Benign Hematologic Disorders Research Articles

Diagnosis and typing of leukemia using a single peripheral blood cell through deep learning

AbstractLeukemia is highly heterogeneous, meaning that different types of leukemia require different treatments and have different prognoses. Current clinical diagnostic and typing tests are complex and time‐consuming. In particular, all of these tests rely on bone marrow aspiration, which is invasive and leads to poor patient compliance, exacerbating treatment delays. Morphological analysis of peripheral blood cells (PBC) is still primarily used to distinguish between benign and malignant hematologic disorders, but it remains a challenge to diagnose and type these diseases solely by direct observation of peripheral blood(PB) smears by human experts. In this study, we apply a segmentation‐based enhanced residual network that uses progressive multigranularity training with jigsaw patches. It is trained on a self‐built annotated dataset of 21,208 images from 237 patients, including five types of benign white blood cells(WBCs) and eight types of leukemic cells. The network is not only able to discriminate between benign and malignant cells, but also to typify leukemia using a single peripheral blood cell. The network effectively differentiated acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (non‐APL), achieving a precision rate of 89.34%, a recall rate of 97.37%, and an F1 score of 93.18% for APL. In contrast, for non‐APL cases, the model achieved a precision rate of 92.86%, but a recall rate of 74.63% and an F1 score of 82.75%. In addition, the model discriminates acute lymphoblastic leukemia(ALL) with the Ph chromosome from those without. This approach could improve patient compliance and enable faster and more accurate typing of leukemias for early diagnosis and treatment to improve survival.

BN SO31 - Pedicle First; a Paved Laparoscopic Approach for Huge Splenomegaly

Abstract Background Since its introduction for the first time by Delaitre et al1 in 1991, laparoscopic splenectomy (LS) has become the minimal invasive approach of choice for the management of the hematological splenic disorders2. Many agreed benefits have been achieved with this approach regarding the hospital stay, blood loss, duration of recovery, aesthetic results and quality of life; however, massive spleens remain a real technical challenge in front of achieving those benefits. The complex and non-typical variable configurations of the vascular system for the pancreatic body and tail which come from the splenic artery represents another faced point of anatomical complications3. Method From March 2020 to February 2024, a prospective study has included 30 patients presented with benign hematological disorders and massive splenomegaly (more than 20 cm longitudinal axis) who underwent laparoscopic splenectomy in our institution. Detailed data regarding their demographics, splenic size, operative time, blood loss, conversion rate, postoperative serum amylase and hospital stay were collected. Standardized anterior approach operative steps were adopted by the same surgeon for all patients with early control of the arterial system of the splenic circulation before mobilization (short gastric vessels and splenic artery 2 to 4 cm away from hilum). Results Thirty patients presented with huge splenomegaly have underwent laparoscopic splenectomy with a conversion rate of 6.6% (2 patients due to extensive perisplenic adhesions). The mean longitudinal splenic dimension was 24 ± 1.5 cm (range from 20 to 27 cm), mean operative time was 110 ± 16 minutes, mean operative blood loss was 160 ± 20 ml, mean hospital stay was 4 ± 1.5 days, postoperative rate of hyperamylasemia in 20% (asymptomatic 6 patients with no operative evidence of pancreatic injury), respiratory complications in 16.6 % (5 patients), and reactive thrombocytosis in 6.6% (2 patients). Conclusion Early laparoscopic control of the arterial system away from the splenic hilum can enable us to lessen the conversion rate for massive splenomegaly patients and achieve successfully the benefits of laparoscopy for those patients on the expense of the elevated postoperative hyperamylasemia rate.

Pelger-Huët Anomaly (PHA) Case Report

Pelger-Huët anomaly is a rare benign hematological disorder. It was first described in the 1920s. It is inherited in an autosomal dominant manner. Nuclear hypolobulation, which can also be seen in other leukocytes, especially neutrophils, is a characteristic feature. This morphological change does not cause a defect in the immune system. It should be differentiated clinically from pseudo-Pelger-Huët anomaly (PPHA). In this study, Pelger-Huët anomaly is presented which is noticed in the peripheral smear of a 22-year-old female patient who came to the hematology outpatient clinic due to her sibling having Hodgkin’s lymphoma. The family members of the case were also evaluated in this respect.

