Introduction.Patients with HL normally undergo a risk-adapted treatment based on PET scans. Regardless of HL treatment high efficiency, (80-90% remission), the search of new prognostic markers has been a continued process in recent years. This is related to the disease recurrence in 25-35% of patients in the first 5 years. The studies show that MDSC expands dramatically with tumor growth and causes a tumor immunosuppressed environment. The aim of this study is to investigate the number of MDSC in HL patients' peripheral blood and its correlation with clinical variables when the diagnosis and outcome first set. Methods .43 primary HL patients, (median age: 30, range: 19-78 years; male: 18, female: 25), were included in the study since April, 2018. 58.2% and 41.8% of patients have been diagnosed with early and advanced stages of HL, respectively, and received the ABVD or BEACOPP (14/esc) as a 1st-line treatment regimen. Peripheral blood mononuclear cells (PBMC) were isolated by ficoll density gradient centrifugation treatment, after 2-3 chemotherapy cycles (interim), and at the end of treatment (EOT). We assessed the E-MDSC count (CD33+CD11b+CD14-HLA-DR-) using the anti-human antibodies purchased from Beckman Coulter (Brea, CA, USA). We have also used a routine protocol of metabolic PET assessed according to Deauville criteria of response. Results.83.7% of patients achieved remission (CR/PR) during the follow-up period (median timeline: 18.9 months). We recorded a disease progression in 5 (11.6%) patients during and after the 1st line therapy, (time to relapse - 8 months). In addition, those patients had a high level of MDSC before treatment, which also remained high after interim and EOT-PET. Median of EFS has not been reached and we continue monitoring all patients. The HL patients who achieved remission had an increased E-MDSC percent (median 12.5%) compared to the age and gender control group, (median 2.03%), and the non-responders' one (median 20%). The number of NK-T (CD3+CD16+CD56+) cells increased by 15 % after EOT compared to pretreatment number, 9.2%, p=0.05. PBMC Evaluation at baseline.The E-MSDC count increases significantly with age: 3.1% vs 12.9% in HL patients under 25 years of age vs over 40, respectively p=0.014. Pretreatment MDSC levels were potentially associated with the disease stage: early stages (1A-2A and 2B) vs advanced stages (12% vs 3.9% vs 15%, respectively p=0.07). Our PET imaging tentatively correlated to the above levels. With that, patients with PET 5DS had a higher number of E-MDSC compared to a healthy control group, while the count is reduced in responders during and after treatment (p=0.06). Theoretically, this means that immunosuppression would be reduced and the antitumor immune response of the body would improve. PBMC Evaluation at interim response assessment.At this step, the age was also confirmed as an independent predicting factor in patients under 25 vs > 40, according to the MDSC level (6% vs 11.5%, respectively p=0.008). The level of E-MDSC was higher in patients who failed to achieve CR/PR (p=0.08). PBMC Evaluation at the EOT:90.6% (39/43) and 9.4% (4/43) of patients had a PET-negative and PET-positivestatus at the EOT, respectively (p < 0.05). We found a strong correlation between the EOT-PET and E-MDSC level. With this, patients with EOT-PET-ve had a lower E-MDSC expression vs EOT-PET+ve (12% vs 42% respectively, p=0.0007), which may potentially become a prognostic factor of response prediction. IPS is an important independent prognostic factor positively correlated to the MDSC count at EOT. In our study, patients in the high-risk group (3-4 IPS) had a significantly higher level of MDSC number than the low-risk group (1-2 IPS) and are more likely not to achieve a positive response to treatment (25% vs 18%, respectively p=0.02). Conclusion.The obtained results suggest that the higher level of MDSC number is associated with unfavorable prognosis of HL, reduce response rate. The challenge of strictly prognostic factor application leads to the research of biomarkers in the HL field. The discovery of new prognostic factors will improve an individualized approach to patient treatment and decrease the disease relapse risk. Disclosures No relevant conflicts of interest to declare.
