High-Grade B-Cell Lymphoma (HGBCL) with gene rearrangements in MYC and BCL2 and/or BCL6 is an aggressive malignancy usually presenting in advanced stages. Current recommendations suggest the use of regimens more intensive than R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), which are based on retrospective studies and single-arm prospective trials that included patients who are mostly in the advanced stage, and did not receive consolidation radiotherapy.

The optimal approach and treatment of HGBCL, whether limited-stage (LS) or advanced-stage, remains to be determined. Here we describe the promising outcomes of three patients with LS and low IPI HGBCL with the use of R-CHOP as induction chemotherapy regimen, which was followed by consolidation radiotherapy.

Three women, 54-, 60-, and 64-years of age diagnosed to have HGBCL with MYC, and BCL2 and/or BCL6 rearrangements, with Ann Arbor stages I-IIE were included in this case series. All three patients had complete metabolic response to 6 cycles of R-CHOP and was subsequently treated with consolidation involved site radiotherapy (ISRT; total dose 30-36 Gy). Chemotherapy and radiotherapy were tolerated very well. All patients remain to be in remission, with the longest being at 23 months.

Outcomes of patients with HGBCL generally remain to be poor, but this may not be the case for patients with limited-stage disease and favorable clinicopathologic risk profile. Nevertheless, the treatment of HGBCL is currently evolving and more studies are needed to determine the ideal approach and preferred chemotherapy regimen. Also, more studies are needed to elucidate the potential role of consolidation radiotherapy in patients with limited-stage HGBCL to improve survival outcomes. Findings of this case series suggest that patients with LS HGBCL may still derive benefit from R-CHOP followed by consolidation ISRT, but prospective trials are needed to confirm this.

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Classification of DLBCL is often based on the cell of origin (COO), distinguishing between germinal center B-cell (GCB) and non-GCB subtypes. Although not yet recognized as a distinct entity by the World Health Organization (WHO), double expressor lymphoma (DEL), characterized by the co-expression of c-MYC and BCL2, carries an unfavorable prognosis for a subgroup of DLBCL patients. Another entity is the so-called high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit/triple-hit lymphomas) diagnosed through fluorescent in-situ hybridization (FISH) analysis.

This study aimed to determine the clinicopathologic profile and survival outcomes of Filipino DLBCL patients at the Philippine General Hospital (2016-2021), comparing double-hit versus non-double-hit and doubleexpressor versus non-double-expressor lymphomas, and assessing concordance between FISH-measured double-hit and IHC-measured double-expressor statuses.

This is a single-arm, retrospective cohort study involving all surgical pathology cases signed out, with the aid of immunohistochemistry (IHC) studies, as NHL DLBCL, GCB, or non-GCB subtype, from 2016 to 2021. A second panel of IHC studies and FISH analysis using tissue microarray was subsequently done. Most cases exhibited a nonGCB subtype and were classified as DEL on second IHC panel. Five out of eleven DEL cases were reclassified as double hit lymphoma (DHL).

Clinically, most patients with these lymphomas present at age 60 years and below, exhibit B symptoms, with elevated serum lactate dehydrogenase (LDH) levels, at least stage III-IV disease at diagnosis, and possess a high International Prognostic Index (IPI) score, collectively indicating a poor prognosis.

