Hematology Practice Research Articles

Considerations for the Management of Oncology Patients During the COVID-19 Pandemic.

Worldwide incidence and mortality due to the coronavirus disease 2019 (COVID-19) pandemic is greatest in the United States, with the initial epicenter in New York. In Nassau County, New York, where we practice, our institution has had more than 2500 cases and has discharged from the hospital more than 1000 patients. As many academic and private institutions have swiftly shifted their clinical and research priorities to address the pandemic, data are emerging regarding both the impact of malignancy on COVID-19 outcomes as well as the challenges faced in assuring that cancer care remains unimpeded. Of concern, recent studies of cancer patients primarily in China and Italy have suggested that advanced malignancy is associated with increased susceptibility to severe COVID-19 infection. At present, more than 500 clinical trials are underway investigating the pathogenesis and treatment of COVID-19, including expanded use of oncology drugs, such as small molecular inhibitors of cytokine pathways. Here, we begin by reviewing the latest understanding of COVID-19 pathophysiology and then focus our attention on the impact of this virus on hematologic and oncologic practice. Finally, we highlight ongoing investigational treatment approaches that are so relevant to the care of oncology patients during this extraordinary pandemic.

A CASE OF HENOCH-SCHONLEIN PURPURA ASSOCIATED WITH TUBERCULOUS PLEURISY

SESSION TITLE: Fellows Chest Infections Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Herein we describe a case of Henoch-Schönlein purpura (HSP) associated with tuberculous pleurisy. Complications of these two conditions are extremely rare [1,2]. It has been thought that HSP may be triggered by tuberculosis or by antituberculous treatment. This case highlights the importance of recognizing that HSP can occur during antituberculous treatment. CASE PRESENTATION: An 86-year-old male visited the previous hospital for dyspnea on exertion and fever for 5 days. Chest X-ray revealed left-sided pleural effusion, and he was referred to our department. Chest CT revealed left-sided pleural effusion and calcified nodule in the superior segment of the left lung. Thoracentesis revealed exudative pleural effusion with lymphocyte fraction of 75%. Pleural fluid ADA level was 121.4 IU/L and T-spot TB test was positive. The patient was clinically diagnosed with tuberculous pleurisy because he refused pleural biopsy. Antituberculous treatment with ethambutol /isoniazid/rifampicin was started. 17 days after the initiation of the treatment, systemic eczema and blurred eyes developed, and all drugs were discontinued. These symptoms gradually improved, but palpable purpura appeared in both lower limbs. HSP was suspected and skin and renal biopsy was performed. Pathological examination of the skin revealed leukocytoclastic vasculitis of small vessels without IgA deposition. Pathological examination of the kidney revealed diffuse proliferation of mesangial cells and matrix, endocapillary proliferation, segmental necrotizing lesions, and cellular crescents. Moreover, IgA deposition in mesangium was observed. From these findings, the patient was diagnosed with HSP, and systemic steroid therapy was started. After the steroid treatment, purpura disappeared and urinary protein decreased, so antituberculous drugs were restarted from a small dose. Since then, the dosage of antituberculous drugs has been gradually increased, and treatment can be continued even now. DISCUSSION: HSP is a leukocytoclastic vasculitis that usually affects children. Some precipitating factors have been reported as follows: infections, drugs, malignancy, environmental chemicals, insect bites, trauma, and complement C2 deficiency [1]. HSP is considered as an IgA-mediated immune vasculitis, and palpable purpura is regarded as essential for diagnosis. HSP is rare in adults, but more severe [2]. To the best of our knowledge, there have been 13 cases of HSP associated with tuberculosis [3]. It has been reported that not only tuberculosis but also antituberculosis drugs can cause HSP. In our patient, symptoms of HSP occurred after the initiation of antitubeculous treatment and improved with discontinuation of the drugs and addition of steroids. Therefore, we suspected that HSP was triggered by antituberculous drugs. CONCLUSIONS: This case highlights the importance of recognizing that HSP can occur during antituberculous treatment. Reference #1: 1.Catherine PM, Hayward. Clinical approach to patient with bleeding and bruising. In: Hoffman R, Furie B, McGlave P, Silberstein LE, Shattil SJ, Benz EJ, Heslop H. Hematology basic principles and practice. Philadelphia: Elsevier Saunders publications; 2013. p 1847-56. Reference #2: 2.Laxer RM, Benseler SM. Pediatric Systemic Lupus Erythematosus, Dermatomyositis, Scleroderma, and Vasculitis. In: Firestein GS, Budd RC, Harris ED, McInnes IB, Ruddy S, Sergent JS. Kelley's Textbook of Rheumatology; 9th Ed; vol II. Philadelphia: W.B. Saunders Co, 2000: pp 1171-800. Reference #3: 3.Seth G, Rohatgi A, and Kumar G. Henoch-Schonlein Purpura: An unusual presentation of Disseminated Tuberculosis. Indian Journal of Basic and Applied Medical Research; September 2015: 4; 476-481. DISCLOSURES: No relevant relationships by Yuri Hiramatsu, source=Web Response No relevant relationships by Kazunori Tobino, source=Web Response

