Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B‐cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance

Wight, Joel; Yue, Mimi; Keane, Colm; Johnston, Anna; Linton, Kim; Chin, Collin K.; Wai, Shin Hnin; Talaulikar, Dipti; Gasiorowski, Robin; Cheah, Chan Yoon; Gregory, Gareth P.; Dickinson, Michael; Minson, Adrian; Coombes, Caitlin; Ku, Matthew; Lam, Stephanie; Hawkes, Eliza A

doi:10.1111/bjh.16064

Cited by 25 publications

(32 citation statements)

References 30 publications

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“…For the 50 patients with DLBCL or HGBCL with synchronous CNS and systemic involvement at diagnosis, the 2-year PFS of 43% and OS of 57% reported in our study are in line with outcomes reported in similar retrospective studies showing 2-3-year PFS and OS of 42-45% and 44-56%, respectively. 37,[39][40][41] Improved outcomes have been reported with the use of more intensive first-line chemotherapy options, with or without consolidative autologous stem cell transplantation, in non-randomized clinical trials that included small numbers of patients with DLBCL or HGBCL with synchronous CNS and systemic involvement at diagnosis. 10,42 In addition to its single-center retrospective nature, our study has several limitations.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

Fleming¹,

Huang

Dotson³

et al. 2022

Blood Advances

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The optimal timing for administering high-dose methotrexate (HDMTX) when combined with (R)CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, with/without rituximab) is unclear. Recent data showed that the administration of prophylactic HDMTX before day 10 of R-CHOP may lead to fewer treatment delays. Herein, we report our experience with HDMTX administered on day 1 of (R)CHOP in patients with aggressive non-Hodgkin lymphoma. We identified 140 patients treated with ≥1 cycle of HDMTX combined with (R)CHOP for prophylaxis against (n=84) or treatment of (n=56) central nervous system involvement. Overall, (R)CHOP treatment delays ≥7 days (4% of cycles, 13% of patients), doxorubicin and/or cyclophosphamide dose reductions (1% of cycles, 6% of patients) or (R)CHOP discontinuations due to toxicity (4% of patients) were uncommon. Neutropenic fever (NF) occurred in 7% of cycles and 24% of patients and was more common during HDMTX-containing cycles. Acute kidney injury (AKI) occurred in 19% of cycles but was mostly grade ≤2. Grade ≥3 hepatotoxicity and mucositis were uncommon (each 2% of cycles). In the prophylaxis cohort, the rates of NF and grade ≥2 AKI were lower in patients who initiated HDMTX with cycle 2 or later (11% vs 30%, p=0.03 and 16% vs 39%, p=0.03, respectively). Our data show that HDMTX administration on day 1 of (R)CHOP may improve the deliverability of (R)CHOP and the overall safety of the regimen compared with historical data of HDMTX administration on day 10 or later of R-CHOP. Delaying prophylactic HDMTX beyond cycle 1 of (R)CHOP may reduce the risk of NF and AKI.

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Section: Discussionmentioning

confidence: 99%

Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

Fleming¹,

Huang

Dotson³

et al. 2022

Blood Advances

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“…Data on optimal treatment for patients with secondary CNS involvement at initial presentation are even scarcer [10, 21, 22]. Available retrospective analysis underlines the role of intensive CNS-directed chemotherapy for controlling CNS manifestation of lymphoma in these patients [23, 24]. However, the value of consolidating ASCT in this patient cohort is not well defined.…”

Section: Discussionmentioning

confidence: 99%

“…However, the value of consolidating ASCT in this patient cohort is not well defined. Damaj et al [23] retrospectively reported a significant survival benefit for patients receiving a consolidative ASCT (19 of 60 patients receiving ASCT with a 3-year overall survival of 75% compared to 29%), whereas Wight et al [24] could not observe a significant difference for consolidative ASCT in patients treated with intensive CNS-directed therapy when matched for induction outcomes (38 of 80 patients receiving intensive CNS induction therapy, of which 14 received ASCT with a nonsignificant 2-year overall survival of 66% compared to 56%).…”

