PCNSL, there have been few randomized prospective trials, and most recommendations and treatment decisions are based on single-arm phase II trials or even retrospective studies. High-dose methotrexate (HD-MTX; 3–8 g/m2) is the backbone of preferred standard induction regimens. Various effective regimens with different toxicity profiles can be considered that combine other chemotherapies and/or rituximab with HD-MTX, but there is currently no consensus for a single preferred regimen. There is controversy about the role of various consolidation therapies for patients who respond to HD-MTX–based induction therapy. For patients with relapsed or refractory PCNSL who previously experienced response to HD-MTX, repeat treatment with HD-MTX–based therapy can be considered depending on the timing of recurrence. Other more novel and less toxic regimens have been developed that show efficacy in recurrent disease, including ibrutinib, or lenalidomide ± rituximab. There is uniform agreement to delay or avoid whole-brain radiation therapy due to concerns for significant neurotoxicity if a reasonable systemic treatment option exists. This article aims to provide a clinically practical approach to PCNSL, including special considerations for older patients and those with impaired renal function. The benefits and risks of HD-MTX or high-dose chemotherapy with autologous stem cell transplantation versus other, better tolerated strategies are also discussed. In all settings, the preferred treatment is always enrollment in a clinical trial if one is available.

Recurrent genetic alterations in primary central nervous system lymphoma of immunocompetent patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2023-2023
Author(s):  
Alberto Gonzalez ◽  
Ahmed Idbaih ◽  
Blandine Boisselier ◽  
Anne Jouvet ◽  
Marc Polivka ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Somatic Mutations ◽  
Hot Spot ◽  
Quantitative Polymerase Chain Reaction ◽  
Snp Array ◽  
Central Nervous System Lymphoma ◽  
Genetic Alterations ◽  
High Dose ◽  
Immunocompetent Patients

2023 Background: Little is known about the molecular pathogenesis of primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Our objective was to identify the genetic changes involved in PCNSL oncogenesis and evaluate their clinical relevance. Methods: Twenty nine and four newly diagnosed, HIV-negative PCNSL patients were investigated using high-resolution single nucleotide polymorphism (SNPa) arrays (Infinium Illumina Human 610-Quad SNP array-Illumina; validated by real-time quantitative polymerase chain reaction) and whole-exome sequencing respectively. Molecular results were correlated with prognosis. Results: All PCNSLs were diffuse large B-cell lymphomas, and the patients received high-dose methotrexate-based polychemotherapy without radiotherapy as an initial treatment.SNPa analysis revealed recurrent large and focal chromosome imbalances that target candidate genes in PCNSL oncogenesis. The most frequent genomic changes were (i) 6p21.32 loss (79%), corresponding to the HLA locus; (ii) 6q loss (27-37%); (iii) CDKN2A homozygous deletions (45%); (iv) 12q12-q22 (27%); (v) chromosome 7q21 and 7q31 gains (20%). Sequencing of matched tumor and blood DNA samples identified novel somatic mutations in MYD88 (L265P hot spot mutation) and TBL1XR1 in 38% and 14% of the cases, respectively. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis showed that 6q22 loss (p=0.006 and p=0.01), and CDKN2A homozygous deletion (p=0.02 and p=0.01) were significantly associated with shorter progression free survival and overall survival. Conclusions: Our study identified novel genetic alterations in PCNSL, such as MYD88 and TBL1XR1 somatic mutations, which would both contribute to the constitutive activation of the NFkB signaling pathway and represent potential promising targets for future therapeutic strategies.

scholarly journals Efficacy and Safety of Autologous Stem-Cell Transplantation as Part of First-Line Treatment for Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 11 ◽  
Author(s):  
Jing Liu ◽  
Jiayuan Guo ◽  
Xuefei Sun ◽  
Yuanbo Liu ◽  
Chunji Gao
Keyword(s):  
Systematic Review ◽  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Prospective Studies ◽  
Meta Analysis ◽  
Central Nervous System Lymphoma ◽  
Newly Diagnosed ◽  
Efficacy And Safety

ObjectiveThe reviewed literature supports a treatment regimen for primary central nervous system lymphoma (PCNSL) that includes induction chemotherapy, followed by one consolidation therapy. High-dose chemotherapy supported by autologous stem-cell transplantation (ASCT) is the most studied option, but its effects are controversial. The aim of this study was to evaluate the efficacy and safety of ASCT for newly diagnosed PCNSL by means of a meta-analysis.MethodsThe PubMed, Embase, and Cochrane Library databases were systematically searched for studies published until May 20, 2021. Included studies were prospective studies of patients with newly diagnosed PCNSL treated with ASCT. The pooled rates and 95% confidence intervals (CIs) were determined for all outcomes. Subgroup analysis was conducted to compare the relative risk (RR) with 95% CIs for the complete remission (CR) rate and the hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS).ResultsThirteen prospective studies including 348 patients were analyzed. The pooled CR rate, overall response rate, and relapse rate were 80% (95% CI, 71–88%, I2 = 67.06%, p = 0.00), 95% (95% CI, 87–100%, I2 = 73.65%, p= 0.00), and 19% (95% CI, 15–24%, I2 = 76.18%, p = 0.00), respectively. The pooled 2- and 5-year PFS and OS rates were 74% (95% CI, 68–80%, I2 = 3.90%), 65% (95% CI, 51–77%, I2 = 74.61%), 80% (95% CI, 72–88%, I2 = 57.54%), and 69% (95% CI, 53–83%, I2 = 83.89%), respectively. Hematological toxicity and infections were more common adverse events above grade 3. The pooled treatment-related mortality was 3% (95% CI, 1–6%, I2 = 28.18%, p = 0.16). In the group analysis of ASCT compared with whole-brain radiotherapy, there were no significant differences in the CR rate (RR, 1.00, 95% CI, 0.88–1.14, p = 0.971), relapse rate (RR, 0.44, 95% CI, 0.06–3.10, p = 0.408), PFS (HR, 1.28, 95% CI, 0.81–2.01, p = 0.29), or OS (HR, 1.62, 95% CI, 0.97–2.69, p = 0.06). Cognitive functions were preserved or improved after ASCT.ConclusionsASCT is a feasible approach for consolidation with good tolerability for newly diagnosed PCNSL patients. High-quality randomized controlled trials are still needed to confirm the effects of ASCT.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021268422.

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