ABSTRACT
The results of long-term follow-up of patients (pts) with chronic myeloid leukemia (CML) do not lose their importance. Data from routine clinical practice are of particular interest. The use of 1 st (imatinib, IM) and 2nd generation TKI (2G TKI) led to a significant increase in survival, so the probability of death associated with CML could be significantly lower than the probability of death due to common causes of death other than CML. To analyze the overall survival (OS) and causes of mortality in CML pts treated in routine clinical practice in Russian Federation for a long period (>15 years) of time. The long-term follow-up data of the Russian part of the European LeukemiaNet (ELN) OSP EUTOS multicenter observational study were evaluated. The analyzed cohort consisted of 678 Ph/BCR-ABL-positive CML pts from 35 regions of Russia diagnosed in 2002-2006 with IM therapy initiation ≤6 months (mo) after diagnosis. Median (Me) age was 47(range 18-81) years (y), 47% males. Chronic phase, accelerated phase and blast crisis at diagnosis was in 631 (93%), 41(6%) and 6(1%) pts, respectively. The annual number of newly diagnosed pts was as follows: 2002 - 15 pts, 2003 - 38 pts, 2004 - 46 pts, 2005 - 206 pts, 2006 - 302 pts. The last update for 209 pts was done in Jun. 2021;last contact for 100 pts - in 2020, for 39pts - in 2019, for the other - before 2018. The date of the last contact/death could not be established for 14 pts. Statistical analysis included 661 pts, the OS was evaluated by Kaplan-Mayer method using the SAS 9.4 package. In total, 331 (50%) pts of the analyzed cohort were alive with the Me follow-up of 180 (range 2-232) mo or 15 y (range 2 mo-19,3 y). All pts started therapy with IM with 25% switched to 2G TKI in subsequent therapy lines. In total, 218 (66%) pts achieved MR4, 183 (55%) pts got MMR;46 (21%) of these pts with deep molecular response (DMR) were observed in hematology centers of Moscow. The 15-y OS in the total cohort was 63% (CI 59-70%)(fig.1). The OS by age groups was as follows: 18-40yy-75% (CI 73-82%), 40-60yy- 63% (CI 59-70%), 60-80yy- 37% (CI 30-45%). The most complete information was provided by Moscow centers (2 centers, 113 pts). The 15-y OS of pts receiving treatment in Moscow was significantly higher vs pts from other regions (32 centers, 548 pts): 75% vs 60%, p=0,0030 (fig.2). The mortality in the whole cohort of 661 pts was 35% (233 pts). Of these 233 pts, 112(48%) pts deaths were due to CML progression to AP or BP (including non-compliant cases);3pts (1,5%) died after allogenic stem cell transplantation (infection complications);the cause of death was unknown in 50 (21,5%) pts. The highest death rate from CML progression was at 4-9 y of follow-up. Deaths caused by concomitant diseases were in 68 (29%) pts: coronary artery disease/myocardial infarction/heart failure in 42 (62%) of 68 pts, acute ischemic stroke in 10 (15%) pts, second malignancies (Cr- cancer) in 10 (15%) pts (lung tumor, metastatic esophageal Cr, stomach Cr, brain tumor, sigmoid colon Cr, rectal colon Cr, melanoma, renal Cr, breast tumor, other hematological malignancies), accidents - 1 pt, liver cirrhosis - 2 pts, in 2 cases - respiratory virus infections complicated with pneumonia, 1 pt died due to Covid-19. Conclusions. The long-term follow-up of the multicenter study EUTOS OSP in 35 regions of Russian Federation allows not only to characterize the 15-y OS in CML pts but also provides the long-term outlook of the routine clinical practice. Probably, better OS of CML patients receiving treatment in Moscow (2 centers) may be related to organizational issues of interaction with the federal center, better monitoring and timely switching to 2G TKI therapy. The organization and support of multicenter studies may improve the situation with the treatment of diseases of the blood system. [Formula presented] Disclosures: Chelysheva: Novartis Pharma: Speakers Bureau;Pfizer: Speakers Bureau;Pharmstandart: Speakers Bureau;Bristol Myers Squibb: Speakers Bureau. Vinogradova: Pharmstandart: Speakers Bureau;Novartis Phar a: Speakers Bureau;Pfizer: Speakers Bureau;Bristol Myers Squibb: Speakers Bureau. Lomaia: Novartis: Honoraria;Pfizer: Honoraria;BMS: Honoraria;Pharmstandard: Honoraria. Voloshin: Abbvie: Consultancy, Speakers Bureau;Novartis: Consultancy, Speakers Bureau;Astra Zeneca: Consultancy, Speakers Bureau;Pfizer: Consultancy;Biacad: Consultancy, Speakers Bureau. Turkina: Pharmstandart: Speakers Bureau;Pfizer: Speakers Bureau;Bristol Myers Squibb: Speakers Bureau;Novartis Pharma: Speakers Bureau.
ABSTRACT
One of the formidable complications of SARS-COV-2 infection leading to death is coagulopathy. The mechanisms of the development of this pathology at the present stage have not been studied, and clinical blood tests indicate that against the background of normal blood clotting indices, only the Ddi-D-dimer protein exceeds the norm many times over. The aim of the study was to study and analyze biochemical parameters in patients of Primorsky Region (Russia) infected with SARS-COV-2 against the background of concomitant vascular pathology and the development of DIC syndrome. The authors came to the conclusion about the existence of two mechanisms of circulatory disorders in the vessels of the microvasculature, associated with the violation of the integrity of the vascular wall and destruction of erythrocytes. Further research is needed to study the mechanisms of SARS-CoV-2 aggression, leading to thrombotic complications.
ABSTRACT
The paper considers the possible mechanism of the pathogenesis of COVID-19 caused by SARS-COV-2, associated with damage to red blood cells, which the authors attribute to the main key target that triggers a cascade of reactions leading to multiple organ failure. The paper presents morphological evidence for the presence of pathological forms of erythrocytes characteristic of various anemias in the blood vessels and parenchyma of damaged lungs of patients with COVID-19. The death of red blood cells leads to cell ischemia and anemia. The defeat of brain neurons, blood vessels and hematotissue barriers in organ systems is a consequence of ischemia due to the impossibility of transferring hemoglobin by damaged erythrocytes and ends at the terminal stages of the development of the disease with their dysfunction. Adaptive erythropoiesis with an increase in erythropoietin secretion is especially dangerous for patients suffering from hypertension, and then it is impossible, since all organs involved in the synthesis of erythropoietin are damaged. In this case, the synthesis of hemoglobin is also disrupted due to a deficiency of iron and cyancobolamin, whereas toxic iron and hemosiderin are deposited in the tissues.