Diagnosis Of Hematological Malignancies Research Articles

How Caregivers Cope and Adapt When a Family Member Is Diagnosed With a Hematologic Malignancy: Informing Supportive Care Needs.

Informal family caregivers (FCs) of adults with various diseases including hematologic malignancy (HM) experience low quality of life and psychological well-being. Although HMs are life-threatening cancers associated with high mortality, numerous symptoms, and lengthy hospitalizations and are therefore likely to be challenging for FCs to cope with, there is scant research exploring FC experiences. The aim of this study was to describe the coping and adaptation of FCs of patients during diagnosis and treatment of HM. This study used a qualitative descriptive design to analyze semi-structured interview responses from FCs (N = 28) within 3 months of the patients' HM diagnosis. A content analysis was conducted to generate common themes. Family caregivers endorsed adaptive and maladaptive coping. Adaptive strategies included taking one day at a time, spirituality, engaging in pastimes, and utilizing emotional and instrumental family and community support. Maladaptive coping included wishful thinking, harmful habits, avoidance, and lacking or being unable to accept family and community support. Findings highlight the complexities of caregiver burden as they support their loved ones with HM. Family caregivers would benefit from receiving an interdisciplinary family-centered approach as their HM person is initiating treatment. Nurses should consider assessing the FCs' psychosocial needs to help facilitate appropriate services, such as palliative care consultations, social work referrals, support groups, and/or counseling.

Noble metal nanomaterials for the diagnosis and treatment of hematological malignancies.

Recently, the incidence of hematological malignancy, such as various leukemias, multiple myeloma and lymphoma, has revealed an increasing tendency, exhibiting a major impact on human health. Most of the available anti-cancer drugs, however, possess high non-targeted accumulation, dosage-associated toxicity, fast elimination, and lack specificity towards tumors, which restrict their utilization in clinical therapy. This extends also to cancer diagnosis where there is a lack of predictive biomarkers. Noble metal nanomaterials (NM NMs) have the potential to overcome these shortcomings due to several characteristics including ease of synthesis, ultra-small size, easy surface modification and specific physicochemical properties. At present, gold-, silver- and platinum-based nanomaterials have been employed in the tracing and treatment of hematopoietic tumors through direct individual endocytosis or in innovative drug delivery systems (DDS) by conjugation with other targeting biomolecules. In this mini review, we focus on the use of localized surface plasmon resonance (LSPR)-/surface-enhanced Raman scattering (SERS)- and fluorescence-based diagnosis of NM NMs in the hematological malignancies. Furthermore, the treatment of hematological malignancies utilized the NM NMs or NM NMs-based therapy technology in the chemotherapy, targeted therapy, and photothermal therapy are depicted in depth. The construction of effective and promising NM NMs or NM NMs- dependent theranostic methodology has the potential to provide interdisciplinary knowledge in the development of clinical tracing, diagnosis and treatment of refractory hematological diseases.

Diagnostic importance of bone marrow aspiration evaluation: A single-center study.

Background & Objective:Early diagnosis can be made based on the morphological examination of bone marrow aspiration (BMA) until the bone marrow biopsy (BMB) result is reported. This allows for treatment to be started immediately, especially in hematological malignancies for which urgent treatment is indicated. This study aimed to determine the sensitivity and importance of bone marrow aspiration in the diagnosis of hematological malignancies.Methods:In this study, the data of patients who underwent bone marrow aspiration and bone marrow biopsy in Van Yuzuncu Yil University hospital between 2017 and 2019 were retrospectively analyzed. A total of 500 patients who simultaneously underwent BMA and BMB were included in the study. Data were obtained from electronic medical records.Results:Indication for bone marrow evaluation was abnormalities in complete blood count in 270 (54%) of patients. The diagnosis was made based on the evaluation of BMA in 475 (95%). In 456 (96%) of the 475 patients diagnosed with BMA, the diagnosis was consistent with that of BMB. Agreement of BMB with BMA was 100% in acute and chronic leukemias, while BMA was not sufficient for the diagnosis of lymphoma and solid organ metastasis.Conclusion:Our study showed that the evaluation of BMA was highly sensitive in the diagnosis of hematological malignancies, such as acute leukemias, chronic leukemias, and multiple myeloma.

11. Optical genome mapping for chromosomal structural variants analysis in hematological malignancies

Knowledge of copy number (CNVs) and structural variants (SVs) is important for the diagnosis and management of hematological malignancies (HM). In myelodysplastic syndromes (MDS), the number and type of SVs/CNVs are essential for prognostic risk-stratification using R-IPSS. Optical genome mapping (OGM) is a novel, single-platform, cytogenomic technique for genome-wide characterization of all types of CNVs/SVs at a high resolution. In this study, we evaluated the performance of OGM in a series of previously well-characterized 49 hematological malignancies (46 MDS, 1 AML and 2 T-ALL) compared to standard-of-care cytogenetic tests.

Applications of electrochemical biosensors based on 2D materials and their hybrid composites in hematological malignancies diagnosis.

