Introduction. Currently, Ibrutinib is one of the most effective drugs for relapsed and refractory chronic lymphocytic leukemia treatment. In most patients with CLL, ibrutinib causes persistent remissions, but in some patients the disease progresses. Ibrutinib resistance in most cases is associated with the C481S mutation, which corresponds to the c.1441T>A and c.1442G>C substitutions in the BTK gene, however, other variants also exist.Aim — to evaluate variable allele fraction of the BTK gene mutations in patients with relapsed chronic lymphocytic leukemia using the in-house allele-specific real-time PCR test.Materials and methods. The study included material from 102 cases: 39 CLL patients with disease progression on ibrutinib therapy, 24 CLL patients with disease progression on the FCR/FCR-lite protocols, and 38 CLL treatment-naive patients. The control group included 118 patients with non-neoplastic hematological diseases.Results. Using in-house using AS-PCR, we detected the c.1442G>C mutation in 20 out of 39 CLL patients with progression on ibrutinib therapy. Mutation c.1442G>T was detected in 2 patients. In a single patient, two mutations were detected simultaneously: c.1441T>A and c.1442G>C. Another single patient had a combination of three mutations: c.1442G>C, c.1442G>T and c.1442G>A. In 15 patients with progression on ibrutinib therapy, mutations in the BTK gene were not detected. In treatment-naive CLL patients, in the group treated with FCR/FCR-lite regimens, and in the control group of patients with nonneoplastic diseases, mutations in the BTK gene were not detected.Conclusion. Variable allele fraction of exon 15 BTK gene mutations in the patients with CLL progression was successfully determined using in-house AS-PCR test: 50 % of patients had one mutation, 5 % had two mutations, and 2.5 % had three mutations in the BTK gene. Timely detection of these mutations before clinical recurrence may facilitate effective treatment strategy. Since clinical manifestations of ibrutinib resistance appear after an average of 1–2 years, we suggest monitoring BTK mutation load every 3 months in patients with CLL before relapse during treatment with ibrutinib.

Effective treatment and prevention of infections challenge management of patients with chronic lymphicytic leukemia (CLL). The COVID‐19 pandemic resulted in the reduction of outpatient hospital visits as a part of non‐pharmaceutical interventions that could affect the incidence of infectious complications. Study enrolled patients with CLL receiving ibrutinib or/and venetoclax who were observed at the Moscow City Centre of Hematology from 01 April 2017 to 31 March 2021. We found a reduction in the incidence of infectious episodes after the implementation of the lockdown in Moscow in 01 April 2020, when compared to data on the year prior to the lockdown ( p < 0.0001), as well as when compared to the predictive model ( p = 0.02), and based on individual infection profiles using cumulative sums ( p < 0.0001). Bacterial infections had 4.44‐fold decrease, bacterial in combination with undefined infections had 4.89‐fold decrease, viral infections had unsignificant changes. The decrease in the number of outpatient visits coincides with the time of the lockdown could be a likely factor, explaining a decline in the incidence of infection. Patients were clustered according incidence and severity of infectious episodes for subgroup mortality assessment. No differences in overall survival due to COVID‐19 were observed. Typical respiratory infections, bacterial and undefined, the transmission of which may be affected by patient‐to‐patient contact in the settings of out‐patient health care visits were decreased, possibly due to SARS‐CoV‐2 restrictive measures. A positive correlation between outpatient visits and the incidence of bronchial and upper respiratory tract infection points at the role of hospital‐acquired infection and attests to the necessity of reorganizing care for all patients with CLL.

BACKGROUND:Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and nonmalignant hematologic diseases and COVID-19.PATIENTS AND METHODS:Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-days all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic.RESULTS:Thirty-days all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-months overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients.CONCLUSION:Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed.