Diagnostic Significance and Association of Reticulin Fibrosis in Benign Hematologic Disorders

Diagnostic Significance and Association of Reticulin Fibrosis in Benign Hematologic Disorders

P-364 Impact on fertility outcomes in survivors after hematopoietic stem cell transplantation for benign and malignant hematologic disorders: a systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility after hematopoietic stem cell transplantation (HSCT) in females and males up to the age of 1 year? Summary answer The overall prevalence of infertility (95% CI) in women treated with HSTC is 64% (0.58-0.70) and in men 39% (0.31-0.47). What is known already HSCT is a well-established treatment that has significantly increased survival in haematological malignancies and also benign diseases since its introduction in the 1980s. The use of high-dose chemotherapy and radiotherapy, myeloablative conditioning, combined with HSCT exposes serious long-term complications, including gonadal dysfunction and infertility. The risk of ovarian and testicular damage seems to be very high. Therefore, the European Society for Blood and Marrow Transplantation (EBMT) had recommended in 2015 to consider fertility preservation measures in children and adolescents requiring HSCT. However, the data on which this recommendation was based was limited and heterogeneous. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search was conducted in Medline, Embase and Cochrane in November 2023, considering papers published since 2000. Participants/materials, setting, methods A total of 1632 records were identified for abstract screening. Only females and males without recurrent disease and follow up of more than one year were considered. For the systematic review, 68 studies fulfilled the criteria. For the meta-analysis, studies with < 10 patients were excluded. Infertility was defined in females as very low AMH, hypergonadotropic hypogonadism, amenorrhoea and/or need for hormone replacement therapy and in males as low inhibin B and/or azoospermia. Main results and the role of chance In total, 68 out of 1632 studies were included in the final analysis. Malignant diseases were mainly acute myeloid / lymphoblastic leukemia, chronic myeloid leukemia/ lymphocytic leukemia and non-hodgkin’s and hodgkin’s lymphoma. Benign diseases were sickle cell disease, Fanconi anaemia, and β-thalassemia major. In the meta-analysis, 56 studies were included, comprising 1853 female malignant cases, 241 female benign cases, 1871 male malignant cases, and 226 male benign cases. The analysis, employing a random-effects model for estimating prevalence and its 95% confidence interval, revealed that the overall pooled prevalence of infertility exceeded 30% in all groups. The prevalence of infertility was highest in female malignant cases (65%, 95% CI: 0.58-0.71). In women with benign diseases it was 61% (95% CI: 0.48-0.73). In males with malignant diseases it reached 41% (95% CI: 0.32 to 0.51) and with benign diseases 31% (95% CI: 0.19 to 0.46). Heterogeneity of data was high as shown by female as shown by the malignant cases of 83% and benign cases of 65% in women and the malignant cases of 91% and benign cases of 74% in males. Limitations, reasons for caution The heterogeneity of the included studies due to treatment variations and diverse characteristics of the study populations with large age ranges, did not allow further subgroup analyses. Thus, an individual and reliable fertility prognosis is still difficult to give. Wider implications of the findings The results of this meta-analysis support the clinical necessity of fertility preservation counselling in females and males undergoing HSCT treatment. Further prospective studies addressing the individual impact of the HSCT treatment on gonadal function are needed Trial registration number The study protocol was registered at the international Prospective Register of Systematic Reviews, PROSPERO (Registry number CRD42023486928).

Investigation of HLA susceptibility alleles and genotypes with hematological disease among Chinese Han population.

Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance.

Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT

Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism. To attempt broader international consensus, a panel of adult and pediatric physician transplant experts was assembled from European Society for Blood and Marrow Transplantation (EBMT), ASTCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), and Asia-Pacific Blood and Marrow Transplantation (APBMT). Consensus was defined as ≥70% of voting members strongly agreeing or somewhat agreeing with a definition. With few exceptions, there was a consensus to endorse the prior ASTCT definitions. Importantly, we revised existing EBMT and CIBMTR data collection forms to align with these harmonized definitions that will facilitate research and international collaboration among transplant researchers and across transplant registries.