Hematological malignancies encompass a wide variety of severe diseases that pose a serious threat to human health. Given the fact that hematological malignancies are difficult to treat due to their unpredictable and rapid deterioration and high rates of recurrence, growing attention has been paid to their early screening and diagnosis. However, developing a rapid and effective diagnostic tool featuring a noninvasive sampling technique is still extremely challenging. In recent years, novel nanomaterials-based electrochemical biosensors have attracted great interest because of such advantages as simple operation, low cost, fast response, etc. As a kind of rising nanomaterials, two-dimensional materials have excellent electronic and chemical properties, which have been proven to improve the performance of electrochemical biosensors. This review summarizes the applications of different types of electrochemical biosensors (nucleic acid sensors, immunosensors, aptamer biosensors, and cytosensors) based on two-dimensional materials in the detection of biological molecules related to hematological malignancies. Two-dimensional materials-based electrochemical biosensors designed for the diagnosis of leukemia could rapidly detect the target biomolecules at a trace level and show great merits such as wide linear range, low detection limit, high sensitivity, excellent selectivity, and cost-effectiveness. In addition, these biosensors have also achieved satisfactory results in the diagnosis of lymphoma and multiple myeloma. Thus, two-dimensional materials-based electrochemical biosensors are attractive for the early diagnosis of hematological malignancies in clinical practice. Nevertheless, more efforts are still required to further improve the performance of electrochemical biosensors. In this review, we propose the possible main concerns in the design of future two-dimensional materials-based electrochemical biosensors, involving the development of sensors for synchronous detection of diverse target biomolecules, the exploration of other superior two-dimensional materials, the simplification of the sensors fabrication process, the construction of new hybrid structures and how to avoid possible environmental issues.

Patterns of haematological malignancies on bone marrow examination: A 3-year institutional experience

Aims and Objectives: Haematological malignancy may show varied presentation in different regions of world, however, Uttarakhand lacks any recent data about them. The present study was therefore conducted to study the pattern of haematological malignancies on bone marrow examination in institute of Uttarakhand. Materials and Methods: This study was conducted at All India Institute of Medical Sciences, Rishikesh, Uttarakhand, over a period of 3 years. It included patients of haematological malignancies diagnosed on bone marrow examination. Patient's age, sex, clinical history and bone marrow diagnosis were noted for every case. All the data were entered into the excel sheet and statistically analysed. Results: The study included total 256 cases of haematological malignancies with male:female ratio of 1.13:1 and mean age of 39.3 years. Chronic myeloproliferative neoplasm (CMPN) was the most common haematological malignancy (49%) with chronic myeloid leukaemia (CML) being its most common type (40%). All the haematological malignancies showed male preponderance except for non-Hodgkin's lymphoma. Mean age of CMPN was 45.81 years and of acute myeloid leukaemia was 36.92 years. Bone marrow aspirate (BMA) and trephine biopsy (BMT) together were able to diagnose 81.3% of cases of haematological malignancies. Conclusion: The study concludes that haematological malignancies present at lesser age with male preponderance in Uttarakhand. CML is the most common haematological malignancy followed by acute lymphoblastic leukaemia. BMA and BMT are complimentary to each other for diagnosis of haematological malignancies and should be used together to avoid missing of any case.

Application of Dynamic Enhanced Magnetic Resonance Imaging in the Diagnosis of Hematological Malignancies.

The use of dynamic enhanced magnetic resonance imaging technology can effectively explore the diagnosis and clinical application of hematological malignancies. This paper selected 60 patients with hematological malignancies from 2015 to 2019; all of whom were diagnosed with hematological malignancies, including 40 men and 20 women, aged between 40 and 77 years. The main clinical manifestations of the patient are hematological malignancies, fever, and other symptoms. We used Siemens 3.0T to perform MRI and dynamic enhanced MRI examinations on 30 patients with hematological tumors. The PACS system was used to collect and organize clinical data. All patients were pathologically confirmed and clinically diagnosed with hematological malignancies. Based on the clinical data of the patients, retrospective analysis and summary were conducted and the clinical manifestations of hematological malignancies were discussed. The results showed that the diagnostic accuracy of 30 cases of dynamic enhanced MRI was 100%, while the diagnostic accuracy of ordinary MRI was lower than that of dynamic enhanced MRI, P < 0.05, and the difference was statistically significant. In addition, compared with dynamic enhanced MRI and MRI, P > 0.05, the difference was not statistically significant. Therefore, the application of dynamic enhanced MRI in the diagnosis of hematological malignancies is valuable.

985. Fusarium Infections in Patients with Hematological Malignancies

Abstract Background Fusarium is a ubiquitous mold that can cause invasive and disseminated fusariosis in immunosuppressed patients, especially those with hematological malignancies. The risk factors associated with mortality of patients with Fusarium infections have not been adequately assessed in literature. In this study, we sought to explore the characteristics, clinical outcomes, and risk factors for mortality in Fusarium infections in patients with hematological malignancies. Methods This is a retrospective study of adult hematological malignancy patients admitted to surgical/medical wards or critical units at an academic medical center from January 2010 to January 2021 and diagnosed with proven invasive Fusarium infections through positive microbiological culture data from a biopsy, surgical specimen or sterile site. Primary end point was 30-day mortality. Statistical analysis was done using Fischer’s exact test and Mann-Whitney U test. Results 31 patients with hematological malignancies were identified with proven Fusarium infections during the 10-year period (13,390 total unique patients with diagnosis of hematologic malignancies). Two were excluded due to incomplete data. Demographic characteristics, type and status of hematological malignancy, chemotherapy, exposure to steroids, neutropenia, lymphopenia, antifungal prophylaxis, and other factors were analyzed. Mean age at diagnosis was 52.6 years. 16/29 (55.2%) had undergone stem cell transplant prior to infection with median duration of 150.5 days (range 12 to 1503) prior to infection. The most common pathologies were invasive sinusitis and disseminated cutaneous infection in 13/29 (44.8%) patients. Blood culture was positive in 5/29 (17.2%). Overall mortality was 86.2% with 30-day mortality of 44.8% and 1-year mortality of 83%. Death was attributed to fusariosis in 12/25 (48%). Median duration to death was 56 days (range 2 to 1627 days). Risk factors for 30-day mortality were assessed (table 1). The table describes risk factors for 30-day mortaity for fusarium infections in patients with hematological malignancies. statistical analysis done using fischer’s exact test Conclusion Fusarium infections result in morbidity and mortality in patients with hematological malignancies. A variety of host and disease factors dictate eventual outcome of Fusarium infections in these patients. Lack of neutrophil recovery is a significant risk factor for 30-day mortality in this population. Disclosures All Authors: No reported disclosures

