[Detection of cytogenetic abnormalities in multiple myeloma by using optical genome mapping].

Multiple myeloma (MM) is a plasma cell neoplasm characterized by numerous chromosomal number and structural abnormalities, which are of great significance for risk stratification and response evaluation of MM patients. Optical genome mapping (OGM) is a novel technology that has the potential to resolve many of the issues and limitations associated with traditional cytogenetic methods. To date, the clinical utility of OGM has been validated in the fields of cancer, reproduction, and embryonic dysplasia, et al. In this study, we compared OGM to traditional techniques for the first time in five newly diagnosed MM patients, and evaluated the potential of OGM for detecting cytogenetic aberrations and its clinical application value in MM.

[Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement].

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma].

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

[Clinical features and prognostic factors of elderly patients with mantle cell lymphoma].

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

[Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19].

OBJECTIVE: To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19). METHODS: Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups. RESULTS: The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and NK cells, CD4+/CD8+ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8+ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8+ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs. 19 : 21 : 0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant (P=0.043). CONCLUSION: The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

[Analysis of clinical characteristics, treatment and survival of elderly patients with large diffuse B-cell lymphoma].

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.

[Correlation between multi-slice spiral CT determined epicardial adipose tissue volume and atrial fibrillation].

Objective: To determine the relationship between volume of epicardial adipose tissue (EAT) and atrial fibrillation (AF) . Methods: A total of 207 patients who hospitalized in the Department of Cardiology, Nantong University Affiliated Hospital from January 2016 to June 2018 were included in this study. They were divided into two groups, including AF group (n=125) and sinus rhythm group (n=82). The AF group included 80 paroxysmal AF (PAF) and 45 persistent AF (PeAF) patients. Total EAT and left atrial EAT (LA-EAT) volume were measured using 256 rows of multi-slice spiral CT in all patients. Echocardiographic derived left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) were analyzed. Hospholipase A2 and blood lipids were examined in all patients. The baseline data and EAT volume of all groups were compared. The multivariate logistic regression was used to analyze the risk factors related to the occurrence of AF. The correlation between total EAT volume and LA-EAT volume and LAD were analyzed by Pearson correlation. Result: The volume of total EAT in patients with sinus rhythm, AF, PAF and PeAF were (92.2±32.1), (136.0±46.0), (134.2±46.3) and (140.1±52.6)cm(3), respectively. The volume of LA-EAT in patients with sinus rhythm, AF, PeAF and PAF were (27.1±7.5), (39.2±19.2), (35.9± 17.0) and (45.1±21.5)cm(3), respectively. Total EAT and LA-EAT volume were significantly larger in PAF and PeAF groups than in sinus rhythm group (all P<0.01). The LA-EAT volume was larger in PeAF group than in PAF group (P<0.01), but total EAT volume was similar between two groups (P>0.05). Logistic regression analysis showed that total EAT volume (OR=1.202, 95%CI 1.083-1.334, P=0.001), LA-EAT volume (OR=1.051, 95%CI 1.003-1.101, P=0.037) and LAD (OR=1.019, 95%CI 1.005-1.032, P=0.006) were the independent related factors of AF. Pearson correlation analysis showed that the total EAT volume was positively correlated with LAD (r=0.466, P<0.01) and LA-EAT volume was positively correlated with LAD (r=0.290, P<0.01). Conclusion: The volume of total EAT and LA-EAT measured by 256-row multi-slice spiral CT is significantly correlated with the incidence of AF.

Integrative Palliative Cancer Care in Hong Kong: An Overview and an Example from the East.

Cancer is the most common cause of mortality worldwide. Although recent advances of multiple modality cancer management have significantly improved the cure and control rates, a significant proportion of patients are still refractory to the standard and available treatments. Early initiation of palliative care can reduce cancer suffering, improve health-related quality of life and possibly prolong survival. It also allows patients and their caretakers to perceive the trajectory of their cancer, so that better and advanced care planning can be contemplated and implemented. The traditional beliefs and perceptions of cancer also differ significantly between the East and the West, which may also affect the preferential approach to palliative care. This review provides an overview of palliative care services in Hong Kong, as compared with other parts of the world. In addition, we shall also explore how cancer perceptions affect the decision-making on palliative care.

[Efficacy of anti-CD19 CAR-T cell therapy in 10 refractory recurrent B cell malignancies].

Objective: To investigate the outcomes of anti-CD19 CAR-T cell for relapsed and refractory B cell malignancies. Method: Ten patients with relapsed and refractory B cell acute lymphocytic leukemia (B-ALL) and non-Hodgkin's lymphoma (NHL), diagnosed in the Department of Hematology of Peking University third Hospital from December 2015 to July 2017, were treated with anti-CD19 CAR-T cell therapy, and the efficacy and safety were analyzed. Results: Efficacy was assessed on the 28th day after cell infusion, including 66.7% (4/6) of complete remission (CR) for patients with ALL, 16.7% (1/6) of partial remission (PR), and 83.3% (5/6) of overall response rate (ORR). For NHL patients, CR was 33.3% (1/3) and most of the lesions disappeared in a patient with mantle cell lymphoma, but residual lesion presented persistent state. After infusion of anti-CD19 CAR-T cells, the main side effect was cytokine release syndrome (CRS) and fever. One patient presented with aphasia and the other one had multiple organ failure, which were improved after treatment. No patients died of CRS. Conclusion: anti-CD19 CAR-T cell for relapsed and refractory B cells hematological malignancies is safe, and the most problematic side effect is CRS, which can be controlled by therapy.