Co-existence of hematological disease in cardiac patients presented with chest pain

Abstract Introduction The important association between hematological disorders and cardiovascular system originates within multiple points of interface, ranging from heart and its structural constituents, coronary arteries and veins, cerebrovascular, pulmonary and peripheral vasculature. Any anomaly of either of the blood components can severely affect the blood flow and blood viscosity which finally leads to thrombosis. Objective This study will help clinicians to evaluate those patients having hematological abnormality and are having potential prothrombotic state due to abnormal hemostasis. Rationale Introducing cardiac health screening in patients with any hematological disease can improve the quality of life of these patients. Material and methods This cross sectional analytical study was conducted in hematology Department of Peshawar institute of Cardiology after approval from hospital ethical and research committee. Study duration was 6 months. All patients were subjected to detailed history, clinical examination. Demographic (Age, Gender) and relevant clinical information. Investigation like CBC, coagulation profile, hemolytic profile, Chest X-ray, ECG, Echo, Angiography findings were used to monitor patient’s clinical status. Results Out of 43 patients, 08 cases (18.60%) presented were of benign hematological disorder and the rest 35 cases (81.40%) presented with malignant hematological disorders. A significant P- value of (0.000) was observed in patients with malignant hematological disorder in association with benign hematological disorders. Conclusion From our study findings, several local and international platforms data, it can be concluded that those hematological abnormalities which have direct or indirect association with thromboembolic events can present with cardiac manifestation in the form of chest pain or acute myocardial injury at any stage of disease process. Therefore, clinicians must evaluate patients having hematological abnormality and are having potential prothrombotic state due to abnormal hemostasis for cardiac manifestation of the disease as well.

Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Hematopoietic Cell Transplantation and Cellular Therapies: A Retrospective Monocenter Real-Life Analysis.

(1) Background: Autologous, allogeneic hematopoietic cell transplantation (HCT) and other cellular therapies, including CAR T cell and gene therapy, constitute a cornerstone in the management of various benign and malignant hematological disorders. Invasive fungal infections (IFD) remain a significant cause of morbidity and mortality in HCT recipients. Therefore, we investigated the prevalence and risk factors of IFD following HCT and other cellular therapies in an era of novel antifungal prophylaxis. (2) Methods: In this study, we retrospectively enrolled adult HCT recipients who were treated at our JACIE-accredited center according to standard operating procedures over the last decade (2013-2022). (3) Results: 950 patients who received cellular therapies were studied. None of the 19 CAR T cell and neither of the two gene therapy recipients developed IFD whereas 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Overall, 11 patients who received allogeneic HCT experienced probable IFD, possible IFD was found in 31/473, and IFD was proven in 10/473. A second IFD episode was present in three patients. Four-year OS was significantly lower in proven compared to probable IFD (p = 0.041) and was independently associated with HCT-CI (p = 0.040) and chronic GVHD (p = 0.045). (4) Conclusions: In this real-world cohort, the prevalence of proven and probable IFD in an era of novel antifungal prophylaxis was found to be relatively low. However, IFDs were associated with poor outcomes for patients who received allogeneic HCT.

Digital assessment of peripheral blood and bone marrow aspirate smears.

The diagnosis of benign and neoplastic hematologic disorders relies on analysis of peripheral blood and bone marrow aspirate smears. As demonstrated by the widespread laboratory adoption of hematology analyzers for automated assessment of peripheral blood, digital analysis of these samples provides many significant benefits compared to relying solely on manual review. Nonetheless, analogous instruments for digital bone marrow aspirate smear assessment have yet to be clinically implemented. In this review, we first provide a historical overview detailing the implementation of hematology analyzers for digital peripheral blood assessment in the clinical laboratory, including the improvements in accuracy, scope, and throughput of current instruments over prior generations. We also describe recent research in digital peripheral blood assessment, particularly in the development of advanced machine learning models that may soon be incorporated into commercial instruments. Next, we provide an overview of recent research in digital assessment of bone marrow aspirate smears and how these approaches could soon lead to development and clinical adoption of instrumentation for automated bone marrow aspirate smear analysis. Finally, we describe the relative advantages and provide our vision for the future of digital assessment of peripheral blood and bone marrow aspirate smears, including what improvements we can soon expect in the hematology laboratory.

Involvement of folate and vitamin B12 deficiency in patients with normocytic anemia.