Improvement of Standardization of Molecular Analyses in Hematology: The 10-year GBMHM French Experience.

Molecular tests have become an indispensable tool for the diagnosis and prognosis of hematological malignancies and are subject to accreditation according to the International Standard ISO 15189. National standardization of these techniques is essential to ensure that patients throughout France benefit from the same care. We report here on the experience of the GBMHM (Groupe des Biologistes Moléculaires des Hémopathies Malignes). By organizing External Evaluation of Quality (EEQ) programs and training meetings, the GBMHM has contributed to improvement and standardization of molecular tests in 64 French laboratories. A retrospective analysis of the quality-control results of 11 national campaigns spanning 10 years was performed for the 3 most frequently prescribed tests: BCR-ABL1, JAK2 V617F, and lymphoid clonality. For each test, particular attention was placed on comparing methodologies and their evolution throughout the period. The establishment of the BCR-ABL1, JAK2 V617F, and lymphoid clonality EEQ programs and the associated training meetings have initiated a process of collective standardization concerning the methods of implementation (JAK2 V617F) and the interpretation and formulation of results (lymphoid clonality). In addition, it resulted in objective improvement in technical performance (BCR-ABL1). Our evaluation of the impact of these EEQ programs demonstrates that it is possible to obtain reproducible values across different laboratories in France by applying national recommendations. To our knowledge, this is the first publication that evaluates the impact of a national quality assurance program on improving molecular results in hematology.

Abstract 11514: Extracorporeal Membrane Oxygenation is a Feasible Life Saving Modality for Adult Patients With Neoplasms- Outcomes and Trends in the Last Two Decades

Introduction: Extracorporeal Membrane Oxygenation (ECMO) is utilized in the management of severe respiratory and circulatory failure. Advanced malignancy is a relative contraindication but the indication for ECMO in the oncologic population has not been clearly established due to the wide spectrum of malignant disease and prognoses. Hypothesis: ECMO is a feasible treatment modality in selected adult oncologic population. Method: The Extracorporeal Life Support Organization (ELSO) database was queried for patients older than 18 years with an International Classification of Diseases (ICD) code of neoplasm over the past two decades (2000-2019). The data were divided into two decades to analyze and compare the trends with background and outcomes. Results: One thousand, six hundred, and ninety-seven patients met inclusion criteria from the last decade which is more than 15 times the number from the previous decade (n=110). Compared with the previous decade, ECMO was used more in patients with older age (56 vs 50.5 years old; p&lt;0.001), cardiac and extracorporeal cardiopulmonary resuscitation (ECPR) support type (p = 0.001), higher P/F ratio (79.0 vs 61.8; p=0.001), and lower oxygenation index (23.0 vs 35.6; p&lt; 0.001) in the last decade. Although survival did not show significant improvement overall (38.9% [660 of 1697] vs 33.6% [37 of 110]; p=0.272), survival in pulmonary ECMO has significantly improved in the last decade (41.6% [409 of 983] vs 29.1% [23 of 79]; p=0.030). Diagnosis of hematologic malignancy, ECPR, and hematopoietic stem cell transplant were identified as predictors of poor prognosis (p = 0.025, &lt;0.001, and 0.021 respectively). Conclusion: Utilization of ECMO for patients with neoplasms has increased over time mirroring the overall increase of adult ECMO. With careful patient selection, ECMO can be successful in oncologic population.

Characteristics and Outcomes of Adult Patients with Malignancy-Associated Hemophagocytic Lymphohistiocytosis: A Single-Center, Prospective Analysis

Characteristics and Outcomes of Adult Patients with Malignancy-Associated Hemophagocytic Lymphohistiocytosis: A Single-Center, Prospective Analysis

Primary Care Physician-Based Telemedicine in Non-Malignant Hematology: Prospective Analysis of 790 Consecutive Cases