Background:The burden of multiple myeloma (MM) is increasing over time in China. However, there is limited data to evaluate comprehensively the epidemiological characteristics of MM. Methods: Following the general analytical strategy used in GlobalBurden of Disease, Injuries, and Risk Factors Study 2019, we analysed the burden of MM including incidence, mortality, prevalence and disability-adjusted life years (DALYs) with 95% uncertainty interval (UI) in China. Trends in burden of MM from 1990 to 2019 were evaluated.Results: There were an estimated 347.45 thousands DALYs with an age-standardized DALYs rate of 17.05 (95% UI, 12.31-20.77) per 100,000 population in 2019. The estimated incidence case and deaths of MM were 18.79 thousands and 13.42 thousands, with agestandardized incidence and mortality rates of 0.93 (95%UI, 0.67-1.15) and 0.67 (95%UI, 0.50-0.82) per 100 000 population. The agespecific DALYs rates per 100,000 population increased more than 10 at age group 40-44 and reached a peak (93.82) at age group 70-74.Males had higher burden than females with about 1.5-2 folds sexual differences in age-specific DALYs rates in all age groups. From 1990 to 2019, the DALYs number of MM increased by 134% with changing from 148.48 thousands in 1990 to 347.45 thousands in 2019. Conclusion:The burden of MM increased doubly during the past 3 decades, which highlighted the need of establishment of effective disease prevention and control strategies in both national and provincial levels.
Background Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinical, pathological and molecular subtype of diffuse large B-cell lymphoma (DLBCL), accounts approximately for up to 7% of all its cases and 2-4% of all non-Hodgkin's lymphomas. The standard 1st line treatment of PMBCL does not currently exist. The treatment approaches are still differing all over the world. A few retrospective analysis and lack of prospective data comparing the efficiency of R-CHOP and DA-EPOCH-R regimen, does not allow to establish the best front line treatment options. Aims In current study we aimed to compare the treatment efficacy and toxicity of DA-EPOCH-R and R-CHOP regimens in patients with PMBCL. Patients and methods In the study were included 69 patients with newly diagnosed PMBCL from six Ukrainian centers from Aug 2011 to Dec 2015. Median age was 27 years (range 17-45), 50 females (72,5%) and 19 males (27,5%). Early stages (I-II) had 68,1 % patients, 78,3% of patients had greatest size of the tumor mass in mediastinum more than 10 cm. Patients were randomized in two groups: DA-EPOCH-R (36 patients) or R-CHOP (33 patients). Primary endpoint: 5-year PFS. Secondary endpoints: ORR, CR rate, PR rate, 5-year OS and toxicity rate. Primary and post treatment assessment of disease included PET-CT or CT of the whole body. The treatment efficacy in both groups was evaluated according to Cheson criteria 1999, 2007 and Deauville criteria. Toxicity rates were evaluated according to NCI-CTC V.3.0. All patients received 6 cycles of R-chemo ± mediastinal radiation therapy (30-36 Gy). Results ORR and CR were significantly higher in R-da-EPOCH group: 97.7% vs 85% and 81.8 vs 50%, respectively. 2,3% of patients in R-da-EPOCH group and 15% in R-CHOP didn't respond tothe therapy. There were any relapses after completion of treatment in DA-EPOCH-R group. In the R-CHOP group relapses were observed in 15% of patients (mostly early relapses). All relapses happened within 24 months after treatment. According to the analysis of long-term results, the 5-year PFS in the group of patients treated with DA-EPOCH-R was 90,9 % vs 64,1 % (p = 0.002) in the group of patients treated with R-CHOP. The 5-year OS in the DA-EPOCH-R group was 97.7% vs 73,8 % (p = 0.002), respectively. Neutropenia grade 3-4 was observed in 36,1% of cycles in R-da-EPOCH vs 20,6% in R-CHOP (p < 0.05) and FN in 15,7% vs 14,4% of cycles (p > 0.05). Anemia grade 3-4 was in 6,9% vs 8,7%, respectively(p > 0.05). Thrombocytopenia grade 3-4 was not observed. All cases of non-hematological toxicity were grade 1-2.ConclusionsThese results provide the confirmation by a multi-institutional study that DA-EPOCH-R regimen induses high durable remissions in PMBCL and more effective than traditional R-CHOP. Toxicity was tolerable in both groups, but the rate of neutropenia grade 3-4 was higher, but manageable in the group of R-da-EPOCH than in the group of R-CHOP. Disclosures No relevant conflicts of interest to declare.
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