New Bruton’s tyrosine kinase (BTK) inhibitors caused drastic modifications in the therapy of chronic lymphocytic leukemia (CLL). Ibrutinib, the first in its class BTK inhibitor, showed high efficacy in many clinical studies. However, the treatment with BTK inhibitors as monotherapy must not be discontinued. Ibrutinib monotherapy inevitably leads to BTK inhibitor resistance and severe adverse events, which often results in treatment failure. Inhibitor BCL-2 venetoclax combined with BTK inhibitor can increase the therapy efficacy due to the synergetic effect of these agents on different CLL cell populations. Combined therapy potentially providing fixed-duration treatment can yield deeper responses. The present review focuses on ibrutinib and venetoclax combination, summarizes the latest data from clinical studies, and deals with feasibility of combined therapy in terms of its efficacy and safety profile.

Introduction. Optimal therapy for elderly patients with chronic lymphocytic leukemia (CLL) is the subject of intensive research. Aim – to study the safety of obinutuzumab, as well as the selection of the optimal scheme of its use in patients with CLL, complicated by diabetes mellitus, renal insuffi ciency, cardiac comorbidity. Materials and methods. The study included primary patients with CLL having indications requiring therapy. The inclusion criteria were: Cumulative Illness Rating Scale, CIRS) (CIRS) > 6 and or glomerular fi ltration rate (GFR) < 70 mL/min, the lower limit of GFR was not restricted. The study focused on patients with diabetes mellitus, renal failure and signifi cant cardiac pathology. Patients with Richter’s syndrome, CNS involvement, HBs-antigen, and 17p deletion were not included. In the fi rst cycle obinutuzumab was administered at a dose of 100 or 25 mg on the fi rst day and 900 or 975 mg on the second day, then at a dose of 1000 mg on days 8 and 15. For all subsequent cycles, obinutuzumab was given at a dose of 1000 mg on day 1. The dosage of chlorambucil was 10 mg/m2 from days 1 to 7. Treatment cycles in totals of 6 were repeated every 28 days. Results. The study included 90 patients. Median age was 73.5 years, range – 60–89 years, there were 49 men (54 %) and 41 women (46 %). Twenty-four patients (27 %) had stage C, IGHV unmutated status was detected in 76 % of patients. The median creatinine clearance was 48.6 mL/min (25–110). The median CIRS score was 3 (range – 1–14). Thirty-one patients (34 %) had signifi cant cardiovascular comorbidity (previous myocardial infarction, coronary artery stenting or bypass, HF ≥ II NYHA, peripheral artery disease) as well as hemodynamically signifi cant valvular disease. Fifteen patients (17 %) had diabetes mellitus and 71 patients (79 %) had creatinine clearance < 70 ml/min. Infusion reactions to obinutuzumab grade ≥ II were reported in 29 patients (32 %). Hospitalization on the day of administration or the next day after the fi rst administration was required in 5 cases (5.5 %). Twenty-seven (30 %) patients could not complete 6 cycles. The largest number of patients (14 people, 15.5 %) stopped treatment after 1 course. The causes were the development of persistent cytopenia (n = 4), grade IV reaction to obinutuzumab (n = 3), patient’s refusal (n = 2), infectious complications (n = 2), severe tumor lysis syndrome (n = 1), acute pancreatitis (n = 1) and toxicodermia (n = 1). The leading cause of premature discontinuation on subsequent cycles was persistent neutropenia. Progression during treatment occurred in 3 patients only. Overall survival was signifi cantly predicted by CIRS (maximum discriminatory value of 3, p = 0.013) as well as GFR < 50 mL/min (p = 0.03). No other associations were identifi ed. At least 1 episode of grade III–IV neutropenia occurred in 41 % of patients. Grade IV neutropenia was associated with creatinine clearance < 60 mL/min (p = 0.05), baseline neutrophil level < 2 × 109/L (p = 0.0001), baseline monocyte level < 0.3 × 109/L (p = 0.007) and age > 70 years (p = 0.01). The effectiveness of treatment was evaluated in patients who completed at least 3 cycles of therapy. Complete remission was achieved in 26 patients (35 %), partial remission – in 41 (54 %), stabilization – in 4 (5 %), progression was noted in 3 (4 %). Sixteen patients (18 %) were not available to respond to the assessment. Minimal residual disease < 0.01 % in the bone marrow after completion of treatment was found in 17 patients (19 %), within 0.01–0.9 % – in 25 (28 %) patients. The median follow-up from the date of therapy initiation was 39.7 months (range – 0.6–72 months). The median relapse-free survival was not reached, and 2- and 3-year survival rates were 81 and 62 %, respectively. Poor relapse-free survival signifi cantly correlated with unmutated IGHV genes (HR = 2.4, 95 % CI: 1.12–5.0, p = 0.02) and partial response as opposed to complete response (HR = 3.35; 95 % CI: 1.45–7.7, p = 0.03). Conclusion. The results of our study have practical implications as obinutuzumab is actively integrated into modern treatment regimens. Infusion reactions pose a high risk of complications in elderly patients. The dose of obinutuzumab on day 1 of administration in elderly patients, should not exceed 25 mg. The G-Clb regimen may not be optimal in patients over 75 years of age due to the unpredictable risk of complications. In patients at high risk of neutropenia, it may be appropriate to consider primary prophylaxis. ClbG is an effective regimen that resulted in high rate of MRD-negative responses and prolonged relapse-free survival.