Deficiencies in folate (FA) and vitamin B12 (VB12) are causes of macrocytic anemia. However, in clinical practice, FA and/or VB12 deficiency can occur in patients with normocytic anemia. This study aimed to determine the prevalence of FA/VB12 deficiency in patients with normocytic anemia and the importance of vitamin replacement therapy in these patients. We retrospectively reviewed electronic medical record information of patients whose hemoglobin and serum FA/VB12 concentrations were measured at the Department of Hematology (N=1,388) and other departments (N=1,421) of Fujita Health University Hospital. In the Hematology Department, 530 (38%) patients showed normocytic anemia. Of these, 49 (9.2%) had FA/VB12 deficiency. Twenty of 49 (41%) patients had some hematological malignancies and 27 (55%) had benign hematological disorders. Of the nine patients who received vitamin replacement therapy, one showed a partial improvement in the hemoglobin concentration of ≥1g/dL. In the clinical setting, the measurement of FA/VB12 concentrations in patients with normocytic anemia may be useful. Replacement therapy may be a treatment option to consider in patients with low FA/VB12 concentrations. However, physicians need to pay attention to the presence of background diseases, and the mechanisms of this situation require further investigation.

Evaluation of Hem-o-lok clips in controlling the splenic pedicle in laparoscopic splenectomy in children

BackgroundSplenectomy is an established therapeutic intervention for benign haematological disorders (BHD) in children. Laparoscopic splenectomy (LS) has become accepted as the preferred alternative to the open procedure. The aim of this study was to evaluate the Hem-o-lok clips in controlling the splenic hilum during laparoscopic splenectomy in children as regards feasibility, safety, operative time, cost, and perioperative complications.MethodsThis study included 27 cases with BHD, from April 2020 to December 2021, who underwent LS. In all patients, the Hem-o-lok clips were used to control the splenic pedicle. Operative time, intraoperative complications, need for conversion, and splenic extraction were reported. Postoperative course, complications, and hospital stay were also recorded. Patients were followed up for 3 months for development of complications and for evaluation of cosmetic appearance.ResultsThe mean operative time, excluding splenic extraction, was 67.04 min. There were 3 intraoperative minor bleeding incidents, all not related to Hem-o-lok application, and they were successfully controlled, with no need for conversion. The mean hospital stay was 1.3 days. We used one cartridge for each case (cost; 686 LE, US $28).ConclusionsThe Hem-o-lok clips are feasible, safe, and cost effective in controlling the splenic hilum during LS in children with benign haematological diseases.

Outcomes of blood and marrow transplantation in children less than 2-years of age

Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative option for children with various malignant and non-malignant diseases. Most reports studied all age groups amongst children. Herein we analyzed our data in children transplanted at or less than 2-years of age. We reviewed medical charts of 618 patients who underwent 666 transplantation at our center between 1993 and 2015. There were 340 boys and 278 girls. Median age was 0.7 years (range 0.04-2). Stem cell source was bone marrow (BM) in 492 (73.9%), unrelated umbilical cord blood (UCB) in 161 (24.2%) followed by peripheral blood stem cell (PBSC) in 13 (2%) patients. Matched siblings were the most common donors (n=356, 53.5%), followed by unrelated (n=161, 24.2%) with haploidentical family member donors in 29 (4.4%) transplants. Disease groups were categorized as benign hematology (Thalassemia, Fanconi, Aplastic anemia etc.), benign neoplasm (Langerhans cell histiocytosis, Hemophagocytic Lymphohistiocytosis etc.), non-neoplasms (metabolic disorders, immunodeficiency disorders etc.) and Leukemia/lymphomas (myeloid and lymphoid malignancies etc.). Cumulative incidence of acute GvHD (I-IV) was 31.5% (n=210) and grade III-IV GvHD was 8.7% (n=58). At median follow-up of 115.1 months, the cumulative probability of overall survival (OS) at 5 years was 70.0%±1.9%. Our mortality rate was 31.2% (n=193). The five-year OS was significantly better in patients transplanted for benign hematological disorders (P=.001). Patients transplanted using BM/PBSC as source of stem cells fared significantly better compared to those in which CB was used (P<.001). Post-transplant graft failure remains the leading cause requiring further transplants in this age group. In conclusion, the cumulative probability of OS at 5 years was about 70.0% for all with an OS of 61% in our haploidentical recipients. Analyzing our institutional data over time has enabled us to develop tentative strategies to minimize transplant related toxicities in very young children who are candidates for allo-HCT.

