Background: Patients (pts) with hematologic disease are at increased risk of severe SARS-CoV-2 infection. Recent observations reported poor outcomes of COVID-19 in pts with various cancer types and higher mortality rates compared with the general population. However, currently available data on COVID-19 in pts with hematologic disease are limited. Methods: CHRONOS19 registry is an observational prospective cohort study with the primary objective to evaluate the treatment outcomes in adult pts (age 18 or older) with hematologic disease and COVID-19. Secondary objectives are to describe severity and complications of COVID-19 and course of hematologic disease in SARS-CoV-2 infected pts, and to explore importance of various factors for disease severity and mortality. Pts with laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 were eligible for enrollment. Data were collected on a web platform and managed in a de-identified manner. Physicians from 8 hematology clinical centers and hospitals from all over Russia (Moscow, Ulan-Ude, Saransk, Vladimir, Nizhniy Novgorod, Kazan) participate in this study. Pts are followed for 30 days (ds) after COVID-19 diagnosis and up to 6 months (mos) for hematologic disease outcomes and overall survival assessment. The results of the first follow-up are presented in this interim analysis. Results: As of July 30, 2020, 184 pts were enrolled (females/males [n(%)]: 80(44%)/104 (56%); median [range] age: 55 [18-83] years. Disease type (malignant/non-malignant [n(%)]): 164(89%)/20(11%), including AML 36(20%), ALL 16(9%), MDS 5(2%), APL 5(2%), MM 38(21%), HL 4(2%), NHL 38(21%), MPN 9(5%), CLL 13(7%), others 20(11%). Concomitant diseases were in 95(52%) pts: cardiovascular 56(59%), pulmonary 6(6%), hepatic 6(6%) or renal 5(5%), diabetes 17(18%), obesity 4(4%), other 16(17%). 176 patients were evaluable for the primary outcome assessment with a median follow-up of 41(1-125) ds. Thirty-day all-cause mortality was 23% (41 pts died). Death due to COVID-19 complications occurred in 34 (83%) pts, 7(17%) pts died due to progression of hematologic disease. Fifty (28%) pts experienced COVID-19 complications, the most common were pneumonia in 125 (71%) pts, respiratory failure in 82(47%) pts, ARDS in 11(6%) pts, cytokine release syndrome in 15(9%) pts, multiple organ failure in 10(6%) pts, sepsis in 6(3%) pts, and pulmonary bleeding in 1(0,6%). Specific anti-COVID-19 treatment was given to 117 pts(67%) pts: most common first-line treatment was hydroxichloroquine+azithromycin in 84(72%) pts, azithromycin monotherapy in 27(23%) pts, other drugs in 6(5%) pts; second-line treatment comprised lopinavir+ritonavir in 38 pts, tocilizumab in 29 pts, umifenovir in 5 pts, baricitinib in 5 pts, canakinumab in 1pt, sarilumab in 1 pt. The rate of ICU admissions was 27%(47 pts), among them only 11(23%) pts survived, 36(20%) pts required mechanical ventilation, only 2(5.5%) pts survived. Eighty-eight(50%) pts received anticoagulants. With regard to the blood disease, treatment delays occurred in 101(57%) pts with a median 4 weeks, 6(3%) pts required change of treatment. At the first follow-up (30 ds) the rate of relapse / progression of hematologic disease was 16 of 151 evaluable pts (10.6%). Thirty-day overall survival was 75%. At the data cutoff, median overall survival was not reached. Antibody detection was performed in 70 pts: 53(76%) pts had IgG SARS-CoV-2 antibodies. Among factors possibly associated with poor survival were: stage of COVID-19 1(n=41) - 91,8%/ 2(n=75) - 90%/ 3(n=36) - 56,5%/ 4(n=22) - 13,6% (p<0,0001), concomitant diseases (n=93/81): 59,5% vs. 87% (p=0,0001), transfusion dependence (n=65/104): 58,1% vs. 81,8% (p=0,0007), prior steroid therapy (n=73/90): 64,6% vs. 82% (p=0,019), older age (<60 (n=108)/≥60 (n=68) years): 80% vs. 60% (p=0,048). Sex, disease type, myelotoxic agranulocytosis, and prior hematopoietic stem cell transplantation were not associated with worse outcomes. Data on the longer follow-up (90 and 180 ds) will be presented. Conclusions: Patients with hematologic disease and SARS-CoV-2 infection have high 30-day all-cause mortality predominantly due to COVID-19 complications. Stage of COVID-19, concomitant diseases, transfusion dependence, prior steroid therapy, and older age were associated with poor outcomes. Disclosures Shuvaev: Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. OffLabel Disclosure: hydroxichloroquine, azithromycin, lopinavir+ritonavir, tocilizumab, umifenovir, baricitinib, canakinumab, sarilumab for COVID-19 treatment