Survival outcomes for patients with DLBCL ranges from three to 37 months. All cases of mortality were associated with DEL, contrasting with DHL cases which had variable outcomes. Due to limited sampling, statistical significance of the results cannot be determined. A comprehensive evaluation is essential to the diagnosis of DLBCL and DHL to include a complete immunohistochemistry panel and molecular testing, notably with FISH studies.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Classification of DLBCL is often based on the cell of origin (COO), distinguishing between germinal center B-cell (GCB) and non-GCB subtypes. Although not yet recognized as a distinct entity by the World Health Organization (WHO), double expressor lymphoma (DEL), characterized by the co-expression of c-MYC and BCL2, carries an unfavorable prognosis for a subgroup of DLBCL patients. Another entity is the so-called high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit/triple-hit lymphomas) diagnosed through fluorescent in-situ hybridization (FISH) analysis. Objective: This study aimed to determine the clinicopathologic profile and survival outcomes of Filipino DLBCL patients at the Philippine General Hospital (2016-2021), comparing double-hit versus non-double-hit and doubleexpressor versus non-double-expressor lymphomas, and assessing concordance between FISH-measured double-hit and IHC-measured double-expressor statuses. Methods: This is a single-arm, retrospective cohort study involving all surgical pathology cases signed out, with the aid of immunohistochemistry (IHC) studies, as NHL DLBCL, GCB, or non-GCB subtype, from 2016 to 2021. A second panel of IHC studies and FISH analysis using tissue microarray was subsequently done. Most cases exhibited a nonGCB subtype and were classified as DEL on second IHC panel. Five out of eleven DEL cases were reclassified as double hit lymphoma (DHL). Results: Clinically, most patients with these lymphomas present at age 60 years and below, exhibit B symptoms, with elevated serum lactate dehydrogenase (LDH) levels, at least stage III-IV disease at diagnosis, and possess a high International Prognostic Index (IPI) score, collectively indicating a poor prognosis. Conclusion Survival outcomes for patients with DLBCL ranges from three to 37 months. All cases of mortality were associated with DEL, contrasting with DHL cases which had variable outcomes. Due to limited sampling, statistical significance of the results cannot be determined. A comprehensive evaluation is essential to the diagnosis of DLBCL and DHL to include a complete immunohistochemistry panel and molecular testing, notably with FISH studies.
lymphoma ; lymphoma, large B-cell, diffuse ; cytogenetics ; immunohistochemistry

Humans ; Child ; Lymphoma, Large B-Cell, Diffuse/pathology*

Humans ; Rituximab/therapeutic use* ; Bendamustine Hydrochloride/therapeutic use* ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Lymphoma, B-Cell ; Protein Kinase Inhibitors/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome

Objective:b> To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods:b> Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results:b> Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion:b> There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.
Humans ; Myeloid Differentiation Factor 88 ; Disease-Free Survival ; Retrospective Studies ; China/epidemiology* ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Pancreas/pathology* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

BACKGROUND: To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution. METHODS: This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS). RESULTS: During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups. CONCLUSION Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.
Humans ; Rituximab/therapeutic use* ; Vincristine/therapeutic use* ; Retrospective Studies ; Prednisone/therapeutic use* ; Etoposide/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Cyclophosphamide/therapeutic use* ; Doxorubicin/therapeutic use*

OBJECTIVES: To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis. METHODS: The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24). CONCLUSIONS The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.
Child ; Adolescent ; Humans ; Rituximab/adverse effects* ; Lymphoma, B-Cell/drug therapy* ; Progression-Free Survival ; Remission Induction ; China ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance. METHODS: Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL. RESULTS: 227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ²= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×10⁹/L vs 8.23×10⁹/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037). CONCLUSION Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.
Child ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Cell Cycle Proteins/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; Ubiquitin-Protein Ligases/genetics* ; Prognosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Mutation ; Lymphocytes

OBJECTIVE: To discover the relationship between matrix remodeling associated 7 (MXRA7) and acute B lymphoblastic leukemia (B-ALL), and explore the effect of MXRA7 on the biological functions of B-ALL cell line REH. METHODS: The expression of MXRA7 in blood diseases was searched and analyzed through BloodSpot database. Real-time qPCR was used to detect the expression level of MXRA7 in B-ALL cell line 697 and REH cells. Lentivirus-mediated shRNA interference technology was utilized to knock down the expression of MXRA7 in REH cells. The effects of MXRA7 on the biological functions of REH cells were studied by in vitro experiments. Cell proliferation was detected by CCK-8 assay, cell cycle was detected by PI staining, cell apoptosis was detected by Annexin V and 7-AAD staining, and the expression of apoptosis pathway related proteins was detected by Western blot. RESULTS: Database analysis showed that MXRA7 was highly expressed in B-ALL patients, and real-time qPCR results showed that MXRA7 was also highly expressed in cell lines 697 and REH cells. Knockdown of MXRA7 in REH cells inhibited the cell proliferation and increased the percentage of G₀/G₁ phase cells. After treatment with cytarabine, the apoptotic ratio was increased in MXRA7-impaired REH cells, and the activation of caspase-3 and caspase-9 were also increased. CONCLUSION Knockdown of MXRA7 can reduce the malignancy of REH cells by inhibiting the cell proliferation and increasing the sensitivity of REH cells to cytarabine. These results indicate MXRA7 may be as a novel target for the treatment of B-ALL, and the potential usefulness of MXRA7 in B-ALL deserves further investigation.
Humans ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cytarabine ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*