B-cell lymphoma is a heterogeneous group of disorders involving malignant proliferation of B lymphocytes, accounting for approximately 85%of non-Hodgkin lymphoma. Combined use of rituximab and chemotherapy remarkably improves the survival of pa-tients with B-cell lymphoma. Despite the increase in treatment response, some patients suffer relapsed or refractory lymphoma. Nu-merous novel treatment options have been developed in pre-clinical and clinical practice, including targeted therapies, auto-hemato-poietic stem cell transplantation, cellular immunotherapy, and radioimmunotherapy. This review describes recent advances in B-cell lymphoma treatment and discusses future perspectives.

Objective · To evaluate the efficacy and prognostic factors of ifosfamide-cisplatin-etoposide (ICE) chemotherapy as salvage regimen for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods · A retrospective analysis was performed on 84 relapsed/refractory DLBCL patients who were treated with ICE salvage regimen at Ruijin Hospital (Shanghai Jiao Tong University School of Medicine,China) from July 2004 to June 2016.Overall survival (OS) was analyzed by Kaplan-Meier method and multivariate Cox proportional hazards models.Results· Of the 84 patients who were treated with ICE regimen,37 (44.0％) patients had responses,including 26 (31.0％) achieving complete remission.The median number of cycles per patient was 3 (range 1-6 cycles).The 1-year and 2-year OS rates were 49.5％ and 30.0％,respectively.The median OS time was 12.2 months.On univariate analysis,patients with early progression/recurrence (P=0.041) and a high-intermediate/high risk according to the international prognostic index (IPI) (P=0.024) and NCCN-IPI (P=0.002) had poorer outcomes.While improved outcome was found in patients in complete remission after chemotherapy (P=0.000).The multivariate analysis revealed that the intermediate-high/high risk according to NCCN-IPI was an independent risk factor,and remission after chemotherapy was an independent prognostic factor for prolonging survival.Conclusion· The ICE regimen can be used as an effective salvage therapy for patients with relapsed/refractory DLBCL.

Objective: To validate the prognostic value of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy. Methods: A retrospective analysis in 162 PTCL patients who were initially diagnosed and treated in Rui Jin Hospital from January 2003 to May 2013 was conducted. Baseline characteristics were collected, and survival analysis was performed according to the IPI and NCCN-IPI model. Results: The estimated 5-year overall survival (OS) rate and progression free survival (PFS) rate were 33% and 20%, with median OS and PFS of 17.0 months and 9.2 months, respectively. Multivariate analysis indicated ECOG score (PFS: HR=2.418, 95%CI 1.535-3.809, P<0.001; OS: HR=2.347, 95%CI 1.435-3.839, P= 0.001) , specific extra-nodal sites (PFS: HR=1.800, 95%CI 1.216-2.665, P=0.003; OS: HR=1.608, 95% CI 1.054-2.454, P=0.027) and pathology type (PFS: HR=0.424, 95% CI 0.184-0.975, P=0.043; OS: HR=0.276, 95% CI 0.087-0.877, P=0.029) were independent prognostic factors of OS and PFS for the patients with PTCL. The survival rates of low risk patients based on NCCI-IPI were remarkably higher than the counterparts based on IPI (5-year OS 74% vs 54%, χ²=5.041, P=0.025, 5-year PFS 50% vs 38%, χ²= 5.295, P=0.021) . NCCN-IPI was outstanding to identify the subgroup of low risk patients with PTCL, who may benefit from conventional chemotherapy such as CHOP or CHOP-like regimen. Conclusion NCCN-IPI is more powerful for low risk PTCL patients and a strong supplement for IPI.

Objective To understand the real experience of kinesiophobia in patients after bone transport technique,providing references for taking targeted nursing interventions to alleviate kinesiophobia of patients.Methods Purposive sampling method was employed to select 15 patients who underwent bone transport technique in the Department of Traumatic Orthopedics in a tertiary A hospital in Guangdong Province from October to December 2023 as the research subjects.Phenomenological research method was utilized to conduct semi-structured interviews with the patients,and Colaizzi 7-step analysis method was applied for data analysis and theme extraction.Results A total of 3 themes and 11 sub-themes were extracted,including the existence of negative psychological experience(fear and concern regarding exercise,excessive alarm in response to pain,helplessness and sadness about the change of life,persistent reflection on past experiences,anxiety and confusion about the future),facing the dilemma of physiological symptoms(pain and discomfort,fatigue and disturbed sleep),taking diversified coping approaches(selecting avoidance strategies,conducting self-adjustment,seeking kinesiophobia related knowledge and exercise guidance,acquiring social support).Conclusion The experience of kinesiophobia in patients after bone transport technique is complex and varied.Medical and nursing staff should prioritize the psychological relief of patients after bone transport technique,pay attention to the assessment and management of kinesiophobia related symptom,provide professional guidance and assist with multi-dimensional support to help patients reduce the experience of kinesiophobia and promote recovery of patients.