Telomere length can be measured by polymerase chain reaction (PCR), allowing to obtain the absolute length of telomeres (ALT) in base pair, and by flow cytometry, which can only estimate the relative telomere length. The aim of the study was to compare the results of the two methods and to develop an accurate and reliable way of converting the relative telomere length to absolute. The peripheral blood from 21 donors was analyzed. Measurement of leukocyte telomere length by flow cytometry was carried out using a commercial Telomere PNA Kit / FITC (Dako, Denmark) with two CytoFLEX flow cytometers (Beckman Coulter, China) and BD FACSCanto II (Becton Dickinson, USA), obtaining the molecular equivalent of fluorescence (MEF). To measure telomere length by real-time PCR, calibrators with a known number of telomeric repeats were prepared. Two quantitative PCRs were carried out: one for telomeric repeats, the other for determining the number of genome-equivalents of DNA, three times for each sample, which made it possible to calculate ALT. A strong direct relationship was found between the MEF obtained with BD FACSCanto II and CytoFLEX (r = 0.97). Analysis of PCR and flow cytometry results showed a significant correlation between ALT and MEF. We calculated the regression equations of ALT and MEF for CytoFLEX - y = 0.0043x (r = 0.84) and for BD FACSCanto II - y = 0.0051x (r = 0.82). Correlation analysis showed a high comparability of telomere lengths measured by two methods. The obtained regression equations allow converting the results of flow cytometry into absolute values, allowing the comparison of the results of different research groups and the use of this method in clinical trials.

Treatment programs for patients with acquired aplastic anemia include two main therapeutic options: allogeneic bone marrow transplantation and combined immunosuppressive therapy (IST). However, combined IST remains the method of choice for most adult AA patients. This study included 120 AA patients who received IST at the National Research Center for Hematology in 20072016. The analysis was applied to 120 patients. Median age was 25 (1765) years, M/F: 66/54, SAA/NSAA: 66%/34%. Effectiveness of IST was carried out in 120 patients with AA. This group did not include 8 SAA patients who died during the first 3 months from the start of treatment from severe infectious complications (early deaths 6.2%) and 2 AA patients who dropped out of surveillance. The observation time was 55 (6120) months. Paroxysmal nocturnal hemoglobinuria (PNH clone) was detected in 67% of AA patients. The median PNH clone size (granulocytes) was 2.5 (0.0199.5)%. The treatment was according to the classical protocol of combined IST: horse antithymocytic globulin and cyclosporin A. Most of patients (87%) responded to combined immunosuppressive therapy. To achieve a positive response, it was sufficient to conduct one course of ATG to 64% of patients, two courses of ATG 24% of patients and 2% of patients responded only after the third course of ATG. A positive response after the first course was obtained in 64% of patients included in the analysis. Most of the responding patients (93%) achieve a positive response after 36 months from the start of treatment. Therefore, the 3rd6th months after the first course of ATG in the absence of an answer to the first line of therapy can be considered the optimal time for the second course of ATG. This tactic allows to get an answer in another 58% of patients who did not respond to the first course of ATG. The probability of an overall 10-year survival rate was 90% (95% confidence interval 83.696.2).

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