Linfoma no Hodgkin difuso de células B grande como linfoma primario de ovario. Presentación de caso / Diffuse large B-cell non-Hodgkin's lymphoma as primary ovarian lymphoma. Case presentation

Fundamento: Los linfomas primarios de ovario son poco frecuentes; el 1 % de estos se presenta en ovario y el 1.5 % de los tumores malignos de ovario son linfomas. Los tipos histológicos más frecuentes es el linfoma no Hodgkin difuso de células B grande y el BurKitt; el tratamiento consiste en cirugía combinada con quimioterapia. Objetivo: Reportar un caso de un linfoma no Hodgkin difuso de células B grande primario de ovario. Presentación de caso: Se presentó el caso de una paciente de 39 años de edad, con antecedentes patológicos personales de salud; la cual fue al cuerpo de guardia de ginecología por presentar dolor abdominal difuso que no se aliviaba con analgésicos. En la exploración física presentaba dolor a la palpación superficial y profunda en hipocondrio y fosa ilíaca derecha con masa tumoral palpable. Ecografía hacia proyección anexial derecha se observó una imagen de baja ecogenicidad y en la laparoscopia de urgencia se concluyó como una formación de aspecto tumoral que parecía corresponderse con ovario derecho. Se le realizó una histerectomía con doble anexectomía. El diagnóstico anatomopatológico fue un linfoma no Hodgkin primario de ovario. Conclusiones: La paciente del caso presentado tuvo una clínica oligosintomática y la confirmación de la enfermedad fue a partir de una muestra quirúrgica, lo que expresa que el diagnóstico del linfoma no Hodgkin de células B es difícil y aunque es poco frecuente siempre se debe tener en cuenta en el diagnóstico diferencial de las tumoraciones unilaterales de ovario.

Background: Primary ovarian lymphomas are uncommon, 1% of these malignancies occur in the ovary, and 1.5% of all ovarian malignancies are lymphomas. The most common histologic types are diffuse large B-cell non-Hodgkin's lymphoma and BurKitt's lymphoma; treatment consists of surgery combined with chemotherapy. Objective: To report a case of primary ovarian diffuse large B-cell non-Hodgkin lymphoma. Case presentation: A 39-year-old female case is presented, with a personal pathological history; she went to the gynecology emergency service because she presented diffuse abdominal pain that was not relieved by analgesics. Physical examination revealed superficial and deep pain on palpation in the hypochondrium and right illiac fossa with a palpable tumor mass. Right adnexal ultrasound showed an image of low echogenicity and at the emergency laparoscopy, it was diagnosed as a tumor-like formation that appeared to correspond to the right ovary. She underwent a hysterectomy with double adnexectomy. The anatomopathologic diagnosis was primary ovarian non-Hodgkin's lymphoma. Conclusions: The patient in the presented case had an oligosymptomatic clinical presentation. Confirmation of the disease was obtained from a surgical sample, which means that B-cell non-Hodgkin's lymphoma is difficult to diagnose and although it is uncommon, it should always be considered in the differential diagnosis of unilateral ovarian tumors.

Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Progress of microRNA in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Diffuse large B-cell lymphoma (DLBCL) as the most common type of non-Hodgkin lymphoma is not only invasive but also highly heterogeneous. After the first-line treatment, some patients still develop to refractory or relapse, and the survival time is significantly shortened. microRNA (miRNA) is a small molecule of endogenous non-coding RNA, which plays a role through post transcription. They can act as oncogenes to promote the development of cancer, or as tumor suppressor genes to prevent the occurrence of tumors. This article reviews the research progress of miRNA in DLBCL in recent years.

Analysis of incidence and influencing factors of interstitial pneumonia in diffuse large B-cell lymphoma after treatment of R-CHOP-like regimens / 白血病·淋巴瘤

