Hematology Centers Research Articles

Pharmacoeconomic research of surgical treatment of juvenile nasopharyngeal angiofibroma: preoperative endovascularly occlusion classes

Introduction. Intraoperative control of bleeding during surgical treatment of juvenile nasopharyngeal angiofibroma (JAN) remains controversial. There is no consensus as to the routine use of preoperative embolization, given its high cost and inconsistent availability of the procedure in care centers. There were no publications devoted to the comprehensive pharmacoeconomic analysis of preoperative vascular embolization (PVE) occlusion classes on the surgical treatment of JAN by the time of publication Aim. To evaluate pharmacoeconomic value of preoperative vascular embolization (PVE) occlusion classes (non-embolized, incomplete and complete) on the surgical treatment of JAN.Materials and methods. A total of 139 patients who underwent JNA surgical resection in 2013-2021 time period were identified. All of these patients were treated in National Medical Research Center for Children's Hematology, Oncology and Immunology named after Dmitry Rogachev. We evaluated JNA surgical resection outcomes, length of stay (LOS) with prognostic factors using a multiple linear regression (MLR), cost-per-day (CPD), cost-minimization analysis (CMA), cost-utility ratio (CUR), willingness to pay (WTP) with purchasing power parity (PWP).Results and discusion. Surgical transnasal endoscopic treatment of JAN in the quaternary healthcare center, regardless of the degree of embolization and the presence/absence of intraoperative blood transfusion, is at the willingness-to-pay threshold for the healthcare system of the Russian Federation. The most cost-utility method of treatment remains the absence of embolization (within clips placed in the larger diameter vessels). and the absence of blood transfusion, the least cost-utility method is the incomplete embolization, regardless of the presence/absence of blood transfusion.Conclusion. The results of the pharmacoeconomic study emphasize the high significance of the rejection of routine preoperative vascular embolization of JAN and implementation of standard risk-adapted treatment algorithm for indications of preoperative vascular embolization. Which is particularly important for resource allocations and health policy decision making to increase the efficacy and safety of the JNA treatment.

Management of Nutritional Needs in Pediatric Oncology: A Consensus Statement.

Simple SummaryNutritional management is an underestimated issue in treating pediatric cancer, since a systematic approach is currently lacking. In this consensus statement, a cohort of 12 experts selected from four different tertiary pediatric oncology centers formulated 21 clinical questions regarding the identification and treatment of nutritional issues in children with cancer. These questions were discussed, and practical recommendations were provided. With this paper, we aimed to give consensus-based guidance for addressing the nutritional needs of children with cancer, filling a gap in the field.Malnutrition, intended as both overnutrition and undernutrition, is a common problem in children with cancer, impacting quality of life as well as survival. In addition, nutritional imbalances during childhood can significantly affect proper growth. Nevertheless, there is currently a lack of a systematic approach to this issue in the pediatric oncology population. To fill this gap, we aimed to provide practice recommendations for the uniform management of nutritional needs in children with cancer. Twenty-one clinical questions addressing evaluation and treatment of nutritional problems in children with cancer were formulated by selected members from four Italian Association of Pediatric Hematology and Oncology (AIEOP) centers and from the Survivorship Care and Nutritional Support Working Group of Alliance Against Cancer. A literature search in PubMed was performed; during two consensus meetings, all recommendations were discussed and finalized using the nominal group technique. Members representing every institution voted on each recommendation. Finally, recommendations were approved by all authors.

Clinical profile and demographic characteristics of moderate and severe hemophilia patients in a tertiary care hospital of Bangladesh

BackgroundHemophilia is one of the commonest inherited bleeding disorders which may lead to chronic bleeding tendencies and life-long disabilities if not properly managed. Knowing the pattern of the disease aids in the prevention of disability and improvement of quality of life in hemophilia. However, there is a dearth of literature on the issue in Bangladesh. So, this study was designed to explore the frequency and site of spontaneous bleeding in moderate and severe hemophilia patients visiting in a tertiary level hospital.MethodsThis descriptive cross-sectional study was conducted at the department of Hematology and Bone Marrow Transplantation (BMT) Center in Dhaka Medical College Hospital, Dhaka between February 2020 and August 2020. A total of 44 diagnosed cases of moderate to severe hemophilia were included in the study according to inclusion criteria. A detailed inquiry of history, thorough physical examination and relevant investigations were done and were recorded in case-record form. Informed written consent was taken from patients or their guardians where appropriate. All procedures were done according to Declaration of Helsinki. After entry and checking, data was analysed using SPSS version 26.ResultsOut of 44 participants, 25 (56.8%) and 19 (43.2%) had moderate and severe hemophilia. Mean age of the study population was 21.31 (± 9.78) years with the majority aged between 11 and 20 years (45.5%). All sociodemographic features were similar across severity. Hemophilia A and B was found in 90.9% and 9.1%, respectively. However, all type B patients severe hemophilia making it statistically significantly different from type A (p = 0.029). The median age of first bleeding was 3.5 years and median age of first diagnosis was 5 years. Nevertheless, approximately 67.4% patients were diagnosed as a case of hemophilia at the time of their first diagnosis. The median spontaneous bleedings episodes among all patients was 32 (range: 0–97) which did not different significantly between severe and moderate patients. The most common affected (target) joint was knee joint (88.6%) followed by elbow joint (64%) among all patients. The knee joint was more commonly involved in severe than moderate disease.ConclusionThis study observed the variations in pattern and frequency of spontaneous bleeding in patients with hemophilia. Severe disease was more frequent in hemophilia B than A and knee joint was the most frequent site of bleeding. However, further extensive studies are recommended.