We describe a retrospective cohort, 156 patients with chronic lymphocytic leukemia (CLL) diagnosed with COVID-19, analyze factors associated with a severe disease course and the effects of various treatment regimens. Anti-SARS-CoV-2 IgG and IgM levels are significantly lower. Patients with CLL are more likely to have a severe course of COVID-19, with IL-6 levels acting as a consistent biomarker of disease severity. Ten patients had recurrent episodes, fatality rate of 20%. Overall survival did not differ between patients receiving ibrutinib monotherapy and anti-CD20 antibodies +/- chemotherapy. It seems that the immunodeficiency inherent to CLL influences outcomes to a larger degree than does the treatment. Glucocorticoids are not associated with significant OS improvement whereas anti-cytokine compounds usage seemed to be beneficial in patients with mild pulmonary involvement. Our data attest to the necessity of reorganizing health care for patients with CLL. Early administration of effective antiviral compounds and tailored vaccination protocols are warranted.

Background: In the largest study of Baliakas et al. (2019) the presence of at least 5 abnormalities, was associated with dismal clinical outcome, independently of the somatic hypermutation status and TP53 status. The presence of 3 or 4 aberrations is defined as clinically relevant in the absence of TP53. Studies by Kittai (2021) and Al-Sawaf (2020) showed the impact of karyotypic complexity on survival in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib or venetoclax. The complex karyotype (CK) is a topic that is being intensively researched, both in the aspect of increasing karyotypic complexity stratification and clonal evolution. Optimal therapy for patients with CLL has not yet been developed. The combination therapy of ibrutinib and venetoclax was superior to chlorambucil and obinutuzumab in terms of undetectable minimal residual disease (MRD) responses according to data from the GLOW trial (Tunir, 2021). The importance of achieving a complete response with undetectable MRD as the goal of therapy in CLL was proposed (Montserrat, 2005). Aims: The aim of our study is to evaluate the effectiveness of therapy with ibrutinib and venetoclax in combination for the patients with CLL and CK. Methods: This ambilinear observational study included patients with CLL with high genetic complexity (high-CK), defined as >=5 aberrations or CK (>=3 aberrations) in combination with a 17p deletion (CK+del17p). The first retrospective cohort included patients treated with ibrutinib monotherapy (Imono) to progression or intolerable toxicity since May 2015. The second prospective cohort included patients receiving ibrutinib in combination with venetoclax (IVen) since July 2019. Venetoclax therapy was started at the 3rd month of ibrutinib (from the escalation phase). Combination therapy was continued until a complete response, defined as three consecutive PET-CT-negative and MRD-negative results 3 months apart. If this criterion was not achieved at 24th month of therapy, venetoclax was discontinued and ibrutinib continued indefinitely. Results: Seventy-nine patients are included in the study. Twenty-nine patients in the first cohort and 50 patients in the second cohort. The characteristic is presented in Table. At the current follow-up periods, there were no significant differences in PFS and OS regarding a follow-up period <= 24 months (with the exception of death from COVID-19, since patients were not observed at parallel time intervals). In the group of patients treated with Imono, the majority of patients achieved partial remission or partial remission with lymphocytosis by 12 months. In 21 patients from Iven group, with a median follow-up of 7.4 months, a complete remission was achieved (72.4%); of these, 8 had unmeasurable MRD. Four patients did not complete the escalation period. There was a significant difference in the median MRD response achieved between 3 (log10>10) and 12 (log10<0,1) months in IVen group (p=0,03). In 2 patient from the IVen group progression of the disease was noted. Image:Summary/Conclusion: Combination therapy with ibrutinib and venetoclax is an effective oral regimen for high-risk patients with complex karyotype disorders. PFS in both groups is currently not significantly different, which is obviously due to the short follow-up period. Patients receiving the IVen regimen achieve a significantly better response, which paves the way for allogeneic transplantation in these patients.