Objective:To investigate the incidence of interstitial pneumonia (IP) and its risk factors in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) after treatment of R-CHOP regimen (rituximab combined with cyclophosphamide + doxorubicin + vincristine + prednisone) and R-CDOP regimen (rituximab combined with cyclophosphamide + vincristine + liposomal doxorubicin + prednisone).Methods:The clinical data of 54 newly-diagnosed DLBCL patients who were admitted to the Central Hospital Affiliated to Shandong First Medical University from January 2015 to August 2020 were retrospectively analyzed, of which 25 cases were treated with R-CDOP regimen, and 29 cases were treated with R-CHOP regimen. The incidence of IP was compared in patients stratified according to different clinically factors, and the risk factors of IP were analyzed by multivariate logistic regression.Results:The patients with R-CDOP regimen [compared with R-CHOP regimen: 32.0% (8/25) vs. 3.4% (1/29)], normal lactate dehydrogenase level before treatment [compared with high level: 29.0% (9/31) vs. 0 (0/23)], eosinophilic count>0.1×10 9/L [compared with ≤0.1×10 9/L: 28.0% (7/25) vs. 6.9% (2/29)] and Ki-67 positive index<80% [compared with ≥80%: 23.1% (9/39) vs. 0 (0/15)] had a higher incidence of IP (all P<0.05), there were no statistical differences in the incidence of IP among patients stratified with age, gender, smoking history, underlying disease, stage, international prognostic index score, Eastern Cooperative Oncology Group score, type, B symptoms, β 2-microglobulin, and lymphocyte count (all P>0.05). Multivariate logistic regression analysis showed that the application of R-CDOP regimen was the independent risk factor for the incidence of IP (compared with R-CHOP regimen: OR = 2.898, 95% CI 1.358-6.176, P = 0.008). Conclusions:The application of chemotherapy with R-CDOP regimen in DLBCL patients increases the incidence risk of IP, which needs to be closely monitored and prevented during treatment.

Clinical efficacy of chidamide combined with BEAC preconditioning regimen in high-risk or refractory diffuse large B-cell lymphoma receiving autologous hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of chidamide combined with BEAC (camustine+etoposide+ cytarabine+cyclophosphamide) preconditioning regimen in high-risk or refractory diffuse large B-cell lymphoma (DLBCL) receiving autologous stem cell transplantation.Methods:The clinical data of 10 high-risk or refractory DLBCL patients with autologous stem cell transplantation after receiving chidamide combined with BEAC preconditioning regimen who were admitted to Xuzhou Central Hospital from March 2022 to May 2023 were retrospectively analyzed. The related complications during preconditioning and hematopoietic reconstruction process, the time of hematopoietic stem cell reconstruction after transplantation, and the short-term efficacy were summarized.Results:Of the 10 patients, 6 were women and 4 were men; the median age was 58 years old (27-68 years old). Hematopoietic reconstruction was achieved in all 10 patients after transplantation. The median time of neutrophil engraftment was 11 d (range 7-12 d), and the median time of platelet engraftment was 12 d (range 9-16 d) after transplantation. Hematological adverse reactions were described as follows: 2 cases had grade 3 febrile neutropenia, 1 case had grade 4 febrile neutropenia, 3 cases had grade 2 anemia, and 1 case had grade 3 anemia. Non-hematological adverse reactions were described as follows: 1 case had grade 2 nausea with vomiting, and 1 case had diarrhea. Eight patients were followed-up for >3 months after transplantation, 6 patients achieved complete remission, 1 patient achieved partial remission, and 1 patient with TP53 deletion developed disease progression 1 month after transplantation.Conclusions:Autologous hematopoietic stem cell transplantation with chidamide combined with BEAC preconditioning regimen is effective for patients with high-risk or refractory DLBCL, and the adverse reactions are tolerable.

Progress of targeted drugs for treatment of diffuse large B-cell lymphoma / 白血病·淋巴瘤

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive lymphoma. The relapsed/refractory DLBCL patients have poor outcomes and DLBCL is still lack of effective treatment standard regimens. How to effectively treat relapsed/refractory DLBCL patients has become a research hotspot, and the current treatment methods include bispecific antibody therapy, chimeric antigen receptor T-cell (CAR-T) therapy, antibody-drug conjugates (ADC) therapy. This paper reviews the progress of targeted drugs/cell treatment for DLBCL at the 64th American Society of Hematology annual meeting.