The association between plasma IL-6 levels and several thalassemia-related clinical features in Iraqi patients

The present study was set to investigate the potential association between the level of Interleukin-6 (IL-6), as a key component of the pro-inflammatory response, with different thalassemia’s biological and clinical features. For this purpose, one hundred fifty blood samples were collected from 100 beta-thalassemia patients, who attended the Genetic Hematology Centre at Ibn Al- Baladi Hospital in Baghdad, Iraq, and 50 healthy subjects who were employed as a control group. IL-6 levels were estimated using an ELISA Kit, whereas other thalassemia-related clinical features (such as HbA, HbF, ferritin, blood transfusions, splenectomy status, and the history of frequent infection) were additionally assessed. The results of the present study showed a significant elevation (P≤0.01) in the levels of IL-6 in thalassemia patients as compared to healthy controls (57.7763± 8.94837 vs. 6.3059± 1.90364 pg/ml, respectively). Furthermore, IL-6 plasma levels seem to be influenced by the number of multiple scheduled blood transfusions, with the higher IL-6 mean level corresponding to the more frequent transfusions. Also, splenectomized thalassemia patients showed significantly higher IL-6 levels than those of non-splenectomized patients (61.2687±9.30688 vs. 56.9571±8.71926 pg/ml, respectively).

Long-term follow-up of cladribine treatment in hairy cell leukemia: 30-year experience in a multicentric Italian study

Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24–88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04–28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p < 0.0001). Non-hematological grade 3 or higher early toxicity was reported in 103 (20.1%) patients. Median OS was not reached: 95.3%, 92.4%, and 81.8% of patients were estimated to be alive at 5, 10, and 15 years, respectively. Forty-nine patients died (9.5%), following an infection in 14 cases (2.7%), natural causes in 14 (2.7%), cardiovascular events in 13 (2.5%), a second neoplasm in 6 (1.2%), and progression of HCL in 2 cases (0.4%). Following treatment of HCL with 2CDA, 80% of patients are estimated to be alive 15 years after diagnosis.

Quality of Life of Children age from (8- lessthan13) years with Acute Lymphocytic Leukemia Undergoing Chemotherapy at Hematology Center in Medical City

Objective (s): To assess the QoL of children age from (8- lessthan13) years with acute lymphocytic leukemia undergoing chemotherapy and to find out the relationship between the QoL of children with acute lymphocytic leukemia and their illness history.&#x0D; Methodology: A descriptive study included (40) children with acute lymphocytic leukemia who were ranged between (8 - less than 13 years) at the Hematology Center in Medical City for the period from 4th March 2021 to 1st September 2021. The sample was non-probability (purposive) sample of children (male and female). A questionnaire designed with 2 main parts was used. The first part focused on sociodemographic characteristic for children. The second part, which consisted of four domains, focused on the quality of children with acute lymphocytic leukemia. The data were analyzed by applying statistical methods (descriptive and inferential) that were applied by using SPSS version 20.&#x0D; Results: The study's findings that children aged from 8 to less than 13 years have moderate effects on all domains of the quality of life in which 90% of them are showing a moderate level in the physical functioning domain,70% are showing a moderate level in the emotional functioning domain, in regard to the social functioning domain 52.5% are showing a moderate level and 67.5% of them are showing a moderate level in school functioning domain.&#x0D; Conclusion: According to the finding of the present study, the researchers concludes that acute lymphocytic leukemia is more prevalent in males than females. In children aged 8 to less than 13 years, all domains of quality of life are moderately affected.&#x0D; Recommendations: The study recommended that all children with ALL and their parents get counseling and education programs about leukemia, medical care, efforts to overcome side effects, and nutrition, all of which help to improve the children's quality of life.

Nutritional evaluation of the children and teenagers at the diagnosis time of acute leukemia

Acute leukemia is the most cancer has frequency in children, Malnutrition is one of the common complications of children with cancer, and malnutrition has been identified as a significant factor in treatment tolerance, increased morbidity, poor prognosis, reduced quality of life, and higher healthcare expenses. The study aimed at assessing the nutritional status of children with acute leukemia at diagnosis time before chemotherapy, assess the prevalence of malnutrition in acute leukemia groups compared to healthy groups and find any association between malnutrition and demographic factors such as gender and socioeconomic level. A case-control study was conducted in Karbala city, The case data was collected from Imam Al-Hussain Oncology and Hematology center and a control group was collected from primary health centers in Karbala city. The data was collected over a period of approximately 3 months starting from 2nd January 2022 to the 5th April 2022. The study sample included 140 children (70 cases and 70 controls) whose ages were from (2 to 14) years, The study used convenient sampling (non-random sampling technique) to choose the case and control groups via direct interviews and physical examination.

