Impact of Central Nervous System International Prognostic Index on the Treatment of Diffuse Large B Cell Lymphoma

Ma’koseh, Mohammad; Tamimi, Faris; Abufara, Alaa; Abusalem, Lana; Salama, Osama; Saleh, Yacob; Khader, Rnad; Faiyoumi, Baha A; Al-Rwashdeh, Mohammad; Halahleh, Khaled

doi:10.7759/cureus.16802

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…В то же время примерно у 70-80 % больных, отнесенных к группе высокого риска, которым обязательно проводится терапия с целью профилактики, рецидивы не возникают, что приводит к чрезмерному лечению этих пациентов. Поэтому так важно вести поиск дополнительных предикторов развития рецидива ДВККЛ в ЦНС для возможного их учета совместно с существующей прогностической мо делью [6,7].…”

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Mutation profile of diffuse large B-cell lymphoma with relapses in the central nervous system

et al. 2022

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Introduction. The recurrence of diffuse large B-cell cell lymphoma in the central nervous system in the vast majority of cases is a fatal manifestation of the disease. The study of the lymphoma mutational profile can improve the accuracy of the prognosis of relapse in the central nervous system and justify the selection of patients for preventive treatment. Aim. To evaluate the mutational profile of cases of diffuse large B-cell cell lymphoma with central nervous system damage in relapse based on the results of our own experiment on high-performance sequencing.Materials and methods. On the Illumina platform, full-exome sequencing of diagnostic samples of diffuse large B-cell cell lymphoma with relapses in the central nervous system was performed. A panel including more than 70 genes was analyzed.Results. Four main groups of genetic events can be distinguished in the group of studied samples, namely: combined mutations in the NF-kB (MYD88, NOTCH1, CD79B, CARD11) and JAK-STAT (PIM1, STAT6) signaling pathways, as well as aberrations in the main oncosuppressor TP53 and chromatin remodeling system genes (ARID1A, KMT2D, EP300, SMARCA4). A recurrent mutation c. 794T>C, p.L265P MYD88 was detected in the study group. Among other findings, mutations in the CIITA and CD58 genes should be noted, which are important in avoiding tumor cells from immune surveillance.Conclusion. Despite the apparent heterogeneity of the mutational profile of diffuse large B-cell cell lymphoma with relapses in the central nervous system, in most cases, tumor cells were characterized by genetic disorders leading to the production of a large number of pro-inflammatory cytokines by malignant lymphocytes, as well as aberrations that reduce immunogenicity and contribute to the avoidance of immune surveillance by the tumor.

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Section: Introductionunclassified

Mutation profile of diffuse large B-cell lymphoma with relapses in the central nervous system

et al. 2022

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Оптимизация Терапии У Пациентов С Впервые Диагностированной Диффузной В-Крупноклеточной Лимфомой: Эффективность И Безопасность Программы R-Sd-Epoch ± HDMTX В Рамках Одноцентрового Нерандомизированного Проспективного Клинического Исследования (Предварительные Результаты)

Мингалимов,

Барях,

Мисюрина

et al. 2024

Clinical Oncohematology

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Aim. To assess clinical efficacy and safety of the intensified program R-SD-EPOCH ± HDMTX (R-split-dose-EPOCH ± high-dose MTX) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials & Methods. From October 2022 to August 2023, 25 newly diagnosed DLBCL patients were enrolled into the trial protocol. Data of 23 patients were analyzed. The age of patients was 46–70 years (median 63 years); there were 13 women and 10 men. Stage II with bulky tumor lesion was registered in 7 patients; 16 patients showed advanced stages (III and IV). The IPI stratification yielded 13 high-risk, 7 intermediate-high risk, and 3 intermediate-low risk patients. In accordance with the CNS-IPI criteria, 14 patients were listed as high-risk. All 23 patients were treated with R-SD-EPOCH (rituximab, prednisolone, and cyclophosphamide; etoposide, vincristine, and doxorubicin were administered in fractionated doses). High-dose methotrexate as part of R-SD-EPOCH (continuous 3 g/m2 infusion over 12 hours) was administered exclusively to the CNS-IPI high-risk patients. They received it on Day 16 of R-SD-EPOCH ± HDMTX cycles 2, 4, and 6. Results. The methotrexate-free R-SD-EPOCH regimen was administered throughout the whole program to 9 patients, whereas 14 patients received R-SD-EPOCH ± HDMTX (methotrexate was administered only in cycles 2, 4, and 6). Overall response in the whole cohort (n = 23) was 95 %. Interim PET-CTs were performed after chemotherapy cycles 2 and 4 in 21 patients. Complete metabolic response was achieved in 20 (95 %) patients, whereas partial metabolic response was registered in 1 (5 %) patient. One of the remaining 2 patients was undergoing initial treatment by the time of analysis. The other one with partial response assessed by contrast-enhanced CT, died after surgery for colon perforation followed by localized peritonitis. The patients in the present trial showed equal 10-month PFS and OS rates of 85 % (median not reached; 95% CI 66.4–100.0 %). Hematologic toxicity grade 3/4 was identified in 14 (60 %) patients, and non-hematologic toxicity was observed in 9 (35 %) patients. Conclusion. The preliminary results of the present clinical trial of the intensified program R-SD-EPOCH ± HDMTX as the first method for the drug treatment of DLBCL demonstrate high efficacy and acceptable safety profile. The data obtained point towards the feasibility of continuing this clinical trial.

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Impact of Central Nervous System International Prognostic Index on the Treatment of Diffuse Large B Cell Lymphoma

Cited by 2 publications

References 29 publications

Mutation profile of diffuse large B-cell lymphoma with relapses in the central nervous system

Mutation profile of diffuse large B-cell lymphoma with relapses in the central nervous system

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