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Abstract: Diffuse large B-cell lymphoma (DLBCL) has variable prognosis, with only 50 to 60% of patients cured by standard first line treatment. Identifying patients unlikely to benefit from standard first line therapy is therefore crucial. Schmitz’s study identified four molecular subtypes of DLBCL with differing prognoses: MCD, BN2, N1, and EZB, with BN2 and EZB showing more favorable outcomes. This study aimed to evaluate the effectiveness of the Archer FusionPlex Lymphoma Assay in identifying the newly defined genetic subtypes of DLBCL, while also exploring the association between immunohistochemical (IHC) and next-generation sequencing (NGS) methods for classifying the cell of origin (COO) and assessing their predictive value for patient survival. Materials and methods. We classified 131 DLBCL patients using Hans algorithm into GCB (germinal center B-celllike) and ABC (activated B-cell-like) subtypes, and with NGS applying Archer FusionPlex lymphoma assay into ABC, GCB, unclassified, and into Schmitz’s novel genetic subtypes. A mutational analysis of just 7 genes (MYD88L265P, CD79B, EZH2, NOTCH1, NOTCH2, BCL2, and BCL6) was used for genetic classification. Various statistical models were applied to assess survival differences between subtypes. Finally, STRATOS analysis was conducted to validate our preliminary statistical findings. Results. 35.9% of patients were successfully classified into new genetic subtypes, with acceptable consistency between IHC and NGS method for COO determination. However, the new genetic subtype classification by NGS did not correlate with overall survival, nor did the COO classifications by IHC or NGS. The inclusion of these classifications also did not improve the predictive value of models compared to the basic model based on the International Prognostic Index (IPI) only. Conclusions. The Archer FusionPlex Lymphoma assay showed a somewhat lower detection rate of novel genetic subtypes compared to reports based on exome sequencing, yet identified novel genetic subtypes in over one-third of patients. However, an in-depth STRATOS statistical analysis did not confirm its predictive value for DLBCL prognosis, likely due to factors like patient selection and sample size limitations.
Keywords: diffuse large B-cell lymphoma, new genetic types, prognostic factors
Published in DiRROS: 26.11.2025; Views: 293; Downloads: 68
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Abstract: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are not cured with first-line chemoimmunotherapy, resulting in poor prognosis. Schmitz et al. classified DLBCL into four prognostic genetic groups using whole-exome sequencing. We applied a simplified approach using a targeted next-generation sequencing assay (Archer FusionPlex Lymphoma Assay) to analyze samples from 105 patients—53 with a progression-free survival (PFS) < 2 years (the “Relapse group”) and 52 with a PFS > 5 years (the “Remission group”) following first-line systemic treatment. Patients were classified according to Schmitz et al. into the following categories: “MCD” (MYD88L265P and CD79B alteration), “N1” (NOTCH1 alteration), “BN2” (NOTCH2 alteration and BCL6 translocation), and “EZB” (EZH2 alteration and BCL2 translocation). The predictive value of this simplified genetic classification and of relevant clinical features were evaluated. The “Relapse group” included more patients classified as MCD and N1, while fewer were classified as EZB and BN2. Also, cell-of-origin (COO) characteristics and the size of N1 aligned with the classification of Schmitz et al. However, the limited sample size precludes definitive conclusions about the predictive value of our simplified approach. Additionally, male sex, B symptoms, and bone marrow involvement were associated with relapse. Therefore, these clinical features may be useful in predicting outcomes until an effective molecular classification is widely adopted.
Keywords: DLBCL, genetic classification, predictive, lymphoma
Published in DiRROS: 21.11.2025; Views: 181; Downloads: 52
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Abstract: Background: This study assessed the prognostic value of tumor burden in bone marrow (BM) and total disease (TD), as depicted on 18F-FDG PET/CT in 140 DLBCL patients, for complete remission after first-line systemic treatment (iCR) and 3- and 5-year overall survival (OS3 and OS5). Methods: Baseline 18F-FDG PET/CT scans of 140 DLBCL patients were segmented to quantify metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax in BMI, findings elsewhere (XL), and TD. Results: Bone marrow involvement (BMI) presented in 35 (25%) patients. Median follow-up time was 47 months; 79 patients (56%) achieved iCR. iCR was significantly associated with TD MTV, XL MTV, BM PET positivity, and International Prognostic Index (IPI). OS3 was significantly worse with TD MTV, XL MTV, IPI, and age. OS5 was significantly associated with IPI, but not with MTVs and TLGs. Univariate factors predicting OS3 were XL MTV (hazard ratio [HR] = 1.29), BMI SUVmax (HR = 0.56), and IPI (HR = 1.92). By multivariate analysis, higher IPI (HR = 2.26) and BMI SUVmax (HR = 0.91) were significant independent predictors for OS3. BMI SUVmax resulted in a negative coefficient and hence indicated a protective effect. Conclusions: Baseline 18F-FDG PET/CT MTV is significantly associated with survival. BMI identified on 18F-FDG PET/CT allows appropriate treatment that may improve survival.
Keywords: bone marrow, diffuse large B-cell lymphoma, survival
Published in DiRROS: 09.01.2025; Views: 831; Downloads: 506
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Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. The expression of CD56 in DLBCL is highly unusual. Little is known about its incidence and clinical importance. So far, no genetic profiling was performed in CD56 positive DLBCL.Patients and methods. Tissue microarrays have been constructed, sectioned, and stained by H&E and immuno-histochemistry for 229 patients with DLBCL diagnosed 2008–2017. For CD56 positive cases, clinical data was collected including age at diagnosis, stage of the disease, International Prognostic Index (IPI) score, treatment scheme and number of chemotherapy cycles, radiation therapy, treatment outcome, and possible relapse of the disease. Overall survival (OS) and progression-free survival (PFS) were calculated. For four patients, RNA was extracted and targeted RNA (cDNA) sequencing of 125 genes was performed with the Archer FusionPlex Lymphoma kit.Results. CD56 expression was found in 7 cases (3%). The intensity of expression varied from weak to moderate focal, to very intensive and diffuse. All patients had de novo DLBCL. The median age at the time of diagnosis was 54.5 years. Five of them were women and 2 males. According to the Hans algorithm, 6 patients had the germinal centre B cells (GBC) type and one non-GBC (activated B-cell [ABC]) type, double expressor. Genetic profiling of four patients ac-cording to Schmitz’s classification showed that 1 case was of the BN2 subtype, 1 of EZB subtype, 2 were unclassified. The six treated patients reached a complete response and did not experience progression of the disease during the median follow-up period of 80.5 months.Conclusions. We report on one of the largest series of CD56+DLBCL with detailed clinicopathological data and for the first time described genetical findings in a limited number of patients. Our results show that CD56 expression is rare, but seems to be present in prognostic favourable subtypes of DLBCL not otherwise specified (NOS) as tested by immunohistochemical or genetic profiling
Keywords: diffuse large B-cell lymphoma, immunohistochemistry, lymphomas, CD56
Published in DiRROS: 25.07.2024; Views: 1013; Downloads: 371
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Abstract: Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. Case report. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. Conclusions. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance.
Keywords: toxoplasmosis, cerebral, lymphoma, rituximab
Published in DiRROS: 30.04.2024; Views: 1107; Downloads: 635
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