COVID-19 Disease in Patients with Hematological Disease-Single Center Data

COVID-19 Disease in Patients with Hematological Disease-Single Center Data

The first results of genetic screening and exploration of genotype-phenotype correlations in retinoblastoma patients from Belarus

Retinoblastoma is an aggressive eye tumor originating from maturing cone precursors in the developing retina and most commonly seen in childhood. In 98 % of patients, retinoblastoma is caused by bi-allelic inactivation of the RB1 tumor suppressor gene. Approximately 40 % of disorders in the RB1 gene are germline. This study aimed to analyze the frequency of germline RB1 variants in a cohort of Belarusian patients with retinoblastoma and to correlate the variants with clinical phenotypes. The study was approved by an Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. The study included 20 patients from unrelated families (9 patients with unilateral retinoblastoma, 11 – with bilateral). Two out of eleven patients with bilateral retinoblastoma had a positive family history. Genomic DNA was extracted from peripheral blood mononuclear cells. Using polymerase chain reaction, we obtained fragments including sequences of all exons, regions of splice sites and promoter regions of the RB1 gene. Nucleotide sequences of the obtained amplicons were detected by next-generation sequencing. All clinically significant variants were confirmed by Sanger sequencing. Multiplex ligation-dependent probe amplification (MLPA) or fluorescence in situ hybridization (FISH) were used to detect gross alterations. A genetic analysis of blood relatives was carried out for five probands with detected germline variants. We identified 13 different variants in 14 patients: 38.5 % (n = 5) of them were defects in splice sites; 15.4 % (n = 2) – missense mutations; 15.4 % (n = 2) – small deletions (frameshift); 23% (n = 3) – large deletions; 7.7% (n = 1) – nonsense mutations. Four of these variants had not been previously reported in patients with retinoblastoma from other populations (exon 3: c.350_351delTT, p. Phe117TyrfsTer2; exon 8: c.861+2T&gt;G; exon 24: c.2520+4A&gt;G; Del of exons 16, 17). Germline mutations were detected in 33.3 % (3/9) of patients with unilateral retinoblastoma and in 100% (11/11) of patients with bilateral disease. A genetic screening of relatives showed that three variants were de novo, and two variants were inherited from parents in families with a positive history of retinoblastoma. Here we reported the first results of genetic examination of Belarusian patients with retinoblastoma. Seventy-eight point six per cent (78.6 %) of variants were detected by sequencing, 21.4 % were identified with the help of the MLPA and FISH methods. Among sporadic cases, germline RB1 variants were detected in 66.6 % (12/18) of cases. A full range of screening techniques is required to achieve high sensitivity of detection in retinoblastoma patients. Our study also provides new evidence that will inform patient management and genetic counseling.

P1221: DIFFUSE LARGE B-CELL LYMPHOMA RICHTER SYNDROME IN CHRONIC LYMPHOCYTIC LEUKEMIA – A RETROSPECTIVE ANALYSIS OF TREATMENT OUTCOMES IN POLISH ADULT LEUKEMIA STUDY GROUP

Background: Richter syndrome (RS) is a recognized uncommon manifestation and evolution of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with a dismal prognosis. It occurs in 2-10% of CLL patients. It is associated with a clonal evolution and progression, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL) or, less frequently, to Hodgkin Lymphoma (HL). Despite the advances in understanding pathogenesis of the disease, the DLBCL variant of RS (DLBCL-RS) is associated with a dismal prognosis with a median survival < 1 year. The treatment options and risk factors of worse outcome for RS still need to be further expanded. Aims: To study the characteristic and treatment outcomes of patients with DLBCL-RS. Methods: The retrospective analysis of 99 patients diagnosed with DLBCL-RS treated in hematology centers of the Polish Adult Leukemia Study Group (PALG) between 2011 and 2021. Results: Clinical data of 124 patients with Richter syndrome was collected. Ninety-nine patients were diagnosed with DLBCL-RS (79.8%) and further analyzed. Median time since CLL diagnosis to Richter transformation was 43.0 months (range 0-252.0). At the time of transformation 31.3% patients had CLL Rai stage IV, 74.7% were ECOG< 2, while the median Cumulative Illness Rating Scale (CIRS) was 4 (range 0-16). Thirty-seven patients transformed during CLL treatment, 56.7% of them were receiving novel agents (Brutons tyrosine kinase inhibitor or BCL2 inhibitor). Median time of observation after transformation was 10.7 months (range 0-98.6). Median overall survival (OS) after DLBCL-RS diagnosis was 17.3 months (95% Cl 11.9-46.8) and median progression-free survival (PFS) 13.5 months (95% Cl 9.6-22.7). Seventy-six patients (76.8%) had RS treated with intensive chemotherapy protocols, mainly R-CHOP-like regimens for the first line treatment. Only 42.3% had response to the treatment (25/76 complete responses and 11/76 partial responses). Worth mentioning is that in the group of patients with response two patients had ibrutinib monotherapy and one had rituximab-ibrutinib. In forty patients RS was primarily resistant to administered treatment and 65% of them died due to progression or treatment related complications. In the primary resistant DLBCL-RS p53 pathway aberration was noted in 47.5% of patients (17p deletion in 13 patients or TP53 mutation in 6 patients). Better results were achieved for patients who proceeded to autologous hematopoietic stem cell transplantation (auto-HSCT; n=8) and allogeneic HSCT (allo-HSCT; n=10). The median OS in auto-HSCT recipients was 46.1 months, while in allo-HSCT the median OS reached 18.3 months (3 patients died due to allo-HCST-related complications). Significantly lower OS (3.4 months, 95% Cl 14.13-not reached) was observed for RS in heavily pretreated CLL patients (>3 lines of therapy preceding transformation) compared to those treated with up to 3 lines of therapy (23.7 months) (p=0.0002). Median OS for treatment naïve patients at DLBCL-RS diagnosis was not reached. Other factors identified as predictors of poor OS in univariate analysis were ECOG ≥2 (p=0.0014), hemoglobin level <10 g/dl (p=0.017) and platelet count <100x109/L (p=0.0065). Summary/Conclusion: Our study represents the largest dataset of DLBCL-RS patients in Polish hematology centers and confirms the poor outcomes and prognosis associated with RS. The worst treatment results were observed in RS receiving >3 lines of CLL therapy preceding transformation. Only proceeding to hematopoietic stem cell transplantation may improve the prognosis.