The clinical course of the new coronavirus disease 2019 (COVID-19) has shown that patients with chronic lymphocytic leukemia (CLL) are characterized by a high mortality rate, poor response to standard treatment, and low virus-specific antibody response after recovery and/or vaccination. To date, there are no data on the safety and efficacy of the combined vector vaccine Sputnik V in patients with CLL. Here, we analyzed and compared the magnitudes of the antibody and T cell responses after vaccination with the Sputnik V vaccine among healthy donors and individuals with CLL with different statuses of preexposure to coronavirus. We found that vaccination of the COVID-19–recovered individuals resulted in the boosting of pre-existing immune responses in both healthy donors and CLL patients. However, the COVID-19–naïve CLL patients demonstrated a considerably lower antibody response than the healthy donors, although they developed a robust T cell response. Regardless of the previous infection, the individuals over 70 years old demonstrated a decreased response to vaccination, as did those receiving anti-CD20 therapy. In summary, we showed that Sputnik V, like other vaccines, did not induce a robust antibody response in individuals with CLL; however, it provided for the development of a significant anti-COVID-19 T cell response.

Since SARS-CoV-2 infection heavily affects vulnerable populations including those with immune suppression, it is of special value to study clinical course, treatment outcomes, and immunity in patients (pts) with hematological (hem) malignancies. CHRONOS19 is an ongoing observational study in adult pts (≥18 years) with hem diseases (malignant or non-malignant) and COVID-19 in Russia. This web-based registry collected de-identified data from 15 centers all over the country at 30, 90, and 180 days after lab-confirmed or suspected (based on CT and/or clinical symptoms) COVID-19 diagnosis. The primary endpoint was 30-day all-cause mortality. As of data cut-off on April 14, 2021, 626 pts were enrolled in the study; 562 were eligible for primary endpoint assessment, n (%): M/F 271 (48%) / 291 (52%), median age 56 [18-90] years, malignant disease in 516 (92%) pts, among them induction phase / relapse or refractory / remission / NA in 180 (35%) / 120 (23%) / 187 (36%) / 29 (6%) pts. Thirty-day all-cause mortality in pts with hem malignancies was 19%; 83% of deaths were due to COVID-19 complications. No increase of hem disease relapse rate after COVID-19 was observed at Day 90 or Day 180, although 180-day data was still not mature at the time of analysis. IgG to SARS-CoV-2 was detected in 84% of pts with hem malignancies (167/199). The highest rate of detected antibody immunity was found in pts with chronic myeloproliferative neoplasms (100%; 13/13), HL (100%; 12/12), and multiple myeloma (97%; 34/35), the lowest – in pts with CLL (62%; 8/13) and NHL (60%; 6/10 and 56%; 10/18 for low-grade and high-grade lymphoma, respectively). igG detection rate in CD20+ lymphoma (60%) was significantly lower than in HL or T-cell lymphoma (p=0.004). Pts with ECOG 0-2 throughout the disease had a high rate of antibody immunity (90%; 104/116) vs. those with ECOG 3-4 at the time of COVID-19 diagnosis (77.5%; 31/40) or with worsening of ECOG to 3-4 during the disease (78%; 36/46). Five cases of SARS-CoV-2 re-infection were described. Pts with hem malignancies and COVID-19 have higher mortality than the general population. Low post-disease antibody immunity to SARS-CoV-2 and cases of re-infection may justify vaccination of these pts and warrant further research.