Clinicopathological characteristics and prognosis of patients with diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological and molecular genetic characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinicopathological data of 152 DLBCL patients receiving consultation and routine physical examination in Peking University Third Hospital and Peking University School of Basic Medicine from January 2008 to December 2015 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of CD10, bcl-6, MUM1, GCET1, FOXP1. EB virus encoded small RNA (EBV-EBER) was detected by using in situ hybridization. The aberrations of bcl-2, bcl-6 and c-myc genes were detected by using fluorescence in situ hybridization (FISH) to screen double-hit lymphoma (DHL). Kaplan-Meier method was used to make survival analysis.Results:Among 152 cases of DLBCL, the ratio of male to female was 1.49:1, the median age of onset was 59 years (7-90 years), and 79 cases (52.0%) were primary lymph nodes. The median overall survival (OS) time of all cases was 16 months (1-101 months). The 1-year, 3-year and 5-year OS rates were 70.2%, 44.7%, 30.3%, respectively. The OS of R-CHOP treatment group was better than that of CHOP treatment group and untreated group ( P = 0.001). Among all 137 patients receiving double-hit histochemistry score (DHS), there were 56 cases with 0 score, 57 cases with 1 score, 24 cases with 2 scores; and the difference in the OS of different DHS score groups ( P = 0.311). FISH detection showed that among 29 cases achieving results of c-myc gene detection, there were 2 cases of splitting gene and 3 cases of gene amplification; among 26 cases achieving results of bcl-2 gene detection, 2 cases had bcl-2 gene amplification; among 26 cases achieving results of bcl-6 gene detection, 2 cases had bcl-6 gene amplification and 3 cases had splitting gene. It was found that myc and bcl-2 genes were amplified simultaneously in 1 case, accompanied with bcl-6 gene splitting, which was called triple-hit lymphoma. In DHS 0-score group, 1 case of double gene abnormality was found, and 1 case of single gene abnormality was found in group 1-score; in group 2-score, 5 cases were single gene abnormality and 1 case was three gene abnormality, so the gene abnormality was inconsistent with the protein expression. Conclusions:The incidence of DHL in DLBCL patients in China is low. The major gene abnormalities are c-myc or bcl-2, bcl-6 single gene abnormalities.

Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

Mutation of proviral integration site for Moloney murine leukemia virus 1 in diffuse large B-cell lymphoma and its clinical significance / 白血病·淋巴瘤

Objective:To investigate the mutation of proviral integration site for Moloney murine leukemia virus 1 (PIM1) in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:Paraffin-embedded tissues of 38 DLBCL patients surgically resected at Shiyan Taihe Hospital from January 2016 to March 2022 were collected. The mutation of PIM1 gene was detected by polymerase chain reaction (PCR)-Sanger sequencing. The DLBCL-related DUKE, DFCI and TCGA datasets in the cBioPortal database were screened to collect information on PIM1 gene mutation and expression and clinical prognosis. Patients were divided into PIM1 mutation-positive group and PIM1 mutation-negative group, and the differences in clinicopathological characteristics, tumor mutational burden (TMB), microsatellite instability (MSI) levels and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used for survival analysis, and univariate and multivariate survival analyses were performed using Cox proportional hazards model.Results:The PIM1 mutation rates of DLBCL patients in DUKE, DFCI, TCGA datasets and Shiyan Taihe Hosipital were 14.3% (96/673), 26.3% (26/99), 19.5%(8/41) and 28.9% (11/38), respectively, in which mutation site and mutation form were more commonly found in exon 4 and missense mutations. There were statistical differences in the PIM1 mutation rate among DLBCL patients with different age (DUKE dataset) and cell of origin (COO) classification (DFCI dataset) ( χ2 values were 8.22 and 4.40, both P<0.05). Compared with PIM1 mutation-negative group, the PIM1 mutation-positive group had a higher TMB in DUKE, DFCI and TCGA datasets (all P<0.05). In DUKE and DFCI datasets, the OS of PIM1 mutation-positive group was worse than that of PIM1 mutation-negative group (both P<0.05), and multivariate Cox regression analysis showed that PIM1 gene mutation-positive was an adverse prognostic factor of OS (DUKE dataset: HR = 1.661, 95% CI 1.151-2.396, P = 0.007; DFCI dataset: HR = 2.074, 95% CI 1.031-4.172, P =0.041). Conclusions:PIM1 gene mutation may be related to the poor prognosis of DLBCL patients.

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: 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: 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: 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.

The effect and safety of first-line autologous hematopoietic stem cell transplantation in elderly patients with moderate/high-risk diffuse large B-cell lymphoma / 中华老年医学杂志

Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.