Risk Factors and Outcome of COVID-19 Infection in Haematological Patients : A Multicenter Retrospective Analysis in Malaysia

Introduction: Hematological patients as immunocompromised hosts are vulnerable to severe COVID-19 infection. Given the significant risk of heightened morbidity and mortality from COVID-19, there is an urgent and critical need to establish its impact in these population. A better understanding of adverse prognostic factors could assist hematologist to tailor appropriate treatment. With this background, our aims were to analyse the outcome of COVID-19 infection and to identify risk factors associated with severity and mortality. Methods: This is a multicenter retrospective observational study with data collected from 6 Malaysian hematological centers. This cohort included patients age ≧ 15 years with hematological diseases who developed PCR-documented SARS-CoV-2 infection from 1st January 2021 to 31st December 2021. Data were collected locally from the 6 participating centers. Anonymized data were centrally processed by a coordinating team in Penang General Hospital. The variables assessed included baseline characteristics, type of hematological diseases, anti-neoplastic therapies, COVID-19 treatments and outcomes. Analyses were generated using R statistical software version 4.1.2. Prognostic factors were analysed using Cox proportional hazard regression analysis. Results: A total of 300 patients (168 males, 132 females) were evaluated. The median age was 51 years (range: 15-85 years). 52% were 50 years old and above. 44% had at least one comorbidity. There were 153 (51%) lymphoid malignancies, 94 (31%) myeloid malignancies and 53 (18%) benign hematological disorders. Non hodgkin lymphoma (26.6%) was the commonest hematological disease followed by acute myeloid leukaemia (16.3 %), acute lymphoblastic leukaemia (9.0%), autoimmune diseases (8.0%) and multiple myeloma (7.0%). Of the 247 patients with malignancy, 55% patients had refractory disease. 104 (42.1%) patients were receiving intensive chemotherapy, 40 (16.2%) low intensity chemotherapy, 25 (10.1%) hypomethylating agent, 22 (8.9%) molecular targeted therapy, 36 (14.6%) supportive care and the remaining 20 (8.1%) were not on active therapy. 19.0% of patients were treated with B cell depleting monoclonal antibody including Rituximab (15.3%), Daratumomab (2.7%) or Blinatumomab (1.0%). Only 24 (8%) patients had prior hematopoietic stem cell transplantation. 34.7% were fully vaccinated prior to COVID-19 infection. 45% of patients developed severe or critical COVID-19 infection based on WHO criteria. Cytokine release syndrome (37%) and organising pneumonia (33%) were the two commonest complications. The median follow up was 158 days (range: 4 - 345 days). The overall mortality rate was 31.7% with survival rate at 90 days of 68.3% (95% CI: 62.6 to 73.2). Poor prognostic factors identified in the multivariable cox regression included age ≥ 50 (HR 1.66; 95 CI 1.05 - 2.64; p = 0.029), ECOG 2-4 (HR 2.34; 95 CI 1.51 - 3.63; p < 0.001), vaccine naive (HR 3.06; 95 CI 1.85 - 5.06; p < 0.001) and absolute lymphocyte count (ALC) < 0.5 (HR 1.51; 95 CI 0.96 -2.38; p = 0.080). Age ≥ 50 (OR 2.43; 95 CI 1.41- 4.24; P = 0.001), ECOG 2-4 (OR 2.72; 95 CI 1.51 - 4.99; p <0.001), refractory hematological disease (OR 2.15; 95 CI 1.19 - 3.91; p = 0.011) and usage of B cell depleting monoclonal antibody (OR 8.25; 2.80 - 30.74; p <0.001) were significantly associated with severe Covid-19 infection. Conclusion: 45% of hematological patients with COVID-19 had severe or critical infection with mortality rate of 31.7%. Poor survival was correlated with older age (≥ 50 years old), poor performance status, severe lymphopenia and vaccine naive. Vaccination is effective in preventing mortality but not severe infection. Hence, antiviral drugs and anti-SARS COV-2 monoclonal antibodies for early treatment and prophylaxis should also be considered for high risk patients and potential vaccine non-responders. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Training Hematology and Medical Oncology Fellows in Performing Bone Marrow Biopsies- a Quality Improvement Initiative