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]

Relevance. Infections are the most common complication of chronic lymphocytic leukemia (CLL). According to registry studies, infections are the cause of death in 10–20% of patients. The emergence of new therapies for CLL has led to a decrease in mortality due to CLL progression, while mortality from infections has remained constant in recent decades.The aim of this literature review is to analyze the effectiveness of vaccine prophylaxis in patients with CLL as well as predictors of vaccine inefficiency according to published data, to explore current guidelines.Conclusions. The mechanisms of immune dysfunction in CLL are complex and associated with both the disease itself and the therapy. Numerous studies have shown that patients with CLL have an inadequate response to most vaccines given routinely in the general population. Vaccination in CLL patients remains a poorly developed topic. Additional clinical trials are needed to improve the effectiveness of vaccination in patients with CLL.

Background: Research on the impact of COVID-19 on different patient populations has been of great value for the optimization of patient care since the start of the SARS-CoV-2 pandemic. Earlier, we reported the interim analysis of the immediate outcomes in patients (pts) with hematologic (hem) disease and COVID-19. Long-term results of the CHRONOS19 registry are now available.

Chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically with the recently developed drugs targeting the B-cell receptor (BCR) signalling pathway. Acalabrutinib, a second generation Bruton tyrosine kinase inhibitor, was approved in 2020 in Russia for the treatment of patients with CLL. Acalabrutinib was developed as a more selective Bruton tyrosine kinase inhibitor then ibrutinib. This drug is aimed at reducing the adverse events that limit the use of ibrutinib, such as atrial fibrillation and bleeding. Phase I/II multicenter studies have demonstrated the efficacy and safety of acalabrutinib monotherapy in untreated CLL patients and in patients with relapsed/refractory CLL and ibrutinib intolerance. Phase III trials, ASCEND and ELEVATE-TN, compared acalabrutinib monotherapy and a combination of acalabrutinib and obinutuzumab versus standard therapies and demonstrated improved efficacy and tolerability of acalabrutinib. A phase III trial comparing acalabrutinib and ibrutinib monotherapy (ELEVATE-RR) is ongoing. The results of this study along with real-life clinical data could determine the place of acalabrutinib in CLL treatment.

Background: Patients (pts) with acute leukemia (AL) are at high risk of COVID-19 severe and lethal course. Intensive chemotherapy and immunosuppression in these patients are the possible causes of high mortality. Emerging data on risk factors and outcomes in this vulnerable patient population is aimed to support strategies of their medical care. Aims: To evaluate treatment outcomes and risk factors in pts with AL and COVID-19 in a real-world setting. Methods: CHRONOS19 [NCT04422470] is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hematologic disease (both malignant and non-malignant) and lab-confirmed or suspected (based on clinical and/or CT findings) COVID-19. We performed a subgroup analysis of pts with AL and COVID-19. Primary objective was to evaluate treatment outcomes and identify risk factors associated with higher mortality in this group of pts. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web-based platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 132 of them with AL were eligible for primary endpoint assessment n(%): AML - 86(65%), ALL - 37(28%), APL - 9(7%);M/F 55(42%)/77(58%), median age 45 [18-79] years, induction phase/R/R/ treatment in remission 49(37%)/27(21%)/ 54(42%), agranulocytosis in 55(42%) pts, 68(53%) pts were transfusion dependent, comorbidities - in 58(45%) pts. Complications developed in 98(74%) pts: pneumonia (71%), sepsis (9%), CRS (8%), ARDS (6%). One-third of pts had severe COVID-19, 30% were admitted to ICU, 26% required mechanical ventilation. We performed comparative analysis of characteristics between a group of pts with AL and other hematologic diseases (lymphomas, chronic leukemia, multiple myeloma, and other malignant and non-malignant diseases): pts with AL had significantly more frequent agranulocytosis (42% vs 20%, p 60 years HR, 3.340 (1.08-10.9) were the most significant risk factors of death. Overall, AL were associated with a higher risk of death, HR, 2.40 (1.28-4.51), compared to less aggressive diseases (CML, CLL, MM, lymphomas, non-malignant), HR, 0.54 (0.37-0.80). COVID-19 affected treatment of AL in 65% of pts, 58% experienced treatment delay for a median of 4 [1-10] weeks. In 11 of 103 (10,7%) pts with AL early relapse/refractory disease was detected, but the association of relapses with affected treatment is unknown. COVID-19 re-infection was described in 2 patients. Summary/Conclusion: Thirty-day all-cause mortality was significantly higher in SARS-CoV-2-infected pts with AL than in those with other hematologic diseases. Longer-term follow-up (180 days) for AL outcomes and OS will be presented.