P1569: COVID19 AND ITS IMPACT ON HEMATO-ONCOLOGICAL PATIENTS. DIFFERENCES IN OUTCOMES IN RELATION TO OMICRON CIRCULATION AND VACCINATION STATUS?

Background: COVID-19 has a pleomorphic presentation that goes from asymptomatic patients to critical disease with pneumonitis as the lead complication. Main risk factors for critical illness comprise age, cardiovascular disease and obesity. In Hemato-oncological patients, immune response is impaired due in part to their disease and also oncological treatment. Lethality rates reported for these patients are higher than general population and there is a trend towards a greater impact in patients diagnosed in the last 5 years. Our country has experienced two COVID-19 waves since the first cases in march 2020. There is national evidence of less Iethality and critical cases with omicron circulation Aims: To present an interinstitutional registry of COVID-19 patients with underlying hemato-oncological diseases. Methods: We included patients with hemato-oncological diseases assisted at Hospital de Clínicas and Hospital Maciel from Montevideo Uruguay, who were diagnosed with COVID-19 between march 2020 to February 2022. Risk factor presence was established as one of the following: age older than 60, cardiovascular disease and obesity. Full vaccination was defined as two doses and 14 days after last injection. Omicron circulation refers to the period between December 2021 and February 2022 when Omicron variant was responsible for more than 99% of cases in Uruguay. Results: 110 patients were included with a median age of 53 years. Diagnosis comprises 51.8% (n=57) chronic lymphoprolipherative diseases, 20% (n=22) monoclonal gammapaty, 14.5% (n=16) chronic myeloprolpherative diseases, and 13.6% (n=15) acute leukemias and myelodysplastic syndromes. A 34.5 % of the patients were fully vaccinated. Hospital admission was required in 23.6% and there was 14.5% of critical cases. Global lethality rate was 14.5% (n=16), higher than global lethality reported for Uruguay in the same period (0.84%, with a total of 815704 infections). Figure 1 shows data adjusted by disease, illness status, hospital admission, risk factors, vaccination status, and omicron circulation. Requirement of hospital admission, and presence of risk factors were associated with higher lethality (p=0.0001. and p=0.0022), whereas active disease was associated with more lethality but with no statistical difference (p=0.058). Lethality was inferior in full vaccinate state (5.3% vs.19.4%), but with no statistical difference (p=0.0504). Our data reveals a trend towards inferior lethality during omicron wave (9% vs 18%), however not statistical difference was shown. Image:Summary/Conclusion: We present an interinstitutional registry from the main hematologic public centers in Uruguay. Patients included present a broad spectrum of hemato-oncological diseases. The proportion of vaccinated patients is significantly inferior to general population in our country (34.5% vs. 77.1%). Admission requirement and presence of risk factors were associated with higher lethality. Although full vaccination and omicron circulation seem to be associated with inferior lethality, difference was not statistically significant. That may be in relation to the number of patients included and ought to be evaluated prospectively. COVID-19 outcomes in hemato-oncological patients are substantially inferior to general population and our data suggest that impact is greater in patients with active disease. We believe that hemato-oncological patients constitute a vulnerable population in regards to COVID-19 justifying solid directed actions such as booster vaccination.

PB1792: NGS VS PCR FOR THE DETECTION OF NPM1 GENE MUTATIONS IN ACUTE MYELOID LEUKEMIA.