Background Bone marrow biopsies are frequently performed in the evaluation of many benign and malignant hematologic disorders and occasionally utilized in the diagnostic evaluation of fever of unknown origin. 1 2 Guidelines for bone marrow biopsy samples vary. A size of 20mm for lymphoma , 15 mm for myeloproliferative disease , 16 mm for malignant neoplasms in general is considered to be a rough guide3. Bone marrow samples can be altered during the processing which may lead to shrinkage of up to 25% from the size obtained 5. Awareness and strict adherence to recommended bone marrow biopsy sample sizes seems limited. Type of bone marrow biopsy needle such as manual or motorized needles, operator skill and patient body habitus lead to variability in size, hemodilute aspirates and crush artifacts5. Suboptimal samples due to inadequate size or aspiration artifact can lead to delays in diagnosis, need for repeat procedures with physical, emotional and financial consequences4 . In our institution, we undertook a quality improvement initiative to improve upon the sample sizes and minimize artifacts of bone marrow biopsies and herein we report the results of this project. Methods: We collected data from the outpatient bone marrow biopsy clinic on all the bone marrow biopsies done by a class of hematology and oncology fellows between the months of July 2021 and January 2022 . Data was collected for 70 bone marrow biopsy encounters. Each encounter was analyzed for size , type of artifact if present, patient diagnosis, age, gender, BMI, number of attempts and use of sedation to assess meaningful correlations and potential contributing factors. We then performed individual one on one intervention sessions with each fellow participating in the project to review their individual operator data and discuss areas of improvement. A best practices handout with the steps to a successful biopsy and common pitfalls with useful tips was given to all the fellows and was placed in the bone marrow biopsy clinic for reference. A post procedure checklist was added and included a measuring aid to ensure that the bone samples were of the desired size which allowed practitioners to be more aware of the quality of their collected samples and intervene again if needed to get better samples in the same encounter. A survey was also utilized to understand the personal experiences and knowledge barriers that may be contributing to inferior outcomes and allow for anonymous feedback. Data was then collected again over a 6-month period post intervention to screen for improvement in percentage of adequate biopsies, average size of sample obtained and presence of artifacts. Results: Data obtained pre-intervention showed a 39.4% inadequate samples. The average bone marrow biopsy size was 1.2 cm, 95% CI ( 1.05- 1.35). There was a 22.5% aspiration artifact in the tested samples along with 16.9% and 1.4% fragmentation and crush artifacts respectively. Interestingly the size of adequate samples in this pre-intervention cohort of biopsies was 1.23cm 95% CI (1.04-1.42) , indicating that the percentage of inadequate samples was mostly influenced by high degree of artifacts in the obtained samples. In addition, patient age, BMI and diagnosis did not correlate with percentage of inadequate samples suggesting operator skill and technique as the main factor in determining outcomes. Of the 49 post intervention samples analyzed, the average size of the sample was 1.2cm, 95% CI ( 1.03- 1.37) which was similar to the pre intervention samples . but there was a difference in the size of the adequate samples at 1.43cm 95% CI ( 1.27-1.59) , . 8.1% of samples had aspiration artifact . 8.1%of samples had fragmentation. Overall, this intervention resulted in a decrease in the inadequate sample rate from 39.4% to 26.5% Conclusion: Bone marrow biopsies are an important part of investigating a wide array of diseases , personal skill and experience are important factors in determining adequacy of samples , there is merit behind a combined approach of individualized feedback along with tools such as post-procedure checklists for self-evaluation to improve the quality of collected bone marrow biopsy samples in new Hematology and Oncology fellowship trainees. Novel approaches such as utilization of image guidance or ultrasound may be worth exploring to further improve sampling yield.

Acute myeloid leukaemia following direct acting antiviral drugs in HCV-infected patients: A 10 years’ retrospective single-center study

BackgroundAfter several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not. Material/methodsIn this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM. ResultsOver the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodgkin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA–, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelodysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No significant difference between the groups DAA + and – was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively). ConclusionAML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results.

Pain and anxiety associated with bone marrow aspiration and biopsy

Introduction: Bone marrow biopsy (BMB) and aspiration is a fundamental part of the diagnostic workup of various benign and malignant hematological disorders. Improved via several variations and technical modifications ever since its advent in the early nineteenth century, the procedure plays a central role in establishing diagnosis in various hematological and systemic diseases.Materials and Methods: This is a prospective study conducted in the Department of Pathology, Tertiary Care Teaching Hospital over a period of 1 year. Sixty-four patients met the criteria of the study (adults aged ≥18, not having communication barrier or any kind of mental illness) and agreed to take part in the study. To gather the research data, personal information form. It is used to determine the risk group by identifying anxiety and depression, not with the aim of making a diagnosis for the patients who consult to primary care health service and have physical diseases. Anxiety before and pain during the procedure were assessed by patient interview 10 minute before and 10 minute after the procedure, respectively. A numerical rating system (NRS) scale, ranging from 0 (no symptom) to 10 (the worst), was administered to score symptom intensity.

