Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Do Double-Expressor High-Grade B-Cell Lymphomas Really Need Intensified Treatment? A Report from the Real-Life Series of High-Grade B-Cell Lymphomas Treated with Different Therapeutic Protocols at the Institute of Oncology Ljubljana.

High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed. Only patients with double-expressor lymphoma (DEL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL) were included. Demographic and clinical parameters were assessed, as well as progression-free survival (PFS) and overall survival (OS). In total, 161 cases out of 309 (161/309; 52,1%) were classified as DEL. Sixteen patients had DHL, MYC/BCL2 rearrangement was observed in eleven patients, and MYC/BCL6 rearrangement was observed in five patients. Five patients were diagnosed with THL. Out of 154 patients (according to inclusion/exclusion criteria) included in further evaluation, one-hundred and thirty-five patients had double-expressor lymphoma (DEL), sixteen patients had DHL, and three patients had THL. In total, 169 patients were treated with R-CHOP, 10 with R-CHOP and intermediate-dose methotrexate, 19 with R-DA-EPOCH, and 16 with other regimens. The median follow-up was 22 months. The 5-year OS for the whole DEL group was 57.1% (95% CI 45.9-68.3%) and the 5-year PFS was 76.5% (95% CI 72.6-80.4%). The log-rank test disclosed no differences in survival between treatment groups (p = 0.712) while the high-risk international prognostic index (IPI) carried a significantly higher risk of death (HR 7.68, 95% CI 2.32-25.49, p = 0.001). The 5-year OS for DHL patients was 32.4% (95% CI 16.6-48.2%) while all three TH patients were deceased or lost to follow-up. Our analyses of real-life data disclose that the R-CHOP protocol with CNS prophylaxis is a successful and curative treatment for a substantial proportion of DEL patients.

Outcomes of patients with double/triple expressor diffuse large B-cell lymphoma (DLBCL) treated with R-DA-EPOCH/R-CHOP: A single-center experience.

In Pakistan 76.4% of all NHLs to be diagnosed as DLBCLs. The survival of R-CHOP is better compared to the DA-REPOCH treatment regimen. A prospective follow-up study was conducted with 113 patients to study the outcomes of treatment. Multivariable cox-proportional hazard model was used to estimate the hazard ratios in patients receiving these treatment regimens considering p-value ≤0.05 significant. The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP. For double/triple expressor lymphoma patients received R-DA-EPOCH. The findings of our study demonstrated that the survival rate in both R-CHOP and R-DA-EPOCH is mostly similar.

More Pronounced Muscle Loss During Immunochemotherapy is Associated with Worse Clinical Outcomes in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma with Unfavorable Features.

INTRODUCTION: Cancer-induced cachexia is associated with poor prognosis in patients with non-Hodgkin lymphoma, but it is unknown how and to what extent curable lymphoma treatments affect the musculoskeletal system. PATIENTS AND METHODS: We retrospectively analyzed 104 newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with unfavorable disease features treated with the R-DA-EPOCH regimen. Psoas muscle area (PMA) measured at L3 vertebra level was compared between staging (pre-therapy) and revision (end of treatment) computerized tomography (CT) scans. RESULTS: Small but significant decline in PMA was observed during the immunochemotherapy period (average loss 5%; P=0.016) with 57.7% of patients experiencing muscle loss. Higher body surface area (OR=17.98 for each m2; P=0.034), number of cycles with dose reduction (OR=2.86 for each cycle; P=0.039) and worse response to therapy (OR=3.09 for each response category; P=0.052) were recognized as independent contributors to the PMA loss in multivariate analysis. One quarter of patients had more pronounced PMA loss (≥21%), which was associated with significantly worse overall and progression-free survival. Both ≥21% PMA loss and non-achieving response to therapy remained independently associated with inferior OS (PMA loss HR=2.98; P=0.016 and achieving response HR=0.04; P<0.001) and PFS (PMA loss HR=3.16; P=0.005 and achieving response HR=0.08; P=0.001) in multivariate analyses. DISCUSSION: Muscle loss occurs in approximately half of newly diagnosed DLBCL patients with unfavorable disease features during R-DA-EPOCH immunochemotherapy. If pronounced, this is associated with worse clinical outcomes irrespectively of achieved response to therapy. Muscle loss seems to be mostly affected by the efficacy and tolerability of the regimen.