Background: Patients (pts) with lymphoproliferative diseases (LPD) are at high risk of COVID-19 severe and lethal course.Objective: To evaluate treatment outcomes and risk factors in pts with LPD and COVID-19 in a real-world setting.Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (18 y) pts with hematologic disease and COVID-19.Data from 15 centers were collected on a web-based platform and managed in a de-identifi ed manner.We performed a subgroup analysis of pts with LPD and COVID-19.Primary endpoint was 30-day all-cause mortality.Long-term follow-up was at 90 and 180 days.Results: As of data cutoff on April 14, 2021, 626 pts were included, 170 of them with LPD were eligible for primary endpoint assessment n(%): CLL -64 (38%), Hodgkin lymphoma -18 (10%), B-cell lymphomas aggressive/indolent -49(29%) / 19(11%); M/F 96 (56%) / 74(44%), median age 56 [19-90] years, induction phase/ R/R/remission 62(36%) / 68(40%) / 40(24%); comorbidities in 86 (51%) pts.Complications occurred in 126 (74%) pts; one-third had severe COVID-19, 25% were admitted to ICU, and 20% required mechanical ventilation.Comparative analysis of basic characteristics between pts with LPD and all other hematologic diseases did not reveal any signifi cant clinical differences.All-cause mortality at 30 days was 14% in pts with LPD vs 15% in pts with other hematologic diseases (p=0.87);86% of deaths were due to COVID-19 complications.Eight additional deaths due to COVID-19 at 90 days and 5 deaths due to LPD progression at 180 days occurred.In multivariate analysis, ICU + mechanical ventilation (HR,), and age >60 years (HR, were the most signifi cant risk factors of death.COVID-19 affected treatment of LPD in 55% of pts, and 52% experienced treatment delay for a median of 4[1-10] weeks.Early relapsed/refractory disease occurred in 5 of 170 (2.9%) pts; the association of relapses with impaired treatment is unknown.COVID-19 re-infection occurred in 1 patient.Data on antibodies after SARS-CoV-2 infection are available for 65 patients with LPD: anti-SARS-CoV-2 IgG was detected in 44 (66%) pts and only in 60% of pts with CD20-positive LPD vs 100% of pts with T-cell and Hodgkin lymphomas (p=0.004).Conclusions: Thirtyday all-cause mortality in SARS-CoV-2-infected pts with LPD was comparable with other hematological diseases and higher than in the general population.Lower frequency of anti-SARS-CoV-2 IgG in CD20-positive patients is probably due to anti-CD20 therapy.

В последнее время в связи с разработкой лекарств, мишенью которых являются звенья сигнального пути В-клеточного рецептора (B-cell receptor – BCR), существенно изменились подходы к терапии хронического лимфолейкоза (ХЛЛ). В 2020 г. в Российской Федерации для лечения пациентов с ХЛЛ одобрен акалабрутиниб, ингибитор тирозинкиназы Брутона II поколения. Акалабрутиниб разработан как более селективный ингибитор тирозинкиназы Брутона по сравнению с ибрутинибом. Данный препарат нацелен на уменьшение ограничивающих применение ибрутиниба нежелательных явлений, таких как фибрилляция предсердий и кровотечения. Многоцентровые исследования I/II фазы продемонстрировали эффективность и безопасность монотерапии акалабрутинибом у пациентов с ХЛЛ, ранее не получавших лечение, и у пациентов с рефрактерным/рецидивирующим ХЛЛ, а также непереносимостью ибрутиниба. Исследования III фазы, ASCEND и ELEVATE-TN, сравнивали монотерапию акалабрутинибом или комбинацию акалабрутиниба и обинутузумаба со стандартными методами лечения и продемонстрировали бoльшую эффективность и лучшую переносимость акалабрутиниба. Ко времени написания обзора продолжалось исследование III фазы – сравнение акалабрутиниба и монотерапии ибрутинибом (ELEVATE-RR). Результаты этого исследования и данные реальной клинической практики помогут прояснить оптимальное использование акалабрутиниба в лечении ХЛЛ.