Background:NPM1 gene mutations are found in 30% of acute myeloid leukemia (AML) cases. It is a reliable marker for the evaluation of therapy outcome and minimal residual disease (MRD) monitoring. The most often mutations are 4bp insertions in exon 12, affecting 2 functionally important tryptophan residues (W288 and W290) in the C-terminal region of nucleophosmin and causing a frameshift. As a result, a leucine-rich motif (L-xxx-V-xx-V-x-L) is formed, which is a signal sequence for protein export from the nucleus to the cytoplasm. Commonly NPM1 gene mutations are detected by fragment analysis (FA) of PCR fragment of 12 exon for the presence of 4bp insert. Alternatively, allele-specific polymerase chain reaction (AS-PCR) to detect inserts belonging to the A, B, or D type (representing up to 90% of all inserts) is used. However, about 10% remaining cases are non-standard inserts and intron polymorphisms that require more precise evaluation. Aims: Evaluation of diverse approaches for efficient NPM1 gene mutation analysis and their robustness for the diagnostics. Methods: The study included 80 DNA samples from AML patients admitted to the National Research Center for Hematology in 2019-2021 that were positive for NPM1 gene mutations detected by FA performed with the Nanophor-5 genetic analyzer (Synthol, Russia). The type of insert was assessed by AC-PCR. Samples in doubt were evaluated by targeted next-generation sequencing (NGS) on MySeq (Illumina, USA). Results: In 62 out of 80 samples, the type of insert (A, B, or D) was reliably determined by AS-PCR. In 9 cases type of insert was not detected. In further 9 cases, amplification ΔCt between wild-type and mutant allele was out of reliable range. These 18 samples were examined by NGS, and 2 out of 18 showed an intron deletion, which, presumably, does not affect the function of the protein, but leads to the appearance of an additional peak on FA. In 16 out of 18 samples, non-standard inserts were detected (Table 1). Type A inserts were found in 48 out of 78 cases (61.5%), type B - in 2 out of 78 (4.5%), and type D - 15.4% (12 out of 78). We have detected atypical inserts in 16 out of 78 cases (20.5%), which is more than reported in the literature. 14 out of 16 atypical inserts result in a leucine-rich motif, as do standard inserts. In 4 out of 16 cases, one of the 2 functionally important tryptophan residues was retained (W280), therefore possibly conserving nuclear localization signal. The effect of partial preservation of the nucleolar localization of nucleophosmin on prognosis in AML has not been studied yet. Image:Summary/Conclusion: FA is still a golden standard for screening NPM1 gene mutations in AML. AS-PCR could be effectively used for monitoring cases with standard inserts. However, NGS greatly facilitates non-standard inserts identification, appropriate allele-specific primers design for MRD analysis, and avoiding false-positive FA results for cases with intron localization of the insert.

PB2257: SARS-COV-2 VARIANTS DETECTED IN EMPLOYEES OF ONE MEDICAL CENTER

Background: March 2020 strict measures were introduced at the National Research Center for Hematology (Moscow, Russia) in order to prevent the spread of SARS-CoV-2: the mandatory wearing of masks, screening for the presence of symptoms of acute respiratory viral infections, regular PCR testing of all staff and patients, a ban on visiting patients, and cancellation of all face-to-face meetings of the employees. Nevertheless, in the fall of 2020, an outbreak of the disease among employees was detected in the institution. Aims: To study the variety of SARS-CoV-2 variants infecting employees during the outbreak and to reveal possible transmission routes. Methods: The study included 42 employees infected during the 09/17/2020 - 01/01/2021 outbreak, which corresponded to the 2nd wave of COVID-19 worldwide. PCR testing for the detection of SARS-CoV-2 RNA in nasopharyngeal samples from the staff of the center was performed using the PCR-RV-2019-nCov kit (Syntol, Russia). Sequencing of SARS-CoV-2 samples was performed by the NGS method using the QIAseq SARS-CoV-2 Primer Panel kit (Qiagen, USA); the raw data were analyzed according to the HAVOC protocol (DOI 10.1186/s12859-021-04294-2). Results: Only 4 (10%) out of 42 employees had a positive PCR test result while having COVID-19 symptoms, the rest - during routine screening. The course of disease was characterized as asymptomatic in 2 (5%), mild in 28 (86%), moderate in 3 (7%), severe in 1 (2%), extremely severe was not detected. Based on sequencing data, we identified 5 different variants of SARS-CoV-2 found in 2 or more samples. Four of them were found each within only one clinical department and did not occur outside of it. Variant 1 was first detected in an asymptomatic carrier on 10/29/2020 and again on 11/2/2020 simultaneously in 8 employees during routine testing (a total of 13 cases were registered in one department). This type was distinguished by the presence of 5 missense mutations in the Spike region, which may have been the reason for its high contagiousness. Among these 13 employees, 1 (7%) had a severe infection, 2 (14%) had a moderate infection, 9 had a mild course (1 had a cutaneous form), and 1 (7%) had an asymptomatic infection. Variant 2 was detected in 2 carriers, variants 3, 4 - in 3, with an interval of a week. Variant 5 was identified in 4 employees from 2 departments (2 people in each from 10/8/2020 to 10/26/2020). For these employees, the course of COVID-19 was characterized as mild. Also, 3 pairs of similar variants were identified, however, the lack of complete similarity and a large time interval raises doubts about their connection. All other 11 SARS-CoV-2 nucleotide sequences were unique. Summary/Conclusion: Anti-epidemic measures taken at the center have shown effectiveness in reducing the spread of nosocomial infection. The identified clustering of virus variants indicates the predominant infection of employees within departments. The obtained clinical data do not make it possible to identify associations of a particular SARS-CoV-2 variant with the course of the disease. Sequencing of SARS-CoV-2 samples allowed for an epidemiological study and identification of a variant that is likely to be highly contagious.