Section: Discussionmentioning

confidence: 99%

Outcome of a Real-World Patient Cohort with Secondary CNS Lymphoma Treated with High-Intensity Chemoimmunotherapy and Autologous Stem Cell Transplantation

et al. 2021

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Background: Aggressive non-Hodgkin lymphomas with secondary central nervous system (CNS) involvement bear a dismal prognosis. Optimal treatment remains so far unclear, and effective treatment options remain an unmet clinical need. Remission rates are in general low, resulting in rapid relapses and palliative care in the majority of patients. High-intensity treatment combining effective CNS-directed chemoimmunotherapy with autologous stem cell transplantation was shown in a recent phase 2 trial to induce durable remissions. Here, we report the outcome of the first real-world patient cohort treated according to the published protocol. Methods: We retrospectively identified 17 HIV-negative lymphoma patients with secondary CNS involvement, either at first diagnosis or at relapse of lymphoma, treated according to the study protocol published by Ferreri et al. [J Clin Oncol. 2015] at two university medical centers in Germany. Treatment consisted of four cycles of chemoimmunotherapy with a consolidating autologous stem cell transplantation. Adverse events and overall outcome were assessed. Results: Five patients had CNS involvement at first diagnosis and 12 patients at relapse of lymphoma. A complete response was achieved in 9 patients. Median survival was 11 months. Five patients died of septic complications and 4 patients succumbed to progression or relapse of disease. Conclusions: The outcome of our real-world cohort emphasizes the possible toxic character of the treatment protocol by Ferreri et al. [J Clin Oncol. 2015]. Further improvement in treatment regimens is still an unmet need.

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“…Therefore, the study of genes and signal pathways regulated during tumorigenesis will contribute to the study of the pathological mechanism of DLBC and guide the therapeutic effect [ 2 , 3 ]. It usually occurs only outside the central nervous system or is less isolated from the central nervous system [ 4 ]. It is very aggressive and progresses rapidly, so early treatment is the critical way to save the lives of DLBC patients.…”

Section: Introductionmentioning

confidence: 99%

Hub Gene and Its Key Effects on Diffuse Large B-Cell Lymphoma by Weighted Gene Coexpression Network Analysis

2021

BioMed Research International

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Diffuse large B-cell lymphoma (DLBC) is a kind of tumor with rapid progress and poor prognosis. Therefore, it is necessary to explore new biomarkers or therapeutic targets to assist in diagnosis or treatment. This study is aimed at screening hub genes by weighted gene coexpression network analysis (WGCNA) and exploring the significance of overall survival (OS) in DLBC patients. Statistical data using WGCNA to analyze mRNA expression in DLBC patients came from The Cancer Genome Atlas (TCGA) dataset. After analyzing with clinical information, the biological functions of hub genes were detected. Survival analysis, Cox regression detection, and correlation analysis of the hub genes were carried out. The potential function of the hub gene related to prognosis was predicted by gene set enrichment analysis (GSEA). The results showed that APOE, CTSD, LGALS2, and TMEM176B expression in normal tissues was significantly higher than that in cancer tissues ( P < 0.01 ). Survival analysis showed that patients with high APOE and CTSD were associated with better OS ( P < 0.01 ). APOE and CTSD genes were mainly enriched in the regulation of ROS and oxidative stress. The two hub genes related to the prognosis of DLBC were identified and verified based on WGCNA. Survival analysis showed that the overexpression of APOE and CTSD in DLBC might be beneficial to the prognosis. These findings identified vital pathways and genes that may become new therapeutic targets and contribute to prognostic indicators.

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Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B‐cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance

Cited by 25 publications

References 30 publications

Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

Outcome of a Real-World Patient Cohort with Secondary CNS Lymphoma Treated with High-Intensity Chemoimmunotherapy and Autologous Stem Cell Transplantation

Hub Gene and Its Key Effects on Diffuse Large B-Cell Lymphoma by Weighted Gene Coexpression Network Analysis

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