Predictive value of multi-parameter model incorporating PET-based radiomics features for survival of older patients(≥60 years) with diffuse large B-cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the prognostic value of 18F-FDG PET-based radiomics features by machine learning in older patients(≥60 years) with diffuse large B-cell lymphoma (DLBCL). Methods:A total of 166 older patients (88 males, 78 females, age: 60-93 years) with DLBCL who underwent pre-therapy 18F-FDG PET/CT from March 2011 to November 2019 were enrolled in the retrospective study. There were 115 patients in training cohort and 51 patients in validation cohort. The lesions in PET images were manually drawn and the obtained radiomics features from patients in training cohort were selected by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (Xgboost), and then classified by support vector machine (SVM) to build radiomics signatures (RS) for predicting overall survival (OS). A multi-parameter model was constructed by using Cox proportional hazard model and assessed by concordance index (C-index). Results:A total of 1 421 PET radiomics features were extracted and 10 features were selected to build RS. The univariate Cox regression analysis showed that RS was a predictor of OS (hazard ratio ( HR)=5.685, 95% CI: 2.955-10.939; P<0.001). The multi-parameter model that incorporated RS, metabolic metrics, and clinical risk factors, exhibited significant prognostic superiority over the clinical model, PET-based model, and the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in terms of OS (training cohort: C-index: 0.752 vs 0.737 vs 0.739 vs 0.688; validation cohort: C-index: 0.845 vs 0.798 vs 0.844 vs 0.775). Conclusions:RS can be used as a survival predictor for older patients(≥60 years) with DLBCL. Furthermore, the multi-parameter model incorporating RS is able to successfully predict prognosis.

Predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for medium-term outcome in patients with primary gastrointestinal diffuse large B cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.

Relationship between 18F-FDG PET/CT Lugano lymphoma response evaluation criteria and prognosis at the end of chemotherapy for diffuse large B-cell lymphoma / 中华核医学与分子影像杂志

Objective:To investigate the relationship between 18F-FDG PET/CT Lugano lymphoma response evaluation criteria and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) at the end of chemotherapy. Methods:A total of 131 patients with DLBCL (63 males, 68 females, age (50.3±17.0) years) who underwent 18F-FDG PET/CT at the end of chemotherapy in the Fourth Hospital of Hebei Medical University from July 2013 to January 2021 were analyzed retrospectively. 18F-FDG PET/CT Lugano lymphoma response evaluation criteria was used to evaluate the response (complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD)). Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier survival analysis was used for univariate analysis of clinical parameters and imaging parameters, and Cox proportional hazards regression model was used for multivariate analysis to explore related factors affecting the prognosis of patients with DLBCL. Results:The median follow-up time was 35.47 months for 131 patients with DLBCL. The 5-year PFS rate was 57.3%(75/131), and the 5-year OS rate was 84.0%(110/131). There were 74 cases of CR, 37 cases of PR and 20 cases of PD. Univariate analysis showed that the Lugano lymphoma response evaluation criteria was the influencing factor of PFS and OS (PFS, χ2=72.25, P<0.001; OS, χ2=11.97, P=0.003). Deauville score (DS) of patients with DLBCL was also the influencing factor for PFS ( χ2=62.46, P<0.001) and OS ( χ2=19.95, P<0.001). Ann Arbor stage, Eastern Cooperative Oncology Group physical state (ECOG PS) score and international prognostic index (IPI) were the influencing factors for PFS ( χ2 values: 10.31-15.80, all P<0.05). Ann Arbor stage, ECOG PS score, number of extranodal organ involved, β 2 microglobulin, and IPI were the influencing factors for OS ( χ2 values: 4.97-30.57, all P<0.05). Cox multivariate analysis showed that Lugano lymphoma response evaluation criteria, Ann Arbor stage and ECOG PS score were independent prognostic factors for PFS (relative risk ( RR) and 95% CI: 8.841(4.764-16.405), 1.434(1.111-1.852), 2.125(1.205-3.746), P values: <0.001, 0.006, 0.009) and OS ( RR(95% CI): 3.276(1.304-8.235), 9.728(2.216-42.669), 2.506(1.040-6.039), P values: 0.012, 0.003, 0.041). Conclusion:18F-FDG PET/CT Lugano lymphoma response evaluation criteria can precisely evaluate the prognosis of patients with DLBCL at the end of chemotherapy.