PB1998: WEEKLY OPPOSED TO BI-WEEKLY BORTEZOMIB AS PART OF INDUCTION CHEMOTHERAPY IN NEWLY DIAGNOSED MULTIPLE MYELOMA IS BETTER TOLERATED AND EQUALLY EFFICIENT: REAL-WORLD DATA FROM A RETROSPECTIVE AUDIT

Background: The VTD (Bortezomib, Thalidomide, Dexamethasone) triplet chemotherapy regime is frequently used as induction chemotherapy in newly diagnosed multiple myeloma prior to autologous stem cell transplant. The manufacturer’s protocol recommends a twice-weekly dosing schedule. Adverse effects are common, most notably neuropathy and cytopenias. These can be disabling and are often permanent, with significant impacts on quality of life. This limits drug tolerance with management confined to dose reduction or discontinuation. A once-weekly dosing schedule has been widely adopted, but to date, no clinical trials have been conducted to compare the efficacy and side effect profile of this dosing frequency in transplant-eligible myeloma. Aims: In order to investigate prescribing practice locally, we conducted a retrospective audit in Leicester Royal Infirmary, a tertiary Haematology centre in the UK. Primary outcomes were response to induction therapy, and the development of neuropathy (peripheral or autonomic) or serious adverse events occurring whilst on VTD. Secondary outcomes included cumulative Bortezomib dose, number of Bortezomib cycles and Thalidomide tolerance. Methods: Real-world data was collected consecutively from all patients treated in the intensive treatment arm with VTD as first-line chemotherapy between January 2015 and November 2020. Patient received Bortezomib 1.3mg/m2 subcutaneously on days 1,4,8 and 11 of a 21-day cycle (bi-weekly) or days 1,8,15 and 22 of a 35-day cycle (weekly). The trust protocol was altered in December 2020, increasing the bi-weekly regime to a 28-day cycle Results: We demonstrate a trend of lower incidence of neuropathy, both peripheral and autonomic, with the weekly regime (PN≥2: weekly 8.7% bi-weekly 19.6% AN: weekly 8.7% bi-weekly 26.5%). There was also a trend of fewer serious adverse events with lower rates of hospital admissions due to infection (weekly 33.3% bi-weekly 47.8%). Patients on the weekly regime received more VTD cycles and a higher cumulative dose (p=0.044). The initial therapeutic response between the two regimes were similar (weekly: ORR 87% ≥VGPR 78.3%, bi-weekly: ORR 86.3% ≥VGPR 60.8%). Preliminary data from patients treated with bi-weekly Bortezomib in a 28-day cycle shows lower rates of peripheral neuropathy compared to the 21-day cycle. Image:Summary/Conclusion: Here we demonstrate that weekly Bortezomib is better tolerated with equal efficacy in terms of initial therapeutic response. We believe that delivery of Bortezomib through a weekly regime facilitates patients being able to maintain on Bortezomib longer and receive higher cumulative doses. This may have important implications in those later deemed unsuitable or transplantation and for future treatment as intolerance or refractoriness limits the ability to obtain Bortezomib in further treatment lines. Preliminary data shows the cycle length may also be important in determining the risk of side of side effects and we intent to continue to monitor patients treated with this regime.

P677: CLINICAL EFFICACY AND TOLERABILITY OF VENETOCLAX PLUS RITUXIMAB IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA – REAL WORLD ANALYSIS OF POLISH ADULT LEUKEMIA STUDY GROUP