Intoduction . Multiple myeloma (MM) and chronic myelogenous leukaemia (CML) are two haematological malignancies developing through tumour transformation of lymphoid and myeloid progenitor cells, respectively, not sharing a common ancestry. Coexistence of the two diseases is extremely rare. Aim . Clinical description of a patient diagnosed with CML in a few months after start of MM therapy. Main findings . We report a clinical case of MM and CML in a 62 years-old female patient. MM was diagnosed newly and followed by 5 VD chemotherapy cycles. Treatment discontinued due to severe polyneuropathy. The patient was transferred to thalidomide maintenance therapy. CML was diagnosed 12 months after initiation of thalidomide therapy: BCR-ABL (p190), BCR-ABL (p210). Since imatinib produced short-term effect, dasatinib therapy was started. Following 16 months after the onset of dasatinib therapy, MM relapse and CML progression were diagnosed.

Here we provide a review of the literature and a description of our own clinical case. The patient was a 32-year-old woman who had been infected with HIV for 6 years without antiretroviral therapy. The test results showed CD4 87 cells/l, viral load 3750 copies/ml. Normochromic normocytic anemia and reticulocytopenia developed soon. In the myelogram, all erythroblasts were 0.5%. The viral load of parvovirus B19 DNA according to PCR was more than 9 million IU/ml. Pure red cell aplasia associated with parvovirus B19 was diagnosed. We started antiretroviral therapy with efavirenz, lamevudine and tenofovir. In addition to blood transfusions, we administered intravenous donor immunoglobulin with a dose increase from 5000 mg to 20 000 mg per day. After discontinuing of intravenous immunoglobulins, the laboratory test results were stable over the next 5 months: hemoglobin was more than 115 g/L, reticulocytes more than 3%, in the myelogram all erythroblasts were 21%. However, the elimination of parvovirus B19 wasnt achieved. The maximum decrease in viral load for parvovirus B19 was down to 720 IU/ml. A typical feature of the case was the lack of pure red cell aplasia of the bone marrow with the existing viral load of parvovirus B19. HIV infection progressed: 44 cells/l, viral load not determined. The case ended lethally.

Eight patients were observed with a rare combination of thymoma and pure red cell aplasia of bone marrow (PRCA), of which seven women were between 44 to 68 years old. The diagnosis of PRCA was established before the detection of thymoma in 1 patient, simultaneously in 3, after - in 4. Seven patients underwent timomectomy. The weight of removed thymomas was from 200 to 780 grams. Morphological type A thymoma variant (spindle cell) was installed in 2 patients, type B1 - in 2, type B2 - in 2, type B3 - in 2. Complete remissions were obtained using cyclophosphamide and cyclosporin in 5 patients, lasting from 6 months to 7 years. The results of immunological studies with the identification of non - hemolytic antibodies to the proteolytic antigen (Pr1d) on the erythrocyte membrane in 4 patients are presented. Of these, two studied patients simultaneously detected antibodies to the Pr1d antigen and the interspecific antigen of mammalian erythroblasts (IAME). It is shown that the lifespan of red blood cells are not changed. The direct Coombs test was negative in 5 patients, but with the help of aggregate hemaglutination test and enzyme immunoassay, antibodies were detected on the surface of erythrocytes. The pathogenesis of this combination of diseases remains unclear and needs to be elucidated.