Treatment Outcomes and Clinical Relevance in Patients with Double Expressor DLBCL.

BACKGROUND: Double-expressor lymphoma (DEL) was found to account for 20-30% of DLBCL. We conducted this study to analyze the survival, the clinical presentation, and the factors associated with treatment outcomes in DEL-DLBCL. METHODS: A retrospective study of 291 patients diagnosed with DLBCL during January 2015 - December 2018 was conducted. RESULTS: Of the 291 patients, the median age was 63 years, germinal center B cell-like DLBCL (GCB) and non-GCB subtypes were found in 32% and 68%, respectively. DEL was found in 46% of 264 patients with available immunohistochemistry staining for MYC protein. Patients with DEL was significantly more common in elderly patients (p= 0.017) and non-GCB subtype (p= 0.006). High serum lactate dehydrogenase (LDH) levels and high Ki-67 index were significantly found in DEL patients than non-DEL patients (p= 0.024 and p= 0.04, respectively). The 3y-OS rate was shorter in the DEL group than in the non-DEL group, 58.7% versus 78.9% (p=0.026), whereas no significant difference in 3y-DFS was identified between these groups (58.4% versus 67.7%, p= 0.343). Independent factors affecting OS and DFS in DEL patients were ECOG 3-4, high LDH levels, extranodal involvement> 1 site, high IPI, and stage III-IV in univariate analysis. CONCLUSIONS: High incidence of DEL was observed in this study, especially in patients aged 60 years or older and non-GCB subtype. Patients with DEL showed dismal DFS and OS.

Etiologies and Treatment Burden in Adult Patients with Pure Red Cell Aplasia: A Single-Center Experience and Review of Literature.

BACKGROUND: Pure red cell aplasia (PRCA) is less common blood disorder; the causes and the treatments of PRCA are varied. METHODS: We conducted a retrospective study during January 2010-December 2017, to explore the etiologies and to evaluate the response and treatment burden in adult patients with PRCA. RESULTS: Of 32 PRCA patients, median age was 57 years (18-90 years). Median hemoglobin level and reticulocyte count at the time of diagnosis were 5.6 g/dL (3.3-7.3 g/dL) and 0.3% (0.1-0.7%), respectively. Median time to hematologic recovery was 12 weeks (3-72 weeks), and median number of red blood cell transfusion (RBC) was 20 units (4-100 units). Causes of PRCA were erythropoiesis-stimulating agent (ESA) (47%), parvovirus B19 infection (19%), thymoma (13%), zidovudine (6%), primary autoimmune PRCA (6%), Kaposi's sarcoma (3%), systemic lupus erythematosus (3%), and ABO-mismatched stem cell transplantation (3%). Only 9 out of 24 treated patients achieved hematologic response within 8 weeks of treatment. Intravenous immunoglobulin therapy provided 100% response rate in patients with parvovirus B19-associated PRCA and primary autoimmune PRCA. Low response rate was found in patients receiving immunosuppressants and chemotherapy for the treatment of ESA and thymoma-associated PRCA, respectively. CONCLUSIONS: Treatment outcome of PRCA depended upon the causes and the types of treatment, and the burden of RBC transfusion was very high in patients with ESA and thymoma-associated PRCA.

Predictors for low disease activity and remission in rheumatoid arthritis patients treated with biological DMARDs.

BACKGROUND: Optimal outcome of treatment in rheumatoid arthritis (RA) is early clinical remission to delay joint damage. Therefore, severe RA patients with inadequate response to conventional disease modifying anti-rheumatic drugs (cDMARDs) need highpotency drug as biological DM4RDs (bDMARDs). In general, one-third of RA patient could not get into disease remission with cDMARDs, and half ofthem are still suffering from severe arthritis. However, high cost of this agent is the major barrier for patient engagement, and it is affordable to only 5-10% of patients. We need a good strategy to distribute bDMARDs to patients, especially in limited resource situation. OBJECTIVE: We explored the characteristics ofRA patients who were currently using biologic agents in Ramathibodi Hospital to determine the favorable treatment outcome. MATERIAL AND METHOD: The studied patients were RA patients classified according to ACR/EULAR 2010 criteria and using any biologic agents, between 2010 and2012. Demographic data and treatment outcome (low disease activity and remission) were retrievedfrom patient records. Univariate analysis and generalized estimating equation (GEE) were used to analyze predicting factors to control disease at one year. Kaplan-Meier and log rank test were used to analyze time to disease remission or low disease activity. RESULTS: Patients treated with bDMARDs in Ramathibodi Hospital demonstrated long disease duration (mean 130.7 months) and severe disease activity (mean DAS28 5.37). At 1-year after treatment, 19.4% and 12.9% ofpatients achieved low disease activity (low DAS) and disease remission, respectively. At 3-years after treatment, 88.9% and 45.2% of patients attained low DAS and remission. Patients who started bDMARDs after 2010 had significantly shorter time to control disease when compared to patients who started bDMARDs before 2010 (10 months vs. 34 months). Moreover, we observed that patient who started bDMARDs after 2010 using more cDMARDs (2.5 vs. 1.7, p = 0.02) and higher dose of methotrexate (10.7 vs. 6.5, p = 0.03). There were no association between disease control status and treatment (methotrexate, prednisolone, biologic agent) or disease duration. However the exposedstatus ofbiologic agent was associated with low DAS or remission at the first year of observation (p = 0.004 and 0.04, respectively). CONCLUSION: Chance to control rheumatoid arthritis in the level of remission or low disease activity is predicted by time of bDAMRDs exposure. This result is mainly influenced by dose ofmethotrexate and number of cDMARDs.

The effect of capsid mutations on HIV-1 uncoating.

Efficient uncoating requires not only an optimal cellular environment, but also some intrinsic properties of the viral capsid protein itself. Using an in vitro uncoating model, we demonstrated that substitution of each serine residue with alanine at the three major phosphorylation sites of HIV-1 capsid protein, i.e. Ser-109, Ser-149 and Ser-178, could significantly reduce uncoating activity of purified core particles. We also showed that the core stability of mutant viruses was lower than that of the wild-type virus so that the lack of efficient uncoating of each mutant could not be due to an increase in capsid physical stability. However, serine-to-aspartic acid mutation to mimic the negative charge of phosphor-serine could not restore either uncoating activity or infectivity, and treatment of purified core particles with a phosphatase did not alter the uncoating activity. Our data indicated that mutations at phosphoacceptor sites of capsid disturbed the uncoating mechanism, but the defect may not be directly caused by the lack of phosphate on the core particles undergoing uncoating.

Uncoating of HIV-1 requires cellular activation.

Uncoating is an essential step in viral replication cycle. Little is known about the mechanism and requirement of HIV uncoating. Using an in vitro uncoating model, we demonstrate here that the uncoating of HIV-1 was efficiently induced by lysate from activated CD4+ lymphocytes, while quiescent CD4+ lymphocyte lysate was unable to uncoat HIV-1 core. The uncoating activity was associated with an induction of in vitro reverse transcription of the viral genome. Using CD4+ lymphocytes that were arrested in cell cycle, we showed that the uncoating activity required transition of cells from G(0)/G(1a) into G(1b) stage. These results strongly suggested a requirement of cell cycle-dependent specific factors for HIV-1 uncoating. The putative HIV-1 uncoating factors could be fractionated from cell lysate by gel filtration chromatography.