Value of 18F-FDG PET/CT in the interim therapeutic and prognostic evaluation of primary gastrointestinal lymphoma / 中华核医学与分子影像杂志

Objective:To assess the value of 18F-FDG PET/CT imaging and relevant factors in the interim therapeutic and prognostic evaluation of primary gastrointestinal lymphoma (PGIL) patients. Methods:From January 2008 to January 2018, 41 patients with B-cell PGIL (24 males, 17 females; age: 26-84 years) confirmed by pathology in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively included. 18F-FDG PET/CT was performed before chemotherapy and radiotherapy and after 3-4 courses of chemotherapy. There were 17 cases of mucosa-associated lymphoid tissue (MALT) lymphoma and 24 cases of diffuse large B-cell lymphoma (DLBCL). Mann-Whitney U test was used to compare the differences of metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) before treatment between MALT lymphoma and DLBCL patients. ROC curve analysis was used to analyze the predictive abilities of different parameters for progression-free survival (PFS), and Cox regression analysis was used to analyze the influencing factors for PFS. Results:The median follow-up time of 41 patients was 25 (6-84) months, with the 3-year PFS rate of 55.9% and the overall survival (OS) rate of 80.2%. The baseline SUV max (23.2±11.9), MTV (260.7(66.2, 740.7) cm 3) and TLG (1 902.9(592.2, 8 418.1) g) in DLBCL were significantly higher than those in MALT lymphoma (7.9(6.2, 9.8), 45.9(28.4, 104.2) cm 3, 121.1(72.8, 295.6) g; z values: -4.02, -3.10, -3.92, all P<0.05). ΔSUV max in DLBCL patients (AUC=0.80, P=0.012), ΔSUV max% (AUC=0.89, P=0.007; AUC=0.80, P=0.012), ΔMTV%(AUC=0.91, P=0.005; AUC=0.77, P=0.026) and ΔTLG% (AUC=0.87, P=0.011; AUC=0.77, P=0.026) in MALT lymphoma and DLBCL patients before and after treatment were predictive factors of PFS. Multivariate analysis showed that ΔSUV max% was an independent factor for PFS of MALT lymphoma (hazard ratio ( HR)=17.192, 95% CI: 2.035-145.245, P=0.009), while ΔMTV% and ΔTLG% were factors for PFS of DLBCL (both HR=7.556, 95% CI: 1.968-29.016, P=0.003). Conclusions:There are significant differences in metabolic parameters between MALT lymphoma and DLBCL before treatment. Interim PET/CT is effective for the prediction of prognosis of MALT lymphoma and DLBCL.

Progress of the correlation of microRNA with diffuse large B-cell lymphoma and its treatment application / 白血病·淋巴瘤

MicroRNA (miRNA) plays an important role in the development of diffuse large B-cell lymphoma (DLBCL) by binding to the 3′ non-coding region of the target gene mRNA to regulate gene expression after transcription. The expression level of miRNA is closely related to the clinical staging, typing, prognosis assessment, and therapeutic effect of DLBCL. miRNA has a great potential as that of DLBCL-related biomarkers, and because of the close link between the two, miRNA-based therapies are expected to lead to new treatment options for DLBCL patients.

EB virus-positive discordant lymphoma: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical manifestations, laboratory tests, diagnosis and treatment of discordant lymphoma (DL).Methods:The clinical data of a patient with EB virus-positive DL admitted to Taizhou People's Hospital in November 2019 were retrospectively analyzed and the related literature was reviewed.Results:The patient underwent a cervical lymph node biopsy pathology examination at onset, and then results suggested angioimmunoblastic T-cell lymphoma (AITL). The patient subsequently developed gastrointestinal bleeding and underwent resection of small bowel lesions, and postoperative pathology suggested diffuse large B-cell lymphoma (DLBCL). The patient was finally diagnosed as DL. The R2-CHOP chemotherapy regimen was given to the patient, but the patient still had recurrent gastrointestinal bleeding and poor general condition. The patient refused chemotherapy and was changed to lenalidomide monotherapy. Finally, the patient died due to multiorgan failure, with an overall survival of 13 months.Conclusions:DL is rarely seen in lymphoma, whereas the combination of AITL and DLBCL is extremely rare. The clinicians need to improve the understanding of this disease to avoid misdiagnosis and missed diagnosis.