Introduction: In-person hematology appointments (IHA) are not available in most hospitals and outpatient centers in the state of Santa Catarina, Brazil. Primary care physician (PCP) based hematology telemedicine consultation (HTC) has the potential of being a valuable and cost-effective tool for patients and PCPs. While it has not been previously assessed in our country, it may avoid unnecessary IHA, which frequently require traveling to major cities, reduce waiting times for an IHA, and advise PCPs on better assessing patients that may need a hematology referral.Methods: Sistema Integrado Catarinense de Telemedicina is a statewide online tool to which all public health system PCPs have access. It enables PCPs to set up asynchronous HTCs that are randomly distributed to reference hematology treatment centers. HEMOSC Joinville is one such center and is responsible for approximately one fifth of all HTCs. We prospectively assessed all HTC requests in non-malignant hematology between August 2019 and July 2021 for main clinical features that prompted a hematology referral. All cases with confirmed or likely diagnosis of hematological malignancy under the 2017 World Health Organization (WHO) classification were excluded. WHO anemia definition and severity classification was observed. Severe neutropenia and thrombocytopenia required counts below 500 and 50,000 per microliter. For every HTC, a single diagnostic hypothesis in hematology (DHH) was established based on patient data provided by the PCP.Results: Seven hundred and ninety consecutive patients aged 15 or older were included. Median age at HTC was 55 years (interquartile range, IQR: 39-70), with 282 patients (36%) aged 60 or more. Sixty percent of patients (n=472) were women, with 26 pregnant women (3%) at a median gestational age of 15 weeks (IQR: 12-21). Major DHHs were iron deficiency anemia (n=123, 16%), anemia of undetermined cause (n=107, 14%) and unexplained thrombocytopenia (n=102, 13%). Cytopenias accounted for 499 (63%) of all DHHs. Abnormal complete blood count (CBC) or coagulation tests were the sole reason for HTC, in the absence of any attributable clinical finding, in 597 cases (76%). DHHs were adequately formulated by PCP in 140 cases (18%). CBC information was provided in 594 cases (75%), with mild anemia (n=188, 32%) being the most frequent finding. Median hemoglobin when anemia was the DHH was 10 g/dL (IQR: 8.7 - 11.1). Absence of red blood cell (RBC) indices, differential leukocyte counts and platelet counts were seen in 261 (44%), 441 (74%) and 251 (42%) cases. CBC was collected in excess of 60 days prior to HTC in 118 patients (20%) and no CBC information was provided for 196 patients (25%), 31% of which (n=60) had a cytopenia as DHH. Blood transfusions were reported within 60 days of HTC in 49 patients (6%), and an emergency department evaluation was suggested by the hematology specialist for 72 patients (9%). One hundred and ninety (24%) patients were referred to an IHA after HTC, of which 21 (3%), 115 (15%) and 54 (7%) received low, intermediate and high priority for an appointment.Conclusions: Over the reported two-year period, HTC has prevented 3 in every 4 IHA in our patient population. This is especially relevant considering the need for social distancing and the socioeconomic impacts of the COVID-19 pandemic. Follow-up analyses of these patients to identify IHA at a later date and the confirmation of hematological diagnosis are in order. This study also uncovers inappropriate CBC interpretation and reporting, and failure to associate clinical symptoms and patient history to laboratory findings, which in turn demands providing PCPs with continued medical education in hematology. [Display omitted] DisclosuresBoettcher: Novartis: Speakers Bureau.

Cardiovascular Side Effects of Chimeric Antigen Receptor (CAR) T-Cell Products: A Single Center Experience in a Minority Rich, Ethnically Diverse Real-World Cohort

Introduction:Axicabtagene ciloleucel (Axi-Cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated efficacy in patients with refractory large B cell lymphoma when conventional treatments failed. Cardiovascular side effects of CAR-T therapy that have been noticed so far include hypotension, left ventricular dysfunction, heart failure and cardiogenic shock in settings of CRS. We aimed to assess the cardiovascular side effects in a racially/ ethnically diverse patient population who underwent CAR-T cell therapy.Methods:This study included thirty-four consecutive adult patients who underwent treatment with CAR-T cell product Axi-Cel at an academic health system between 2018-2021. We performed detailed chart reviews and collected information related to the age, gender, hematological malignancy diagnosis, other medical comorbidities, therapeutic regimens, pretreatment cardiac risk factors, development of CRS with grading , pre and post treatment electrocardiograms ( EKG), transthoracic echocardiograms( TTE) , death, cause of death, and duration between administration of CAR-T products and death of the patients . We collected data pertaining to development of hypotension, EKG changes, arrhythmias, left ventricular systolic dysfunction, heart failure (HF), acute cardiac syndrome (ACS), troponin elevation, echocardiographic changes post CAR-T cell therapy, and follow up visits after 60 days to get information pertaining to development of hypotension, tachycardia or SOB, need for further cardiac work up, and cardiology referral.Results:Mean age of our study participants was 65 years ranging between ages of 30 and 84 years with 38 % (13/34) female and 62% (21/34) male study participants. Study population was predominantly Hispanic, white and African American with percentages of 35% (12/34), 32% (11/34), 26 %(9/34) respectively followed by categories Asian 2.9% (1/34) and other at 2.9 %( 1/34). Sixty seven percent (22/37) patients had primary diffuse large B cell lymphoma (DLBCL) and 32% (11/34) had different primary malignancy with transformation into DLBCL. Thirty eight percent individuals had received autologous stem cell transplant. Sixty one percent (21/34) of our study participants developed cytokine release syndrome, with CRS grades 1-3 in 57% (12/29), 25% (08/21) and 4.7% (1/21) respectively. Thirty four percent (09/34) study participants died after cellular therapy. Septic shock and disease progression each were primary cause of death in 55 % (5/9) of patients, followed by respiratory failure in 22% (2/9) and ventricular fibrillation leading to cardiac arrest in 11% (1/9) of the patients. Mean duration of time between administration of therapy and death was 70 days. The cardiovascular effects noted immediately post CAR-T treatment and observations from follow up oncology visits are listed in Table 1. Troponin elevation was noticed in two study participants in settings of CRS, but one participant exhibited troponin elevation in absence of CRS. Seventeen percent of patients (6/34) developed left ventricular dysfunction after Axi-Cel. Most of them had concurrent CRS but one case of fatal heart failure occurred in absence of CRS. Three patients developed fatal arrhythmias post CAR-T therapy (1- Non sustained ventricular tachycardia in settings of CRS, 2- supraventricular tachycardia in settings of CRS, and 3- ventricular tachycardia needing defibrillation without CRS). Only one patient developed ACS in settings of CRS which lead to patient's demise.Conclusions: In a real world, minority rich cohort, we observed that a significant number of our patients had preexisting cardiovascular findings including abnormal EKG (30% excluding sinus tachycardia) or abnormal echocardiographic findings (46%). Hypotension (68%) and sinus tachycardia (59%) were the most commonly observed cardiovascular toxicities. Although Axi-Cel was in general safe and well tolerated, we observed cardiovascular side effects associated with and independent of CRS. Notably, six patients (17%) developed left ventricular dysfunction including one fatality which was independent of CRS. There was only one fatal coronary syndrome and two cases of troponin elevation in our series. Our study stresses the importance of a thorough cardio-oncology evaluation before proceeding with cellular therapies as well as involved follow up during and after hospitalization. [Display omitted] DisclosuresGritsman: iOnctura: Research Funding. Shastri: Kymera Therapeutics: Research Funding; Onclive: Honoraria; Guidepoint: Consultancy; GLC: Consultancy. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company.