Background: The introduction of venetoclax into clinical practice has improved the outcome of patients with relapsed/refractory chronic lymphocytic leukemia (RR-CLL). The results of the MURANO trial published in March 2018 showed significantly longer progression-free survival (PFS) and overall survival (OS) in RR-CLL patients treated with venetoclax and rituximab (VEN-R) comparing to bendamustine and rituximab (BR) and resulted in the approval of VEN-R in the therapy of RR-CLL in the European Union and the United States. It should be noted that the results of registration studies often do not correspond with the data from real-life observations. Aims: To study the clinical efficacy and safety profile of VEN-R treatment in RR-CLL patients outside clinical trials. Methods: We performed retrospective analysis of RR-CLL patients treated with VEN-R in hematology centers of the Polish Adult Leukemia Study Group (PALG) from 2019 to 2021. Results: Clinical data of 117 RR-CLL patients treated with VEN-R were collected. Median patient age upon initiation of VEN-R therapy was 67 years (range 33 – 84 years). Seventy-two patients (61.5%) were men. Median Cumulative Illness Rating Scale (CIRS) was 6 (range 2 - 16). Patients were treated with a median of 2 (range 1–9) previous lines of therapy, whereas 32 patients (27.4%) had relapsed following the first line of treatment. Overall, 25 patients (21.4%) had 17p deletion, whereas TP53 mutation was identified in 13 patients (11.1%). The median follow-up was 9.96 months (range 0.27 - 29.13). The overall response rate (ORR) was 95.2%. Seventeen patients (14.5%) achieved complete remission (CR), 83 (70.9%) partial remission (PR), while in 5 patients (4.3%) disease progression was noted. In the patients with 17p deletion (n=22) or TP53 mutation (n=11), CR and PR were observed in 4 (12.1%) and 29 (87.9%) patients, respectively. The median PFS in the whole cohort was 20.8 (95% CI 18.43 - not reached) months and the median OS was not reached. In our study none of the analyzed clinico-pathological factors had significant impact on ORR, PFS and OS. During the follow-up time four (3.4%) cases of Richter transformation were diagnosed. There were 18 deaths recorded during the course of observation; 3 (16.7%) due to disease progression and 7 (38.9%) due to COVID-19 infection. The others were due to infections other than SARS-CoV-2 (n=3, 16.7%) and the cause of death could not be specified in five cases (27.8%). Eighty-three patients (70.9%) remain on treatment, while treatment was discontinued in thirty-four cases (29.1%). Reasons for therapy discontinuation included patient’s death (52.9%), treatment-related cytopenias (17.6%), disease progression (14.7%), Richter’s transformation (11.8%), autoimmune hemolytic anemia (5.9%), diarrhea (2.9%) and infections (8.8%). In one case treatment discontinuation was due to consent withdrawal and one patient was lost to follow-up. The following adverse events of VEN-R treatment were reported during the study: all grade neutropenia (71.8% with grade 3/4 in 55.6%), anemia (51.3%), thrombocytopenia (47%), pneumonia (9.4%), neutropenic fever (6.8%), autoimmune hemolytic anemia (4.3%), immune thrombocytopenic purpura (1.7%), diarrhea (4.3%) and in one case exacerbation of heart failure was observed. Summary/Conclusion: In this retrospective analysis the outcomes of treatment with the VEN-R regimen in real-life setting were worse than those reported in the MURANO trial.

Study of some immunological parameters in hematological malignancies patients

This study aimed to verify the number of differentiation aggregates that include HLA-DR, CD5 and CD7 In patients with hematological malignancies and comparing them with the healthy group, where the levels of these subgroups were detected in the peripheral blood of 40 males and females, Where samples were collected by 20 samples from patients with malignant hematomas, Plus 20 people from the healthy group.All blood samples and available data were collected from patients with hematological malignancies, from the Center for Oncology and Hematology,in partnership with the laboratories of medical centers and Al-Jawadeen National Laboratory, for the period from November 2021 to May 2022.The immunophenotypes of HLA-DR, CD5 and CD7 were studied in the samples using the flow cytometry technique,where the rate of differentiation aggregates in patients with leukemia was much higher than in healthy people, where the results showed significant differences with statistical significance at the level of P≤ 0.05 in the proportion of CD5, CD7 and HLA-DR in samples of patients with hematological malignant diseases, and a slight increase in the level of CD5 and HLA-DR was found in males than in females, and a slight decrease in the level of CD7 was observed in males than in females.

EVALUATION OF BLOOD AND BLOOD PRODUCTS QUALITY AT CENTER FOR HEMATOLOGY - BLOOD TRANSFUSION, HAI PHONG VIETNAM - CZECH FRIENDSHIP HOSPITAL

The objective of research: Study the status of blood quality and blood products in Haiphong Hematology and blood transfusion Center in 2019.The subject of research: Whole blood units, erythrocyte volume, fresh frozen plasma, removed coagulation plasma, platelet volume pool, cold-clotting factor VIII. Method of research: Cross-sectional study. Results of research: The quantity of the blood production: erythrocyte volume produced from whole blood 250 ml and 350 ml that has hemoglobin amount 31.5 ± 4.9 g/unit and 43.5 ± 5.2 g/unit respectively. Fresh-frozen plasma has factor VIII concentrations is 1.86 ± 0.43 IU/ml, the amount of fibrinogen is 0.76 ± 0.03 mg/Unit and protein is 73.8 ± 6.1 g/l and the remained amount of white blood cells markedly reduced. Platelet volume pool has platelet numbers is 1.92 ± 0.4 × 10 11/unit. Cold-clotting factor VIII, that has factor VIII concentration is 325 ± 14 IU/unit, fibrinogen is 90 ± 1.6 mg/Unit