OBJECTIVETo identify potential mutation in a Chinese family affected with Charcot-Marie-Tooth disease(CMT).

METHODSClinical data of the family was collected, and genomic DNA was extracted from peripheral blood samples of the family members. Seventy-two candidate genes of the proband were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The protein structure was predicted with PyMOL-1 software.

RESULTSA homozygous missense mutation c.1894G>A(p.E632K) was identified in the exon 11 of the SH3TC2 gene in the proband. Heterozygous c.1894G>A mutation was also detected in the proband's father, mother and daughter, but not in the healthy family members and 300 normal controls. Retrieval of the NCBI, HGMD and 1000 genome databases has verified the c.1894G>A to be as a novel mutation. Computer simulation has suggested that the mutation has altered the 3D structure of the SH3TC2 protein.

CONCLUSIONThe proband was diagnosed as CMT4C, for which the underlying gene was SH3TC2. This finding has expanded the spectrum of SH3TC2 mutation in association with CMT4C.

Adult ; Aged ; Base Sequence ; Charcot-Marie-Tooth Disease ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; Models, Molecular ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Proteins ; genetics ; Young Adult

Objective: To analyze the morbidity, clinical characteristics, therapeutic outcomes and prognosis of cardiac lymphoma. Methods: Individual patient data were obtained from pathology defined 10 cases of cardiac lymphoma from Jan 2000 to Jun 2016. The patient’s general information, clinical manifestation, pathological diagnosis, laboratory examination, cardiac involvement feature, cardiac complications, treatment, therapeutic effect and prognosis were analyzed. Results: Of 3 918 cases of lymphoma patients, 10 cases of cardiac involvement were identified, including primary cardiac lymphoma (PCL) in 1 case, secondary cardiac lymphoma (SCL) in 9 cases. Of the 10 patients in our analysis, the male-to-female ratio was 3∶2, with a median age of 55 (19-88) years old. The most presenting complaints were dyspnea in 7 cases, followed by chest pain in 5 cases, fatigue in 2 patients and edema in 2 cases. Pathological types included diffuse large B cell lymphoma (DLBCL) in 7 cases, T cell lymphoma (T-LBL) in 1 case, Hodgkin’s lymphoma (HL) in 1 case, and Burkitt lymphoma (BL) in 1 case. The sites of the heart affected by lymphoma in the PCL patient were right and left atriums with multiple nodules; and for SCL, the sites were mainly pericardium associated with a pericardial effusion in 5 cases, a pericardial mass in 2 cases. Congestive heart failure affects 7 patients and cardiac arrhythmias were identified in 4 cases mainly sinus tachycardia, atrial fibrillation and atrioventricular block. Except one untreated because of old age and poor performance, the rest of 9 patients were treated by either chemotherapy in 4 cases or chemotherapy combined radiotherapy (including the extracardiac sites) in 5 patients. With the median follow-up of 9 months, the one PCL patient achieved partial response (PR) , progress free survival (PFS) for 6 months and the overall survival (OS) for 21 months; in the cohort of 6 SCL patients cardiac involved at diagnosis, complete response (CR) was achieved in 1 case (16.7%) , PR in 3 cases, progressing disease (PD) in 2 cases, with the median PFS for 5 months and the median OS for 19 months; and for the other 3 SCL patients cardiac involved at progression, PR was achieved in 2 case and death in 1 case, with the median PFS for 4 months and the median OS unavailable because of censored data. Conclusion Cardiac lymphoma represents a rare subset of lymphoma, the most common type is DLBCL, and the main clinical manifestations are dyspnea and chest pain, always combined by arrhythmia and congestive heart failure. The main therapeutic regimen for cardiac lymphoma includes combined chemotherapy and the prognosis for patients with either PCL or SCL is usually poor.