Anti-Spike (S) Antibody Production Post Covid-19 Vaccination after B Cell Depleting Therapy (BCDT) for Non-Hodgkin Lymphoma (NHL)

Introduction:Patients with NHL have a longer duration of illness and higher mortality rate after infection with Covid-19 1-3. Vaccination is strongly recommended to mitigate these problems in the general population, however, patients with cancer were not eligible to enter the pivotal vaccine trials. Furthermore, patients with NHL as well as other hematologic malignancies are frequently treated with B cell depleting therapies (BCDT) such as Rituximab and other anti-CD20 antibodies which in theory affect antibody production after vaccination. There are no data in the literature regarding patients with NHL and scarce data on other tumors concerning the antibody response against the S protein of Sars-Cov-2. To investigate the production of antibodies against the spike protein following vaccination against Sars-Cov-2, we studied 180 patients with cancer. We also aimed to determine if factors such as timing of BCDT in relation to number of days elapsed between such treatment and vaccination, as well as other features such as peripheral blood absolute B cell count correlate with antibody production.Materials and Methods:Anti-spike protein antibody production was evaluated in 104 patients with NHL and 76 with other malignancies. Eligible participants were aged 21 years or older. Study inclusion criteria included diagnosis of lymphoma or other hematological malignancy as well as solid tumors.The Dimension Exel 200 method for qualitative detection of total antibodies was used to determine antibody production. The antibody test was performed > 14 days after the second Moderna or Pfizer vaccine dose or after the Johnson & Johnson single dose.We prospectively evaluated antibody production following administration of BCDT as well as cytotoxic chemotherapy in 104 patients with NHL, 27 hematologic malignancies and in 49 solid tumors. In addition, we explored the timing of such treatments in relation to the vaccination date as well as the type of vaccine administered.Results:Median age was 61 and 59% were females. Of 180 entered, 104 had NHL. Of these, 95 (91.3%) were treated with BCDT, including rituximab (89), obinutuzumab (5) or anti-CD19 CAR-T cell therapy (1). BCDT was usually given together with induction chemotherapy and followed by maintenance. Histologic types of NHL treated with these therapies were: aggressive NHLs (N=35), follicular low grade (N=33), marginal zone NHL (14) and others (N=13). There were 49 patients with solid tumors. We also included 10 patients with other hematologic tumors who received BCDT and were analyzed together with the 95 NHLs to determine if this treatment interfered with anti-spike antibody production.Conclusions:These results imply a deleterious effect of BCDT on the humoral immune response to the SARS-Cov-2 vaccine. The correlation between the administration of BCDT and poor production of anti-spike antibodies is very robust, particularly in those cases who were vaccinated 9 months or less after BCDT. However, administration of cytotoxic chemotherapy without BCDT was not associated with reduced production of antibodies. In fact, almost all patients (94%) who received cytotoxic chemotherapy without BCDT, produced antibodies against spike protein (table 2). However, when chemotherapy was combined with BCDT there was a significant reduction of antibody production. These results strongly suggest that the major problem with poor antibody production following vaccination against Sars-Cov-2 relates to the use of BCDT and not so much to cytotoxic chemotherapy. The same findings apply to the 104 cases of NHL where half of patients treated with BCDT did not produce antibodies while 88% who did not receive BCDT produced antibodies (table 2). Almost all patients with solid tumors in our study (95.9%) were able to produce antibodies, irrespective of whether they received chemotherapy or not.These data raise the question whether vaccinated patients treated with BCDT who failed to make antibodies against the spike protein, could also benefit from a third dose. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risks for Hospitalization and Death Among Patients with Blood Disorders from the ASH RC COVID-19 Registry for Hematology

Risks for Hospitalization and Death Among Patients with Blood Disorders from the ASH RC COVID-19 Registry for Hematology

Thrombocytopenia Among Patients with Hematologic Malignancies and Solid Tumors: Risk and Prognosis