Spectrum of concomitant brain vascular lesions in pediatric diffuse gliomas

Cerebrovascular disease represents a threatening factor for brain cancer survivors. However, a comprehensive evaluation of small vessel disease related to gliomas has not yet been performed. This study aims to characterize concomitant vascular lesions in pediatric diffuse gliomas and identify their association with the molecular subgroup of tumors. We performed a retrospective pathological study of biopsy samples of 77 pediatric patients with diffuse gliomas, treated in Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. Eight molecular subgroups were identified by immunohistochemical and cytogenetic studies (H3K27mut, ALT, IDH1mut, BRAFmut-PXA, FGFR1, BRAFmut/FGFR2, RTK, MYB). In each group microvessel density/area (MVD/MVA), tumor vessels co-option and signs of small vessels disease (SVD) were determined. The levels of microvascularization significantly differed between the molecular subgroups of diffuse gliomas, indicating the presence of intrinsic pro-angiogenic activity there. The highest values of MVD/MVA, as well as rate of hemorrhagic necrosis, were found in the BRAFmut/FGFR2, RTK groups. SVD was common in the adjacent tissues of gliomas and occurred in 32.5 % of cases. High grade SVD was associated with the BRAFmut/FGFR2 and IDH1mut subgroups. BRAFmut/FGFR2 tumors were more aggressive and caused cortical microinfarctions in 84,6 % and leukoaraiosis in 87.5 % of cases. IDH1mut tumors were mainly linked with cortical microinfarctions (60 % of cases). The results of the study suggest that concomitant small vascular lesions are common in adjacent tumor tissue and can significantly influence the overall rate of cerebrovascular disease in convalescents with diffuse gliomas.

Risk factors among patients with ovarian cancer attending oncology hematology center in Basrah city

Worldwide, approximately 225,500 ovarian cancers are diagnosed annually . The leading cause of gynecological cancer death (140,200 worldwide annually) is the ovarian cancer, which accounts for more deaths than all the other gynecological cancers combined. The ovarian cancer is the fourteenth commonest cancer among population in Basrah city in Iraq. Methods This is a case control study carried out in the Basrah oncology –hematology center and primary health care centers in Basrah city . The study include 103 cases of ovarian cancer and 206 control. Result we found that more than half of case of ovarian cancer aged 50 years and above. History of insulin treatment is a risk factor for ovarian cancer (OR more than one) with significant statistical association. Hysterectomy and tubal ligation are protective against ovarian cancer . Conclusion There are many risk factors of ovarian cancer some of these are modifiable while the others are not modifiable. Hysterectomy and tubal ligation considered as protective factors.

The impact of COVID-19 and armed conflict on cancer care in Armenia: A cross-sectional study.

e18551 Background: The COVID-19 pandemic has interrupted the spectrum of cancer services, exposing vulnerable cancer patients to significant risks. In Armenia, the negative effect of the pandemic was amplified by the Nagorno-Karabakh war in September-November 2020. We explored the combined impact of the COVID-19 pandemic and armed conflict on cancer care provision in Yerevan, Armenia. Methods: We carried out a cross-sectional survey among all oncologists, nurses, and clinical residents (n = 123) actively providing cancer care to adults and children since 2019 at three publicly-funded institutions in Yerevan, Armenia, namely the National Center of Oncology, Hematology center after prof. R.H.Yeolyan, and Mikaelyan Institute of Surgery. Data collection was conducted between November 1 and December 27, 2021. The survey included 71 items assessing institutional characteristics, COVID-19 diagnoses, disruptions to care, adaptations of care, and availability of human and material resources. Descriptive statistics were used to analyze responses from 89 participants (72%). Results: Disruptions to cancer care during the COVID-19 pandemic were reported due to staff absenteeism (16%) and lack of access to cancer treatment [chemotherapy (14%), radiotherapy (7%), surgery (7%)], elective surgery (27%), intensive care services (10%), diagnostic examinations (3%), and inpatient beds (6%). Shortages of clinical staff for pediatric cancer care were noted by 40% of respondents and were mainly attributed to COVID-19 infection (53%) or self-isolation due to testing positive for COVID-19 (25%). Half of the respondents reported suboptimal cancer patient care and outcomes (e.g. delayed diagnosis and treatment, complications of treatment, elevated mortality rates) caused primarily by the de-prioritization of cancer services during the COVID-19 pandemic. The main issues reported by the respondents during the armed conflict were delays in elective surgery (36%) and staff shortages (17%). Confirmed cases of COVID-19 among patients were reported by respondents as: &lt; 10 (by 6% of respondents), 11-50 (36%), 51-100 (27%) and &gt; 100 (7%). Ten respondents (11%) reported that colleagues had died after contracting COVID-19. Twenty-six percent of respondents reported that the overall rate of hospitalizations decreased during the pandemic and 12% reported increased use of telemedicine. Reductions in material resources were reported by 18% of respondents, while 15% reported funding cuts to their unit by the institution. Conclusions: The COVID-19 pandemic and concurrent armed conflict led to disruptions in cancer care in Armenia, resulting in suboptimal care and outcomes for cancer patients. These findings emphasize the need for proactive planning to maintain standards of cancer care delivery in times of societal crises.