Expecting the unexpected - Primary mediastinal large B cell lymphoma presenting as huge lung parenchymal mass.

The first possibility considered in the etiology of large lung masses is neoplastic lesions. The differential diagnoses of these masses include bronchogenic carcinoma, pulmonary sarcoma, primitive neuroectodermal tumor etc. Primary or secondary pulmonary parenchymal lymphomas presenting as large mass is distinctly rare. We share the case of a young lady who presented with a large left lung mass almost entirely replacing the left lung parenchyma, with associated intrathoracic lymphadenopathy. On evaluation she was proved to have primary mediastinal large B-cell lymphoma. Treatment with an aggressive chemotherapy regimen led to complete remission of the parenchymal and nodal disease. The uncommon radiological presentation and the excellent therapeutic response despite huge tumor load merit clinical attention.

Very Early Onset of Therapy-Related Acute Myeloid Leukemia with 11q23 Rearrangement Presenting with Unusual PET Findings after R-DA-EPOCH for Primary Mediastinal Large B-Cell Lymphoma.

BACKGROUND: R-DA-EPOCH is an effective regimen for PMLBCL, which permits the omission of consolidative radiotherapy in the majority of patients. PATIENT: We describe a 27-year-old female patient, who achieved a complete remission after treatment with six cycles of R-DA-EPOCH (up to the final level). At 6 months after the end of treatment, PET/CT revealed an unexpected, diffusely increased 18FDG uptake by the bone marrow. Simultaneously, pancytopenia with monocytosis was observed. RESULT: The patient was diagnosed with therapy-related myelodysplastic syndrome, which rapidly evolved into acute myeloid leukemia (t-MDS/AML) with MLL rearrangements. She achieved a complete remission after induction therapy, received an allogenic transplant and remains disease-free 2 years later. CONCLUSIONS: The extremely early onset of t-MDS/AML, together with the unexpected PET/CT findings make this case unique and highlights the need for the accurate estimation of the possible dose-dependent risk of t-MDS/AML after R-DA-EPOCH in the real-life setting in patients with PMLBCL.

Efficacy of dose-adjusted EPOCH plus rituximab/R-CHOP regimens and the prognosis analysis in patients with MYC, BCL2/BCL6 gene copy number gain lymphoma and double-hit lymphoma: results from a single institution retrospective clinical study.

PURPOSE: To compare the efficacy of rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) with traditional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimens in double-hit lymphoma (DHL) and gene copy number gain (CNG) lymphoma and to contrast the prognosis of these two disease types. METHODS: We retrospectively examined 127 cases of newly diagnosed diffuse large B-cell lymphoma (DLBCL), and used fluorescence in situ hybridization (FISH) to detect genetic abnormalities in MYC, BCL2, and BCL6. RESULTS: In the two schemes, the 2-year progression-free survival (PFS) was higher for R-DA-EPOCH group than for R-CHOP (79.8% vs 57.5%, P=0.002), this advantage was also reflected in 2-year overall survival (OS) (81.6% vs 58.5%, P=0.002). In double CNG patients, R-DA-EPOCH regimen was significantly better than R-CHOP (P=0.007 for PFS, P=0.010 for OS), and R-DA-EPOCH has the same advantage in DHL patients (P=0.001 for PFS, P=0.047 for OS). For the two disease types, the PFS for DHL was inferior to that for double CNG (52.9% vs 72.4%, P=0.008), while the OS was not significantly different (P=0.050). Subgroup analysis showed that the PFS for double CNG with MYC and BCL2 was superior to that for DHL with MYC and BCL2 (P=0.043), this trend is also seen in double CNG and DHL with MYC and BCL6 (P=0.036). However, the OS was not significantly different between the two subgroups. Multivariate analyses showed that in DLBCL patients with genetic abnormality detected by FISH, the treatment and disease types were independent prognostic factors. The adverse reaction rates were similar in R-DA-EPOCH and R-CHOP (P>0.05). CONCLUSION: Our retrospective study shows that DHL has a poorer prognosis than double CNG. Based on its improved lifetime and good tolerance, R-DA-EPOCH is a promising regimen for DHL or double CNG, which is expected to become the first-line treatment for high-risk DLBCL types based on more clinical research.