▪Introduction: Despite the large body of research in cancer and increasing numbers of cancer survivors, knowledge about the risks and prognoses related to thrombocytopenia in the clinical care setting is scarce. Such information is important to understanding the need and potential impact of platelet transfusion and emerging drug therapies for thrombocytopenia. In this study, we examined the risk of thrombocytopenia among patients with incident cancer. Further, we studied the extent to which thrombocytopenia was associated with adverse clinical outcomes.Methods: This population-based cohort study was conducted using data from the Danish Cancer Registry. All patients diagnosed with incident hematologic malignancies and solid tumors (age of ≥18 years) during 2015─2018 were identified. Data were linked with routine laboratory test results from the primary care and hospital settings, as recorded in the Danish Register of Laboratory Results for Research. Based on platelet count levels (x 10 9/L), thrombocytopenia was categorized as grade 0 (any count)<150; grade 1:<100; grade 2:<75; grade 3:<50; and grade 4: <25. We tabulated the prevalence of thrombocytopenia at study inclusion and calculated the cumulative incidence proportion (risk) of thrombocytopenia, accounting for the competing risk of death. Each patient with thrombocytopenia was matched up to 5 cancer patients without thrombocytopenia by age, sex, cancer type, cancer stage, and time from cancer diagnosis and index date. Cox proportional hazards regression analysis was used to compute hazard ratios (HRs) with 95% confidence intervals (CIs) of adverse clinical outcomes, including any bleeding leading to hospitalization, site-specific bleeding leading to hospitalization, transfusion (red blood cell, platelet, or fresh frozen plasma), and death. HRs were adjusted for Charlson Comorbidity Index scores and matching factors by design.Results: The analytic cohort comprised 11,785 patients with hematologic malignancies and 57,600 patients with solid tumors (median age=70 years). Any thrombocytopenia was observed during the 6 months preceding study inclusion among 18% of patients with hematologic malignancies (grades 1-2: 6% and grades 3-4: 5%) and 4% of patients with solid tumors (grades 1-2: 1% and grades 3-4: 0%). The 1-year and 4-year risks of new-onset thrombocytopenia were 30% and 40% for hematologic malignancies and 21% and 28% for solid tumors, respectively (Figure 1). Among patients who initiated chemotherapy following their cancer diagnosis (n=33,165), the 1-year and 4-year risks of thrombocytopenia were 50% and 62% for hematologic malignancies and 39% and 49% for solid tumors, respectively (Figure 2). Patients with grade 4 thrombocytopenia had higher rates of any bleeding leading to hospitalization than patients without thrombocytopenia [hematologic malignancies: HR=2.31 (95% CI: 1.43-3.73) and solid tumors: HR=4.52 (95% CI: 2.00-10.24)], while grades 1-3 thrombocytopenia did not confer a significantly increased rate of hospitalization for bleeding (Table 1). All grades of thrombocytopenia were associated with an increased rate of transfusion [overall for hematologic malignancies: HR=2.06 (95% CI: 1.91-2.23), and overall for solid tumors: HR=2.13 (95% CI: 1.83-2.48)] and with death [overall for hematologic malignancies: HR=2.01 (95% CI: 1.84-2.20), and overall for solid tumors: HR=1.44 (95% CI: 1.39-1.49)]. These associations increased in magnitude with decreasing platelet count levels.Conclusions: The risk of thrombocytopenia was substantial following a diagnosis of incident hematologic malignancy and solid tumors, with higher risks among patients who initiated chemotherapy. While only severe thrombocytopenia was a predictor of any hospitalization for bleeding, all grades of thrombocytopenia were associated with increased rates of transfusion and death. Our findings support the need for regular assessment of platelet count levels to identify cancer patients at risk of serious clinical outcomes. [Display omitted] DisclosuresClouser: Amgen: Current Employment, Other: This work is related to Chemotherapy Induced Thrombocytopenia as a disease state, in this essence it is not directly related to an Amgen product; CIT is an area of scientific interest to Amgen with Romiplostim under development for this potential indicati. Saad: Amgen: Current Employment, Current equity holder in publicly-traded company.

Four-Fold Increased Mortality from Sars-Cov-2 Infection in Patients with Hematologic Versus Non-Hematologic Malignancies Treated at the Largest Tertiary COVID-19 Center in Chicago/Rush University Medical Center (March 1, 2020-December 31,2020)