Objective: To investigate the efficacy of RCDOP (Rituximab, cyclophosphamide, liposome doxorubicin, vincristine and prednisone) regimen in patients with de novo diffuse large B-cell lymphoma (DLBCL), especially in those patients with multiple extra-nodal involvement or Bulky diseases. Methods: A total of 87 newly diagnosed DLBCL patients who received RCDOP regimen from October 2012 to October 2017 were enrolled into this study. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test, and χ² tests were used for categorical data. Results: Among the 87 DLBCL patients treated with RCDOP regimen, 81 patients achieved complete remission (CR) or partial remission (PR), with ORR as 93.1%. Patients were further classified into groups, according to the risk factors, such as IPI scores, multiple extra-nodal involvement, bulky disease, age>60, tumor Ki-67>80%, elevated serum LDH level and advanced Ann Arbor stage. The progression-free survival (PFS, P=0.084) and overall survival (OS, P=0.515) had no statistical difference among the IPI low risk (0-1 score) group, intermediate risk (2-3 scores) group and high risk (4-5 scores) group. Similarly, no statistical difference were fou nd in PFS and OS of patients with extra-nodal involvements ≥2 (P=0.303 and P=0.624), with bulky disease (P=0.518 and P=0.466), with age>60 (P=0.600 and P=0.183), with elevated serum LDH level (P=0.054 and P=0.880), with advanced Ann Arbor stage (P=0.075 and P=0.286), and with tumor Ki-67 over 80% (P=0.190 and P=0.109), when compared with those of patients without these risk factors. Conclusion RCDOP can improve the therapeutic effect and prognosis of DLBCL patients with certain high risk factors, such as intermediate and high IPI risks, multiple extra-nodal involvements, bulky disease, age over 60, elevated LDH level, advanced Ann Arbor stage and tumor Ki-67 over 80%.

Objective: To evaluate the efficacy and prognostic factors of second-line regimens for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective analysis was performed in 98 patients with relapsed/refractory DLBCL who were treated with salvage regimens in Rui Jin Hospital from July 2004 to June 2016. Overall response rate (ORR) was evaluated after all treatment finished. Overall survival (OS) was analyzed by Kaplan-Meier method and multivariate by Cox proportional hazards models. Results: There were 60 males and 38 females with a median age of 55.5 (15-77) years. 48 (49.0%) patients responded to chemotherapy, and 32 (32.7%) patients achieved complete remission (CR). Factors affecting ORR were progression disease or refractory/relapse status less than 12 months after diagnosis (χ²=5.878, P=0.015) , IPI intermediate-high/high risk (χ²=5.930, P=0.015) and NCCN-IPI intermediate-high/high risk (χ²=4.961, P=0.026). No significance difference was observed in ORR between germinal-center B-cell type (GCB) and non-GCB (χ²=0.660, P=0.417). One-year and 2-year OS rates were 51.0% and 31.5%, with median OS at 13.17 months, respectively. Multivariate analysis indicated NCCN-IPI intermediate-high/high risk[HR=2.176 (95%CI 1.338-3.538) , P=0.002] and response to chemotherapy [HR=0.273 (95%CI 0.165-0.452) , P<0.001] were independent prognostic factors for survival. Conclusion NCCN-IPI is a valid predictor of outcome for patients with relapse/refractory DLBCL. Response to chemotherapy is an independent prognostic factor for better survival.

Objective·To analyze the clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma(DLBCL),including clinical characteristics,pathological characteristics,gene mutation profiles,and prognostic factors.Methods·One hundred and forty-nine patients with kidney-involved DLBCL,admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from July 2005 to November 2021,were retrospectively analyzed for their clinicopathological data,survival and prognostic factors,which included therapeutic methods,clinical outcomes,staging,etc.Gene mutation profiles were evaluated by targeted sequencing of 54 lymphoma-related genes.Prognostic factors were also analyzed based on the information mentioned above.Results·A total of 149 kidney-involved DLBCL cases were included,of which 89 patients(58.4%)were aged over sixty,121 patients(81.2%)were staged Ann Arbor Ⅲ?Ⅳ,27 patients(18.1%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or more,121 patients(81.2%)had elevated serum lactate dehydrogenase(LDH)level,111 patients(74.5%)had extranodal invasion in at least two organs and 131 patients(87.9%)scored over 2 points on the international prognosis index(IPI).The estimated 5-year overall survival(OS)rate and progression-free survival(PFS)rate of kidney-involved DLBCL patients were 52.2%and 50.4%respectively.Univariate analysis revealed that elevated serum LDH levels were an adverse prognostic factor for both OS(P=0.048)and PFS(P=0.033).In pathological characteristics,145 patients(97.3%)belonged to DLBCL,not otherwise specified(NOS)and 39 patients(26.3%)belonged to germinal center B-cell(GCB)according to Hans classification.Among 144 patients who could be evaluated for clinical outcomes,87 patients(60.4%)got complete response(CR).Targeted sequencing data from 75 kidney-involved DLBCL patients showed high mutation frequency in PIM1(n=23,31%),MYD88(n=22,29%),CD79B(n=21,28%)and KMT2D(n=18,24%),with CD79B mutation indentified as an adverse prognostic factor for OS in patients with kidney-involved DLBCL(P=0.034).Conclusion·Elevated serum LDH level is an adverse prognostic factor in patients with kidney-involved DLBCL.The prognosis of patients with CD79B mutations is poor.

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.