[Analysis of survival and treatment outcome of patients with primary diffuse large B cell lymphoma in reproductive system].

Objective: To analyze clinical feature and treatment outcome of patients with primary diffuse large B cell lymphoma(DLBCL) in reproductive system. Methods: A total of 26 patients with DLBCL in reproductive system were retrospectively analyzed, and the clinical features, laboratory data were included in Kaplan-Meier and prognostic analysis. Results: In our center, the incidence of primary diffuse large B cell lymphoma in reproductive system was 3.5% in all DLBCL patients, and the median age was 62.0 years. Male are more common with unilateral testicular involvement, and 38.5% patients belong to Ⅲ and Ⅳstage while 84.6% patients belong to non-germinal center B cell-like subgroup. The overall response rate(ORR) for the whole group was 88.5%. The complete response rate was 76.9%. The 3, 5-year progression free survival rate was 70.5% and 62.7% , and the 3, 5-year overall survival rate was 83.5% and 69.6%, respectively. The most common recurrent sites were contralateral testis and central nervous system. Rituximab can improve the survival of patients and combined with contralateral irradiation can furtherly improve progression free survival of patients(P=0.047). Clinical stage, B symptom, IPI, the level of LDH, and CRP, age>60 years, and initial treatment outcome were predictive of overall survival. Conclusion: Primary diffuse large B cell lymphoma in reproductive system is a rare type of extranodal DLBCL which occurs in older men with aggressive features. The most common sites of recurrence were contralateral testis and central nervous system. Surgery, rituximab , radiotherapy and prophylactic intrathecal injection can improve the survival of patients and may be the first-line treatment.

[Analysis of survival and treatment outcome of young patients with high-risk diffuse large B cell lymphoma].

Objective: To analyze clinical feature and treatment outcome of young patients with high-risk diffuse large B cell lymphoma. Methods: A total of 122 young patients with high-risk diffuse large B cell lymphoma who were treated in Third Hospital of Peking University during the period from January 2000 to April 2015 were retrospectively analyzed, and the clinical features, laboratory data were included in Kaplan-Meier and prognostic analysis. Results: In our center, the incidence of young high-risk DLBCL was 27.1% in all DLBCL patients, median age was 44.0 years, 99.2% patients belong to Ⅲ and Ⅳstage, 50% patients had more than two extranodal organs involvement, and the higher proliferation index(Ki-67≥80%) was present in 63.1% of patients, Immunohistochemistry showed that 36.7% patients in 30 cases were double-expressed DLBCL. The overall response rate(ORR) for the whole group was 79.4%, the complete response rate was 39.7% , the 3, 5-year progression free survival rate was 59.8% and 57.0%, the 3, 5-year overall survival rate was 63.5% and 57.8%, respectively. 44.3% patients were refractory-relapsed DLBCL. Rituximab can improve the survival of patients and 3-year overall survival rate was 75.2% vs 46.1%(P=0.001). High-dose chemotherapy was superior to CHOP regimen which 3-year overall survival rate was 84.6% vs 54.1%(P=0.006). Compared with chemotherapy group , auto-hematopoietic stem cell transplantation can improve prognosis of patients and 3-year overall survival rate was 93.4% vs 48.3%(P<0.001). The level of Ki-67, B symptom, ECOG score, the level of LDH, WBC and albumin, ESR level, anemia, rituximab therapy, initial regimens, ASCT, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated that albumin level(RR=5.462, P=0.019), initial treatment outcome(RR=34.863, P<0.001) and refractory-relapsed (RR=24.374, P<0.001)were independent prognostic risk factors. Conclusions: Young patients with high-risk DLBCL were highly aggressive in clinical and pathological features . Rituximab and high-dose regimens can improve the survival of patients.

Ablation of canine prostate using two-stage intraprostatic hot agarose solution and enzyme injection.

UNLABELLED: Enzyme ablation of the hyperplastic prostate may be an ideal method of management of BPH. However, the unsatisfactory ablation affects in vivo contrast with successful in vitro results limiting the enthusiasm for further research. In this study, we make efforts to solve the problems in the use of enzyme ablation of BPH in vivo and to measure satisfactory effect. MATERIAL AND METHODS: A total of 18 hybrid dogs between the ages of 7 and 11 y underwent this experiment. Eight dogs were divided into four groups according to the injection formula: enzyme solution, hot D-Hanks' plus enzyme solution, hot agarose plus enzyme solution, and hot agarose solution alone. After selecting the agarose plus enzyme solution group in the first month, the remainder 10 dogs were treated with this two-stage method. Intravenous or oral antibiotics were administered perioperatively. All operations were performed directly by way of laparotomy. The prostates were observed and harvested with surrounding tissue at 24 hrs, 7 days, 14 days, 1 month and 3-5 months after treatment. Gross and microscopic examinations were performed. RESULTS: Only agarose plus enzyme group shows obvious cavity formation with concomitant size reduction and softening of the prostate ablation effect in the four groups. At 24 h after injection, the prostates demonstrated cavity formation containing liquefied necrotic tissue. The liquefied tissue was absorbed in 7-14 days. At 1 month, the size of most prostates decreased with a corresponding decrease in the size of the cavities. The cavities nearly disappeared within 3-5 months, and the size of prostates decreased to between 1/2 and 1/4 of the pretreatment sizes. All prostates had intact urethral mucosa and capsule. No complications directly related to enzyme ablation were identified. In the control groups there were no significant cavities or decrease in prostate size. CONCLUSIONS: This two-stage thermal and enzyme ablative method can significantly ablate prostate tissue without identifiable complications, and would be possibly applied to treating human BPH in the future.