▪N.K.Y., P.C., & P.R.Y. contributed equally to this studyIntroduction: Many studies have concluded that active cancer patients infected with SARS-CoV-2 have a more complicated infection course and worse outcomes compared to the general patient population hospitalized with COVID-19. However, little evidence exists whether having a history of cancer plays a significant role in these observations. Patients with hematologic malignancy (HM) might have worse prognosis among all cancer patients but the reason remains unclear. Our objective is to evaluate outcomes and severity of COVID-19 in patients with Hematological Malignancy (HM) versus Solid-tumors (ST) in different clinical settings and also compare these outcomes within the group of patients with hematological malignancies.Methods: This retrospective study examines risk factors and outcomes of COVID-19 in patients with a history of cancer and laboratory-confirmed COVID-19 diagnosis between March 1 st, 2020, and December 31 st, 2020, at Rush University Medical Center, one of the largest COVID-19 tertiary care hospitals in Chicago. Baseline characteristics, malignancy type and types of cancer treatment within the last 30 days were recorded. Measures of COVID-19 severity included hospital admission versus outpatient care, use of oxygen, intensive care unit (ICU) admission, and mechanical ventilation. The primary outcome was death. Statistical analysis was conducted using optimal discriminant analysis, a non-parametric exact machine-learning algorithm which identifies the relationship between independent and dependent variables that maximizes model predictive accuracy adjusted to remove the effect of chance. Analysis was performed separately for each attribute using the entire sample (“training” analysis), then one-sample jackknife analysis was conducted to estimate cross-generalizability of findings using the model to classify an independent random sample.Results: 378 total patients with a history of cancer tested positive for COVID-19 within the time frame of the study. Of these, 294 (78%) patients had ST malignancy and 84 (22%) patients had HM. Characteristics and outcomes are summarized in Table 1. ST patients were marginally older than HM patients (p<0.025). A significantly greater proportion of HM patients were male (p<0.0023). HM and ST patients did not differ with respect to percentage receiving active cancer treatment (p<0.81). Compared to ST patients, more HM patients had received corticosteroids in the 30 days prior to COVID-19 diagnosis (p<0.017), had higher rates of hospitalization (p<0.0013) and ICU requirement (p<0.0001) with a significantly longer length of ICU stay (p<0.0036). Compared to ST patients, HM patients also required oxygen (p<0.002) and mechanical ventilation (p<0.0005) more often and had a 3.88-fold statistically higher death rate (OR 3.88 [95% CI 1.62-9.29] p<0.003). Patients with HM are categorized by disease subtype and summarized in Table 2. The case fatality rate from COVID-19 was 33.3% for patients with myeloproliferative neoplasms/myelodysplastic syndromes (MPN/MDS), 21.4% for patients with chronic lymphocytic leukemia (CLL), 13.6% for patients with non-Hodgkin lymphoma, 10.5% for patients with plasma cell neoplasms, and 4.5% for patients with acute leukemia. When looking at outcomes, CLL had the highest percentage of patients requiring hospital admission, oxygen, and ICU admission, and MPN/MDS had the highest percentage of patients requiring mechanical ventilation.Conclusions: Patients with hematologic malignancies had more severe COVID-19 illness and hospitalization rates and a 3.88-fold higher rate of death than patients with solid tumors. The comparable proportion of patients on anti-cancer therapy despite differences in survival suggests that being on anti-cancer therapy is less important than the underlying diagnosis of HM versus ST as a determinant of poor outcomes. Clinicians should closely monitor and initiate early COVID-19 treatments for all patients with HM and COVID-19. Because HM are highly heterogenous group of cancers, it is important to look at subtypes in greater detail. Numerous patient-level, disease-specific, and therapy-related factors may impact outcomes of COVID-19 among patients with HM, and we are currently analyzing additional data to better understand the factors which make this disease group more susceptible to severe infection. [Display omitted] DisclosuresKuzel: Sanofi-Genzyme Genomic Health Tempus laboratories Bristol Meyers Squibb: Honoraria; Genomic Health: Membership on an entity's Board of Directors or advisory committees; Exelixis: Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other; Curio Science: Membership on an entity's Board of Directors or advisory committees; AmerisourceBergen Corp: Membership on an entity's Board of Directors or advisory committees; CVS: Membership on an entity's Board of Directors or advisory committees; Tempus Laboratories: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Other: Data Monitoring Committee Membership; Amgen: Other: Data Monitoring Committee Membership; SeaGen: Other: Data Monitoring Committee Membership; Medpace: Other: Data Monitoring Committee Membership.

COVID Vaccine Antibody Responses in Patients with Hematologic Malignancies in a Myeloid Enriched Cohort: A Better Antibody Response in Patients with Myeloid Malignancies Than B-Cell Malignancies

