Short- and long-term outcomes from the upfront high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation in diffuse large B-cell lymphoma

Introduction. Diffuse large B-cell lymphoma (DLBCL) is the most common (30-35%) type of B-cell lymphomas. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated by x6 CHOP-R only. High dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve an option to improve prognosis in these patients (pts).Aim. To improve prognosis in DLBCL IV stage, IPI ≥2 pts by upfront auto-HSCT.Materials and methods. Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 CHOP/EPOCH + R from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia were retrospectively analyzed. HSCT group includes pts with upfront HDCT followed by auto-HSCT (n = 35). The control group includes pts with non-invasive follow-up after induction only (n = 70). Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints were response rate, relapse rate and treatment toxicity.Results and discussion. The 3-yr OS (p = 0.01) and 3-yr PFS (p = 0.018) were significantly higher in HSCT group. The complete response rate was significantly increased after upfront auto-HSCT (p < 0.001). Early relapse served as an independent negative prognostic factor in OS (p < 0.001) and experienced statistically less in HDCT group (p = 0.027). Early (ER) and late relapse (LR) rate were higher in pts with DEL (ER - p < 0.001, LR - p < 0.001 in control group and ER - p < 0.001, LR -p = 0.013 in all pts). The overall relapse rate was higher if pts had >1 extranodal site with lung involvement (p < 0.004 in the control group and p = 0.021 in all pts). Prognostic models suggested DEL and presence of >1 extranodal site with lung involvement as an independent negative prognostic factors for increasing the relapse probability in two years after treatment.Conclusion. Upfront HSCT can serve as a clinical option to consolidate the first remission in IV stage DLBCL pts with DEL and/or >1 extranodal sites with lung involvement

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

Pharmacoeconomic analysis of heart rate slowing drugs in patients with ischemic heart disease

Aim. To compare the efficacy and cost/effectiveness ratio of the original and generic bisoprolol in achieving target heart rate (HR) in patients with ischemic heart disease.Material and methods. Patients with ischemic heart disease (n=60; 36 males and 24 females) aged from 35 to 75 years were included into the study. Patients were randomized into group A (received therapy based on the original bisoprolol) or into group B (received therapy based on of generic bisoprolol). Ivabradine was added, if the effect was insufficient. The duration of follow-up was 6 weeks. The HR dynamics was assessed during the study period. Cost/effectiveness ratio was calculated.Results. Significant HR slowing was found in both groups by the end of observation. In group A baseline HR was 70.0±5.6 beats/min and in 6 weeks - 58.1±3.8 beats/min, while in group B - 69.5±5.2 and 60.5±3.9 beats/min respectively. HR slowing was significantly higher in group A than that in group B. Direct costs in order to achieve a target HR in 1 patient for 6 weeks of therapy in group A were 663.75 rubles, while this in group B - 1093.58 rubles. Direct costs for HR deceleration by 1 beat in group A were 48.46 rubles vs 69.40 rubles in group B. The effect of therapy based on the original bisoprolol, is superior to that when generic bisoprolol used.Conclusion. HR-slowing effect of therapy based on the original bisoprolol was superior to that when generic bisoprolol was used. Pharmacoeconomic analysis revealed that HR deceleration was more economically profitable in treatment based on the original bisoprolol

TREATMENT EFFECTIVENESS AND SAFETY OF THE ORIGINAL AND GENERIC BISOPROLOL IN PATIENTS WITH ISCHEMIC HEART DISEASE

Aim. To compare the clinical efficacy and safety of original and generic bisoprolol compounds in patients with normal ejection fraction after acute coronary syndrome (ACS) with the outcome to stable angina.Material and methods. Totally, 60 ACS with the outcome to stable angina patients included, that had not reached target heart rate 55-60 bpm at rest, with mean age — 60,28±8,03 y.o. All patients were randomized to groups A and B. Patients from A group were taking original bisoprolol, B group were taking generic. Follow-up duration was 6 weeks. The dynamics of heart rate was assessed. For the factual drug intake there was calculation performed of the setting doses summation for pulse-decreasing drugs in each group using ATC/DDD-method.Results. In quantitative expression, in both groups there was significant reducing of HR by the end of observation. However, it was found that original bisoprolol decreases HR deeper, comparing to generic. The sum of setting doses for pulse-reducing drugs in A group in mean for 1 person was 33,5 mg by 6 weeks of therapy, in B group — 44,2 mg. To reduce HR by 10 bpm in A group, 28,15 mg needed of the sum of setting pulse-reducing drugs for 6 weeks, and in group B — 48,0 mg.Conclusion. Comparing two beta-blockers— original and generic bisoprolol, in ACS patients, it was shown, that original drug was significantly better than generic within pulse-reducing effect. Safety of the drugs did not differ

Prognostic impact of immunohistochemical and molecular genetic markers in Diffuse Large B-cell lymphoma

Aim. To evaluate impact of different clinical features on prognosis in Diffuse Large B-cell lymphoma (DLBCL) patients and to determine potential correlation between IHC markers (double-expression of c-myc, bcl-2 and p53) on unfavorable clinical characteristics in DLBCL patients.Methods. We analyzed 215 patients with DLBCL who received treatment from 2008 to 2016. We assess impact of different clinical features, such as B-symptoms, extranodal involvement, advanced stages and refractory course on PFS. In this study we also access potentially unfavorable impact of double expression of c-myc and bcl-2 and p 53 by immunohistochemical analysis.Results. In both uni- and multivariant analysis B-symptoms, advanced stages and primary-refractory course were identified as negative prognostic factors for PFS rates. We found tendency to correlation between double expression of c-myc and bcl-2 and high International prognostic index as well as expression of p53 and advanced stages (87,5% vs 56,4% respectively, р = 0,095). Сonclusion. Patients with DLBCL aggressive course of the disease (B-symptoms, advanced stages and primary-refractory disease) have lower rates of PFS. Double-expression of c-myc and bcl-2 and p53 can be potentially associated with aggressive course of the disease