Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors

Bessell, E.M.; Graus, Francesc; López‐Guillermo, Armando; Lewis, Sarah; Villà, Salvador; Verger, E.; Petit, J

doi:10.1016/j.ijrobp.2003.11.001

Cited by 97 publications

(67 citation statements)

References 31 publications

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“…The addition of various other drugs such as cytarabine, ifosfamide and high-dose chemotherapy with subsequent stem cell support has been assessed or is under clinical investigation (1, 2). Higher age and reduced performance status have repeatedly been described as prognostic factors associated with shorter survival (3)(4)(5). The definition of additional prognostic factors might be helpful to define patient populations that require an even more intense or prolonged therapy to delay tumor recurrence and unfavourable outcome.…”

Section: Introductionmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3months and was compared to 20 LTS patients with a median OS of 55months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Here we characterized microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analyzed by next generation sequencing.The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS.Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal AUC above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time PCR in a validation cohort consisting of 20 STS and LTS patients.In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.

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Section: Introductionmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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“…12,13 Although PCNSL prognosis has improved the most over the past decade, it remains poor, with a 5-year overall survival (OS) rate of approximately 30% for the patients benefiting from the best treatment protocols. [14][15][16][17] It is still unclear whether the poor outcome is attributable to the specific cerebral location or reflects an exceptionally aggressive biologic behavior of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

A uniform activated B-cell–like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases

Camilleri-Broët¹,

Crinière²,

Broët³

et al. 2005

Blood

332

226

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“…Median survival is 17-45 months in immunocompetent patients, and only 13.5 months in those with AIDS. 7 Although several clinical factors, including age, performance status, and extent of disease, have been found to be prognostically significant in some studies, 8,9 a validated method of predicting prognosis in these patients remains to be elucidated.…”

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confidence: 99%

Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases

et al. 2010

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Primary central nervous system lymphomas are rare neoplasms characterized by a dismal prognosis relative to other extranodal lymphomas. Approximately 98% of primary central nervous system lymphomas are of B-cell origin, and most belong to the diffuse large B-cell type. Recently, diffuse large B-cell lymphomas have been subcategorized into germinal center and nongerminal center types based on gene expression profiles and immunohistochemical expression of CD10, Bcl-6, and MUM1. Studies have shown that the overall survival rate of the germinal center group is better than that of the nongerminal center lymphomas. In this study, 31 cases of primary central nervous system lymphomas of the diffuse large B-cell type were retrieved, reviewed, and immunostained for CD10, Bcl-6, MUM1, and Ki-67. Subclassification was carried out as described earlier, where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered characteristic of germinal center subtype and the opposite expression of nongerminal center subtype. Furthermore, the proliferative activity was semiquantitatively assessed using percent positive cells staining with Ki-67. Of the 31 cases examined, 26 (84%) were found to belong to the nongerminal center type. The Ki-67 index in these 26 cases ranged from 30 to 90% (mean, 69%). Five cases were categorized as the germinal center subtype. They had an Ki-67 index between 70 and 90% (mean, 78%). Interestingly, none of our patients were known to be HIV positive. One patient had a 10-year history of orthotopic liver transplant. We also performed fluorescence in situ hybridization analysis on formalin-fixed material and found that 38% of the cases where tissue was available had abnormalities of MYC/ IGH and/or IGH/BCL2. We conclude that most primary central nervous system diffuse large B-cell lymphomas are of the nongerminal center origin. Regardless of the germinal center status, all cases showed a high proliferative rate. A statistically significant difference in the overall survival between the two groups was not seen.

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Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors

Cited by 97 publications

References 31 publications

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

A uniform activated B-cell–like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases

Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases

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