Sequential therapy of targeting CD19 and CD22 chimeric antigen receptor T-cell following autologous stem cell transplantation for renal diffuse large B-cell lymphoma with central nervous system recurrence: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of sequential therapy of targeting CD19 and CD22 chimeric antigen receptor T-cell (CAR-T) following autologous stem cell transplantation (ASCT) in treatment of renal diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence.Methods:The clinical data of 1 renal DLBCL patient with CNS recurrence admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology in May 2019 were retrospectively analyzed. The patient received sequential therapy of targeting CD19 and CD22 CAR-T following ASCT. The relative indicators of the primary disease remission at 1, 3, 6, 12, 18 and 24 months after therapy were analyzed, and relevant literature was reviewed.Results:The male patient aged 23 years had CNS recurrence after 8 courses of R-CHOP chemotherapy and then he received sequential therapy of targeting CD19 and CD22 CAR-T following ASCT. During the process of treatment, this patient developed grade 1 cytokine release syndrome and his condition was well controlled after active treatment. The white blood cell and platetes were successfully implanted. CNS symptoms along with immature cells in cerebrospinal fluid disappeared completely. Liquid biopsy was used to dynamically monitor the residue disease of the patient and the duration of remission period lasted 26 months. This patient developed tuberculosis one year after treatment and recovered from anti-tuberculosis agents.Conclusions:Sequential therapy of targeting CD19 and CD22 CAR-T following ASCT provides a novel therapeutic approach for renal DLBCL with CNS recurrence. Especially for patients who are neither sensitive to conventional chemotherapy nor CAR-T therapy alone, this regimen may improve remission rate and survival.

Expression of B7-H3 in diffuse large B-cell lymphoma and its prognostic significance / 白血病·淋巴瘤

Objective:To investigate the expression of B7-H3 in diffuse large B-cell lymphoma (DLBCL) and its prognostic significance.Methods:The paraffin-embedded tumor tissues of 103 patients with newly diagnosed DLBCL in Linyi Central Hospital from May 2013 to May 2019 were detected by using immunohistochemistry. The association of the expression of B7-H3 protein with the clinicopathological features, progression-free survival (PFS) and overall survival (OS) of DLBCL patients was analyzed. Cox proportional hazards model was used to analyze the factors affecting PFS and OS.Results:The positive rate of B7-H3 protein in patients with DLBCL was 68.0% (70/103). There were no statistically significant differences in the positive rate of B7-H3 protein among patients with different gender, age, clinical staging, international prognostic index (IPI) score, treatment effect, B symptoms, pathological type and other clinicopathological characteristics (all P > 0.05). The 5-year PFS and 5-year OS rates were 24% and 32% in all patients, the 5-year PFS rates were 47% and 14% in B7-H3 negative and B7-H3 positive patients, respectively ( P < 0.01); and 5-year OS rates were 50% and 24% in B7-H3 negative and B7-H3 positive patients, respectively ( P < 0.001). Multi-factor Cox regression analysis showed that B7-H3 positive was an adverse affecting factor of PFS ( HR = 2.685, 95% CI 1.503 - 4.789, P = 0.001) and OS ( HR = 2.262, 95% CI 1.248 - 4.098, P = 0.007). Conclusions:The moderate and high expression of B7-H3 may be related to the poor prognosis of DLBCL patients.

Effects of autologous hematopoietic stem cell transplantation as the first-line consolidation therapy for high-risk diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the long-term efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) as the first-line consolidation therapy for high-risk diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methods:From January 2010 to June 2017, 113 DLBCL patients admitted to Henan Cancer Hospital who had complete remission (CR) after rituximab combined with chemotherapy were enrolled. Among 113 patients, 40 cases received auto-HSCT as the first-line consolidation treatment after chemotherapy (transplantation group) and 73 cases received chemotherapy only (non-transplantation group). The clinical data of 113 patients were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and OS and PFS were compared between both groups.Results:The 2-, 3- and 5-year OS rates of transplantation group and non-transplantation group were 90.0% vs. 91.8%, 84.9% vs. 80.1%, 80.9% vs. 72.8%, respectively, and the difference in OS was statistically significant of both groups ( P = 0.457); the 2-, 3- and 5-year PFS rates were 85.0% vs. 85.0%, 82.2% vs. 61.8%, 82.2% vs. 60.0%, respectively, and the difference in PFS was statistically significant of both groups ( P = 0.046). None of the patients in the transplantation group experienced early transplantation-related death. Conclusions:In the era of rituximab treatment, the first-line auto-HSCT consolidation therapy could improve the PFS of high-risk DLBCL patients who are sensitive to chemotherapy, and it may improve the OS with a good safety.