Single Centre Experience: Bening and Malign Hematological Patients with COVID-19

Introduction &#x0D; Coronavirus disease 2019 (COVID-19) were declared as pandemic by World Health Organization. With this study, we aimed to define our patients who were followed up with malign or benign hematological diagnoses and diagnosed with COVID-19; determine the distribution of this infection in patient groups and contribute to the literature by creating descriptive statistics with its clinical and demographic features.&#x0D; Patients and methods: &#x0D; It is planned to retrospectively examine patients with a history of COVID-19 who were followed up in Hematology Department of Dışkapı Yıldırım Beyazıt Training and Research Hospital with benign and malignant diagnoses.&#x0D; Results: &#x0D; 88 patients who had COVID-19 infection while being followed in our clinic due to hematological diseases were included in the study. 77 patients had been followed by hematologic malignancies and 11 patients had been followed by benign hematological disease.In the group with malignancy, COVID was found most frequently in patients diagnosed with Philadelphia chromosome negative myeloproliferative neoplasms (22%), nonhodgkin lymphoma (19%) and multiple myeloma (16%). ITP (64%) was the most common disease in patients with benign hematological disorder who had COVID history. 52 (67%) of the malignant cases and 8 (73%) of the bening cases were found to be followed up with the disease in remission.&#x0D; The all patient's most common symptoms at COVID-19 diagnosis were fever (77%), cough (70%) and weakness (65%). 45% of the patients were isolated at home, 48% were required hospitalization. 49% of patients had mild; 27% had moderate and 24% had severe COVID-19 infection. Almost all of the patients in the moderate and severe disease group were followed up in patients diagnosed with malignant hematological disease. 16 (18%) patients received mechanical ventilation and 16 (18%) patients was transferred intensive care unit. All of the patients who were intubated and needed intensive care were diagnosed with malignant hematological disease. 17 patients died due to COVID-19 infection. The mortality rate was 22% in patients with diagnosis of malignant hematological diseases, and 19% when all patients (malignant and bening) were included. &#x0D; Conclusion: &#x0D; In conclusion, the COVID-19 pandemic is a problem all over the world. Determining the course of the disease in certain diagnostic groups is important in the management of both the main disease and the COVID-19 infection. Therefore, the contribution of such recording studies to the literature is important and valuable.

Effect of CD34+ cell dose on neutrophil and platelet engraftment kinetics in haematopoietic stem cell transplantation – A single-centre experience

Objectives: Haematopoietic stem cell transplantation (SCT) is curative for a number of benign and malignant hematological disorders. CD34 expression on haematopoietic progenitor cells is used to assess stem cell content in peripheral blood stem cell and bone marrow grafts. This study evaluated the relationship between numbers of CD34+ cells infused per kg and the timing of neutrophil and platelet engraftment. Materials and Methods: The effect of cell dose was studied in consecutive HSCT patients transplanted between November 2008 and December 2017. Neutrophil engraftment was defined as the first of 2 consecutive days with an absolute neutrophil count &gt;0.5 × 109/L and platelet engraftment as unsupported platelet count &gt;20 × 109/L for 7 days. Results: Of a total of 131 patients, 26 (19.8%) underwent an autologous SCT, while 105 (80.2%) underwent an allogeneic SCT. The median CD34 dose infused in the auto-SCT group was 5.29 × 106 CD34+cells/kg (IQR = 2.95–10.98) and 6.42 × 106 CD34+cells/kg (IQR = 4.20–9.20) in the allo-SCT group (P = 0.773). The median time to neutrophil engraftment in the auto-SCT group was 11 days (range 9.5–12) and in the allo-SCT group was 15 days (range 13–17), P ≤ 0.001. The median time to platelet engraftment in both groups was similar (12 days). When patients were divided into three groups based on CD34 dose (&lt;5, 5–8 and &gt;8), no difference was observed in the time to ANC or platelet engraftment. Similarly, no differences in time to engraftment were noted in each quartile of CD34 dosage in auto- and allo-SCT. Conclusion: Thus, it was concluded that a cell dose of approximately 5 × 106/kg provides reasonably rapid engraftment, with no advantage seen for a higher cell dose of &gt;5.

