Association between serum albumin levels and survival in elderly patients with diffuse large B-cell lymphoma: a single-center retrospective study.

Background: In clinical hematology, diffuse large B-cell lymphoma (DLBCL) is notably heterogeneous and varies in prognosis. Serum albumin (SA) is considered a biomarker of prognostic value in a number of hematologic malignancies. However, current knowledge of the association between SA levels and survival is limited, especially in DLBCL patients aged ≥70 years. Thus, this study sought to assess the prognostic value of SA levels among this age group of patients. Methods: The data of DLBCL patients aged ≥70 years at the Shaanxi Provincial People's Hospital in China from 2010 to 2021 were retrospectively reviewed. The SA levels were measured using standard procedures. The Kaplan-Meier method was used to estimate survival time, and the Cox proportional hazards model for time-to-event data was used to identify potential risk factors. Results: The data of 96 participants were included in the study. The univariate analysis showed that B symptoms, Ann Arbor stage III or IV of the disease, high International Prognostic Index (IPI) scores, high NCCN-IPI scores, and low SA levels were prognostic factors for an undesirable overall survival (OS) rate. The multivariate analysis showed that a high SA level (hazard ratio: 0.43; 95% confidence interval: 0.2-0.88; P=0.022) was an independent prognostic factor of superior outcomes. Conclusions: An SA level ≥4.0 g/dL was identified as an independent biomarker of prognostic value for DLBCL patients aged ≥70 years.

A novel single-tube multiplex real-time PCR assay for genotyping of thiopurine intolerance-causing variant NUDT15 c.415C>T.

Thiopurines are commonly used in the treatment of acute lymphoblastic leukaemia and autoimmune conditions, can be limited by myelosuppression. The NUDT15 c.415C>T variant is strongly associated with thiopurine-induced myelosuppression, especially in Asians. The purpose of this study was to develop a fast and reliable genotyping method for NUDT15 c.415C>T and investigate the polymorphic distribution among different races in China. A single-tube multiplex real-time PCR assay for NUDT15 c.415C>T genotyping was established using allele-specific TaqMan probes. In 229 samples, the genotyping results obtained through the established method were completely concordant with those obtained by Sanger sequencing. The distributions of NUDT15 c.415C>T among 173 Han Chinese, 48 Miaos, 40 Kazakhs, and 40 Kirghiz were different, with allelic frequencies of 0.06, 0.02, 0.07, and 0, respectively. This method will provide a powerful tool for the implementation of the genotyping-based personalized prescription of thiopurines in clinical settings.

Low-dose tertiary prophylactic therapy reduces total number of bleeds and improves the ability to perform activities of daily living in adults with severe haemophilia A: a single-centre experience from Beijing.

Full-dose prophylaxis treatment for persons with haemophilia is not affordable in China due to its economic constraints, particularly in adults requiring higher clotting factor (CFC) doses. Low-dose tertiary prophylaxis for adults with severe haemophilia A (SHA) in Beijing became feasible and implemented when government insurance covering 85% CFC cost in Beijing began in December 2009. The aim of this study was to evaluate the benefits of low-dose tertiary prophylaxis in SHA adults. Analysis of data on 33 patients on low-dose tertiary prophylaxis (5-10 IU/kg, two to three times per week) at the Haemophilia Treatment Center, Peking Union Medical College Hospital between December 2009 and December 2013. The 33 patients (age 18-60 years, mean 33.4) were on prophylaxis for 20.8 ±â€Š9.9 months (compared with prior on-demand therapy for 20.0 ±â€Š11.7 months). Prophylaxis resulted in significant decrease in annual bleeding rate (ABR, 11.8 ±â€Š7.6 vs. 41.5 ±â€Š20.7, 71.1% reduction, P < 0.0001), and significant improvement in Functional Independence Score in Haemophilia (FISH) measurement reflecting improvement in self-care and mobility. Radiologic (Pettersson) joint score was neither improved nor deteriorated. Ten of the 33 patients originally wheel chair and bed-bound began to walk and function independently in their daily lives. Low-dose tertiary prophylaxis for adults with SHA in China is feasible and beneficial. Although the average ABR remained high, a significant improvement in self-care and mobility measured by FISH was observed. These promising clinical experiences form the basis for further formal studies with more defined therapeutic protocol and outcome measures for affordable prophylaxis regimens in haemophilia adults in China.

[Low-dose Tertiary Prophylactic Therapy for Severe Haemophilia A Adults in A Single Medical Center in Beijing Area].

OBJECTIVE: To investigate the benefit of low-dose tertiary prophylaxis in adults with severe haemophilia A(SHA). METHODS: Twenty-two SHA patients aged 18 to 60 years from the Haemophilia Centre of Peking Union Medical College Hospital, Beijing, China, were retrospectively observed from their one year on-demand treatment to one year tertiary prophylaxis using plasma derived factor 8 concentrates at 5-10 IU/kg 2-3x per week. All the patients had already developed arthropathy. Gilbert and the functional independence scores in hemophilia were used to assess the joint status and the ability in the activities of daily living of the patients. RESULTS: Comparing with on-demand therapy,the annual bleeding frequency during low-dose tertiary prophylaxis decreased significantly by 72.7%,from 39.9 ± 21.5 to 11.1 ± 7.2 (P<0.0001),the total Gilbert score decreased from 50.5±32.1 to 45.2±29.6(P<0.05),and the total functional independence score in hemophilia score increased from 18.6 ± 5.2 to 21.7 ± 4.1 (P<0.05). CONCLUSION Low-dose tertiary prophylaxis in adults with SHA is beneficial by reducing bleeding frequency, improving the health status of joints, and improving the activities of daily living, thus raising the quality of life.

BMI­1 is important in bufalin­induced apoptosis of K562 cells.

The purpose of this study was to analyze the effects of bufalin on the gene expression of K562 cells and on the expression of BMI­1 pathway constituents in K562 cell apoptosis. K562 cells were treated with bufalin, and the inhibition rate and apoptosis were detected by an MTT assay, flow cytometry and a microarray assay. BMI­1, p16INK4a and p14ARF were examined by quantitative polymerase chain reaction (qPCR). Bufalin induced significant changes in the gene expression of the K562 cells; 4296 genes were differentially expressed, 2185 were upregulated and 2111 were downregulated. The most upregulated genes were associated with transcription regulation, while the most downregulated genes were associated with the non-coding RNA metabolic processes and DNA repair. qPCR analysis demonstrated that BMI­1 was overexpressed in the K562 cells. Bufalin is able to downregulate BMI­1 expression levels in K562 cells prematurely and cause an increase in the expression levels of p16INK4a and p14ARF. Moreover, bufalin downregulated BCR/ABL expression levels in a time­dependent manner, and the expression of BCR/ABL was not associated with the upregulation or downregulation of BMI­1 expression. Bufalin may induce K562 cell apoptosis by downregulating BMI­1 expression levels and accordingly upregulating the expression levels of p16INK4a and p14ARF. Bufalin may also induce K562 cell apoptosis via downregulating BCR/ABL expression levels, and this pathway may be independent of the BMI­1 pathway.