Background: This study assessed the clinical characteristics of gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and the influence on long-term survival. Methods: A retrospective analysis was performed of 148 patients with PGI-DLBCL admitted to Peking University First Hospital from August 1994 to May 2018. The clinical characteristics of GIB, GIO, and GIP before and after chemotherapy were recorded. The associated overall survival and progression-free survival were analyzed. Results: Among 148 patients, 56.8% had gastrointestinal complications (GICs), including GIB, GIO, GIP, and multiple complications, and 22.6% of them occurred after chemotherapy, mostly during the first 4 cycles. The most common clinical manifestations of patients with GICs were abdominal pain or discomfort (79.8%), hematemesis or melena (22.6%), and abnormal bowel habits (17.9%). Patients with Eastern Cooperative Oncology Group (ECOG) score ≥ 2, tumor mass ≥ 10 cm, or intestinal involvement had significantly higher risk of severe GICs as initial manifestations. Among 130 patients who received chemotherapy, B symptoms, tumor mass ≥ 10 cm, and Lugano stage (IIE, IV) strongly correlated with GICs after chemotherapy (P < 0.05). Rituximab did not increase the risk of GICs. GICs which occurred before or after chemotherapy reduced the objective response rate at the end of chemotherapy. The prognosis of patients was significantly worsened by GIP, GIB, or multiple complications after chemotherapy (P < 0.05). GIB at presentation or GIO before or after chemotherapy had no prognostic value (both P > 0.05). Conclusion: GICs adversely affect the quality of life, prolong the length of hospitalization, and shorten the long-term survival of patients with PGI-DLBCL.

Background: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear. Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed. Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P< 0.001), ALP> 187.5IU/L (P=0.032) and ALB< 25g/L (P< 0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P=0.030) and Alb< 25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P< 0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002). Conclusion: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.

Objectives: Myelomatous pleural effusion is a rare presentation of extramedullary disease in multiple myeloma, which has been reported with dismal prognosis. We aimed to explore whether it has distinctive clinical characteristics and outcomes compared to other anatomic locations of extramedullary involvements. Methods: Multiple myeloma patients diagnosed at our institution from 2010 to 2020 were retrieved retrospectively. In total, 42 pairs of patients with and without extramedullary disease were enrolled, including 13 with myelomatous pleural effusion. The clinical and laboratory parameters were collected and compared between different groups. Prognostic effect of myelomatous pleural effusion was assessed in cox regression model and Kaplan–Meier curves. Results: Myelomatous pleural effusion patients presented a higher level of β2-microglobulin ( P = .041), greater prevalence of multisites extramedullary lesions (69.2% vs 38.0%, P = .036) and International Staging System stage III (76.9% vs 44.8%, P = .016). Median overall survival was 60.6 months in patients without extramedullary disease versus 35.0 months in patients with extramedullary disease ( P = .045). Notably, median overall survival was 13.0 months in myelomatous pleural effusion patients versus 37.0 months in other extramedullary disease patients with a significant difference ( P = .029). Furtherly, multivariate analysis recognized myelomatous pleural effusion as an independent prognostic indicator (Hazard ratio: 2.669, 95% CI [1.132-6.293], P = .025). Conclusion: Myelomatous pleural effusion patients presented heavier tumor burden and worse outcomes than other extramedullary diseases.

Background: 5-Hydroxymethylcytosine (5-hmC), a stable epigenetic marker, is closely related to tumor staging, recurrence and survival, but the prognostic value of 5-hmC in primary testicular diffuse large B-cell lymphoma (PT-DLBCL) remains unclear. This study aimed to investigate the 5-hmC expression in PT-DLBCL and evaluate its prognostic value.

Background: Progressive bone pain and fracture and abnormal positron emission tomography combined with a computed tomography are main reasons for the oncologists suspecting bone tumor. During the patient’s medical treatment, the oncologists’ unfamiliarity with adverse reactions to anti-HBV drugs were main reason for the long-term exposure to the drug and the adverse reaction (ADR) experienced by the patient. Case presentation: A 63-year-old Chinese man had a 27-month history of progressive generalized bone pain combined with spontaneous fractures. Positron emission tomography combined with a computed tomography, revealed an abnormal increase in ribose metabolism and low positron serum inorganic phosphorus concentration (0.7; 0.78–1.65 mmol/L). Serum creatinine level was 252 μmol/L (53–97) μmol/L, and glomerular filtration rate was 22.79 mL/min/1.73 m². The patient was referred to a multidisciplinary clinic to clarify the diagnosis of myeloma or bone tumor for further treatment in 2017. His medical history revealed that he had a 30-year history of chronic hepatitis B infection. He had received lamivudine at a daily dose of 100 mg for 19 years (1990 to 2009), which had been changed to adefovir (10 mg/day) owing to lamivudine resistance in 2009. Based on the changes in the patient’s laboratory markers and the results of emission computed tomography and other radiographic findings, adefovir-induced hypophosphatemic osteomalacia due to acquired renal Fanconi syndrome was suspected by the clinical pharmacist. Considerable clinical improvement was observed after adefovir discontinuation and the administration of entecavir (1.0 mg, every other day). Conclusion: Fanconi syndrome with osteomalacia can develop in patients with chronic hepatitis B infection being treated with adefovir at a conventional low dosage of 10 mg/day. This case highlights the importance of ADR as a differential diagnosis and the need of pharmacists with drug safety expertise expert in the patient management.

Background: 5-Hydroxymethylcytosine (5hmC), an important DNA epigenetic modification, plays a vital role in tumorigenesis, progression and prognosis in many cancers. Diffuse large B cell lymphoma (DLBCL) can involve almost any organ, but the prognosis of patients with DLBCL at different primary sites varies greatly. Previous studies have shown that 5hmC displays a tissue-specific atlas, but its role in DLBCLs at different primary sites remains unknown. Results: We found that primary gastric DLBCL (PG-DLBCL) and lymph node-involved DLBCL (LN-DLBCL) patients had a favorable prognosis, while primary central nervous system DLBCL (PCNS-DLBCL) patients faced the worst prognosis, followed by primary testicular DLBCL (PT-DLBCL) and primary intestinal DLBCL (PI-DLBCL) patients. Thus, we used hmC-CATCH, a bisulfite-free and cost-effective 5hmC detection technology, to first generate the 5hmC profiles from plasma cell-free DNA (cfDNA) of DLBCL patients at these five different primary sites. Specifically, we found robust cancer-associated features that could be used to distinguish healthy individuals from DLBCL patients and distinguish among different primary sites. Through functional enrichment analysis of the differentially 5hmC-enriched genes, almost all DLBCL patients were enriched in tumor-related pathways, and DLBCL patients at different primary sites had unique characteristics. Moreover, 5hmC-based biomarkers can also highly reflect clinical features. Conclusions: Collectively, we revealed the primary site differential 5hmC regions of DLBCL at different primary sites. This new strategy may help develop minimally invasive and effective methods to diagnose and determine the primary sites of DLBCL.