Chronic Opioid Use Is Highly Prevalent in Patients Undergoing Allogeneic Transplant and Impacts Long Term Outcomes

Opioid analgesics are used to treat cancer-related pain and improve quality of life, however overuse of these high-risk drugs has been associated with significant public health implications as exhibited by the national attention received during the opioid pandemic. In addition, pain associated with hematologic malignancies is frequent yet not well understood. There is no data examining opioid use and outcomes in patients with hematologic malignancies and recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we sought to describe chronic opioid use (COU) and its impact on long-term outcomes in patients undergoing allo-HSCT.We analyzed outcomes of adult patients ≥ 18 years (n=159) diagnosed with hematologic malignancies (n=151) or benign hematologic disorders (n=8) (excluding sickle cell disease) who received allo-HSCT between 2012 and 2019 at a single urban medical center. COU was defined as having a documented active prescription for 3 consecutive months. Daily opioid doses were converted to morphine milligram milliequivalents (MME) using standard conversion factors.Among the entire cohort, the median age was 55.4 (19.4-74.3) years, 94 (59.1%) were male, 70 (44%) were White, 42 (26.4%) were Hispanic, and 26 (16.4%) were Black. The majority of patients were diagnosed with acute leukemia, with 89 (56%) having AML and 16 (10%) having ALL patients. Of the remaining patients, 14 (8.8%) were CML-BP or CML-AP, 16 (10%) NHL/HD, and 15 (9.4%) MPDs. 33.5% of patients were found to have high or very high DRI prior to allo-HSCT. Most patients received either a myeloablative (n=102, 64.2%) or reduced-intensity (n=55, 34.6%) conditioning regimen.At baseline (immediately prior to allo-SCT), COU was observed in 38 (23.9%) patients, 20 (52.6%) of which were diagnosed with AML. Only 23 (60.5%) patients with COU had a documented indication for opioid analgesia. The baseline median MME per day was 23.5mg (range: 2-150). In logistic regression analysis including demographic and social factors such as insurance type (i.e. Medicare, Medicaid, private payer), education level, smoking, alcohol, illicit drug and/or benzodiazepine use, and employment status, only older age (RR 0.97, 95% CI 0.94-0.99; p=0.026) was associated with a lower likelihood of baseline COU.In total, 149 (93.7%) patients received opioids during the allo-HSCT admission, while 45 (28.3%) were discharged on opioids. The reason for being discharged on opioids was related to musculoskeletal pain (n=19), residual mucositis-related pain (n=7), and headache (n=3). This was found to persist over time, with 35 (92.1%) of the 45 patients discharged on opioids remaining on opioids at 180 days after allo-HSCT thus meeting the definition for COU. The only factor found to predict for COU at 6 months was discharge from initial transplant hospitalization with an opioid (RR 2.24, 95% CI 1.16-4.32, p=0.016). Not only did a significant number of post-transplant survivors meet the definition for COU, but the MME was found to be relatively high with a median of 50mg (range: 10-540) at discharge and 30mg (range: 4.5-202) on days +30, 90, 180 as well as at 1 and 5 years after allo-HSCT.In a multivariable modified Poisson regression with robust standard errors for binary outcomes, when adjusted for established prognostic characteristics (i.e., disease, DRI, HCT-CI), we found that COU prior to admission strongly predicted for worse overall survival (HR 2.99, 95% CI 1.59-5.64; p=0.001), progression free survival (HR 2.72, 95% CI 1.48-4.99), and GVHD free, relapse-free survival (HR 1.78, 95% CI 1.05-3.03; p=0.033).This study is the first to describe patterns of COU, an important public health problem, among patients undergoing allo-HSCT, and in particular in long term survivors. We demonstrate high rates of baseline COU in patients undergoing allo-HSCT as well as persistent long term COU, which is linked to prescribing patterns after the initial transplant hospitalization. In addition, we show the negative impact of baseline COU on overall survival, even when adjusted for disease- and transplant-related factors. These data highlight the need to improve understanding and management of pain in hematologic malignancies as well as to reinforce the need for continuous reassessment of the use of opioids prior to and after allo-HSCT. DisclosuresCalip: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company; Pfizer: Research Funding. Rondelli: Vertex: Membership on an entity's Board of Directors or advisory committees. Patel: Celgene: Consultancy.