Background:The risk of severe COVID-19 is increased in patients (pts) with hematologic malignancies, with a reported risk of death of 34% (Vijenthira et al, 2020). The ASH-ASTCT COVID-19 vaccine guidelines indicate that certain immunocompromised patient populations could have an attenuated response to the SARS-CoV-2 vaccine. However, most SARS-CoV-2 vaccine trials required pts to be off immune suppression to be eligible and therefore excluded most pts with hematologic malignancies. Little is known about the efficacy of SARS-CoV-2 vaccines in pts with hematologic malignancies. In this study, we aimed to evaluate the serological response of Pfizer and Moderna vaccination after two doses given in pts with hematologic malignancies with a focus on pts with myeloid malignancies.Methods:Patients with a history of hematologic malignancies treated at the University of Texas Southwestern Medical Center and received two doses of vaccination with quantitative measurement of SARS-CoV-2 IgG Spike antibody to assess vaccination response were included in this study. Baseline patient and disease characteristics including disease status and therapy given at the time of vaccination were collected. Time to vaccine response was defined as having a positive quantifiable spike IgG antibody titer per the lab reference range. The development of COVID-19 infection as well as antibody titer levels were collected. Categorical variables were compared using Chi-square and Fisher's exact tests and student t-test and ANOVA test were used to compare continuous variables.Results:A total of 61 pts with hematologic malignancies had spike IgG antibody testing after receiving 2 doses of the vaccine were included in this study. The median age at the time of vaccination was 72 (22-85) and 46% of pts were female. Eighty five percent of pts were Caucasian. The majority of pts (67.3%) had a myeloid malignancy (MDS/CMML 29.5%, AML 14.8%, myelofibrosis 16.4%, CML 6.6%), followed by chronic lymphocytic leukemia (16.4%), and others (6.6%). The median time from hematologic malignancy diagnosis to the first vaccine dose was 51 months (0.4-337 months). At the time of vaccine administration, 46 (75%) of pts were on active therapy and 39 (64%) of pts had active disease. Median time from the second vaccine dose to IgG spike antibody testing was 64 days (26-268 days). Most pts (75%) mounted a serological response with quantifiable COVID-IgG spike antibodies, 85% and 56% in myeloid and lymphoid malignancy, respectively. All pts with MDS/CMML/CCUS and CML mounted an immune response (100%), followed by acute myeloid leukemia (n: 7/9, 78%) and myelofibrosis (n: 6/10, 60%). Eight (13%) of pts were receiving hypomethylating agent therapy at the time of vaccination and all (100%) had a positive IgG response. Only one patient developed COVID-19 infection post vaccination with a documented IgG response and 2 pts had COVID-19 infection prior to the first dose of vaccination, both of these pts had IgG titers >10,000. Sixty percent of pts (9/15) with negative IgG response received treatment with either CD20 monoclonal antibodies or BTK inhibitors within 12 months of the first vaccine dose. Two out of three pts (67%) receiving Ruxolitinib had negative serology. Seven pts were on treatment with hydroxyurea, interestingly, all but the 2 pts with polycythemia vera had a negative antibody titer while on treatment with hydroxyurea. There was a strong positive correlation between vaccine titer and absolute lymphocyte count (r 2=0.27, p<0.001) (Figure).Conclusions:In this retrospective study, we demonstrate a higher rate of COVID-19 vaccine efficacy in pts with myeloid malignancy with varying responses per treatment and disease subtype compared to pts with B-cell malignancy with variable anti-CD20 or BTK inhibitor therapy. Pts with myelodysplastic syndromes, overlap syndromes of clonal cytopenia of undetermined significance all developed spike antibodies irrespective of hypomethylating therapy or Hydrea as did pts with chronic myeloid leukemia. However, pts with polycythemia vera and those on treatment with Ruxolitinib had an attenuated response to the vaccine. Albeit this single center study, pts with myelodysplastic syndromes should be offered COVID vaccines irrespective of their blood counts or ongoing treatment. Our findings should be validated in a larger group of patients. [Display omitted] DisclosuresPatel: Agios: Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Membership on an entity's Board of Directors or advisory committees; PVI: Honoraria. Anderson: Celgene, BMS, Janssen, GSK, Karyopharm, Oncopeptides, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Awan: Cardinal Health: Consultancy; BMS: Consultancy; Dava Oncology: Consultancy; Karyopharm: Consultancy; Merck: Consultancy; Johnson and Johnson: Consultancy; Incyte: Consultancy; Beigene: Consultancy; Verastem: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; Kite pharma: Consultancy; Gilead sciences: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; ADCT therapeutics: Consultancy; Astrazeneca: Consultancy; Genentech: Consultancy. Madanat: Blue Print Pharmaceutical: Honoraria; Onc Live: Honoraria; Stem line pharmaceutical: Honoraria; Geron Pharmaceutical: Consultancy.

Telehealth Interventions for Supportive Management and Early Recognition of Treatment-Related Symptoms in Patients With Hematologic Malignancies.

Purpose:The purposes of this literature review were to (1) establish the utility of supportive telehealth interventions focusing on early identification of treatment-related symptoms in adult patients with hematologic malignancies, with a secondary aim to (2) evaluate acceptability and feasibility.Methods:A literature review was conducted using PubMed, Cochrane Database of Systematic Reviews, CINAHL, Scopus, and Embase. Dates searched were from January 2007 through December 2019. Inclusion criteria included a diagnosis of hematologic malignancy, incorporation of telehealth interventions, effects on physiological outcomes, and participants ages 18 or older. Articles were excluded if they were a duplicate, had an irrelevant title, or were an incomplete study.Results:Results indicated overall utility, acceptability, and feasibility of the interventions, including improved awareness of late and long-term therapy–related sequelae in survivorship, an overall decline in the number of chemotherapy delays with decreased rates in dose reductions, a means to further manage exercise remotely, and finally, improved communication between provider and patient with real-time management of acute and chronic treatment-related side effects using supportive telemetric interventions.Conclusion:Overall, the use of telehealth interventions in adult patients with hematologic malignancies positively impacts patient health, and telehealth interventions were found to be both accepted and feasible. Future studies should be directed at the role and involvement of the advanced practitioner, and current literature calls for well-planned studies as methodologic limitations remain in the evidence.

A Machine Learning Approach to the Classification of Acute Leukemias and Distinction From Nonneoplastic Cytopenias Using Flow Cytometry Data.

Flow cytometry (FC) is critical for the diagnosis and monitoring of hematologic malignancies. Machine learning (ML) methods rapidly classify multidimensional data and should dramatically improve the efficiency of FC data analysis. We aimed to build a model to classify acute leukemias, including acute promyelocytic leukemia (APL), and distinguish them from nonneoplastic cytopenias. We also sought to illustrate a method to identify key FC parameters that contribute to the model's performance. Using data from 531 patients who underwent evaluation for cytopenias and/or acute leukemia, we developed an ML model to rapidly distinguish among APL, acute myeloid leukemia/not APL, acute lymphoblastic leukemia, and nonneoplastic cytopenias. Unsupervised learning using gaussian mixture model and Fisher kernel methods were applied to FC listmode data, followed by supervised support vector machine classification. High accuracy (ACC, 94.2%; area under the curve [AUC], 99.5%) was achieved based on the 37-parameter FC panel. Using only 3 parameters, however, yielded similar performance (ACC, 91.7%; AUC, 98.3%) and highlighted the significant contribution of light scatter properties. Our findings underscore the potential for ML to automatically identify and prioritize FC specimens that have critical results, including APL and other acute leukemias.