FEATURES OF CAPILLARY BLOOD FLOW IN PATIENTS WITH PATHOLOGY OF INTRANASAL STRUCTURES AND NASAL BREATHING DISORDERS

The investigation of the vascular microcirculation system is important for diagnosis, assessment of the severity and nature of pathological processes in human body, monitoring the effectiveness of treatment. Monitoring the state of microcirculation in impaired respiratory function of the nose helps to study the subtle mechanisms of regulation of vascular−tissue relations. To do this, there were used the biomicroscopic methods to study capillary blood flow, one of the most relevant and promising is optical capillaroscopy of the nail bed. This method makes it possible to identify at the evidence level the peculiarities of the functioning of the peripheral circulatory system by the state of the capillary system and to evaluate the effectiveness of treatment by the rheological properties of blood in hematological practice. There were examined 145 patients by means of computer capillaroscopy to study the rate of capillary circulation in the patients with pathology of intranasal structures and nasal breathing disorders. All patients underwent a complete clinical examination, routine instrumental examinations, and computer capillaroscopy using a video capillaroscope with a visual magnification of up to 550 times. The obtained images were stored and processed according to a special software. During the characterization of the capillaroscopic picture there were evaluated: pathological tortuosity, change in the caliber of arterioles and venules, disorganization of the capillary network, the number of functioning capillaries. Changes in the speed and nature of capillary blood flow (accelerated, slow, stasis) were observed. The optical capillaroscopy method allows not only to visually assess the condition of microvessels, but also to determine such an important parameter as blood circulation, actually, it can replace the study of laser Doppler. Such data will be important in the diagnosis of respiratory and olfactory disorders and the formation of adequate tactics for their treatment. Key words: microcirculation, microcirculatory tract, capillary circulation, nasal obstruction, nasal breathing disorders, pathology of intranasal structures, computer capillaroscopy.

Disease management of patients with immune thrombocytopenia\u2014results of a representative retrospective survey in Germany

Clinical research has resulted in an improvement of treatment options for patients with immune thrombocytopenia (ITP) over the last years. However, only few data exist on the real-life management of patients with ITP. To expand the knowledge, a multicenter, national survey was undertaken in 26 hematology practices distributed all over Germany. All patients with a diagnosis of ITP were documented using questionnaires, irrespective of the diagnosis date over a period of 2 years. Overall, data of 1023 patients were evaluated with 56% of patients being older than 60 years. Seventy-nine percent of the patients had chronic (> 12 months), 16% persistent (> 3–12 months), and 5% newly diagnosed (0–3 months) ITP. In 61% of cases, the disease lasted 3 or more years before survey documentation started. Main strategies applied as first-line therapy consisted of steroids in 45% and a “watch and wait” approach in 41% of patients. During second- and third-line strategies, treatment with steroids decreased (36% and 28%, respectively), while treatment modalities such as TPO-RAs increased (19% and 26%, respectively). As expected, patients with a low platelet count and thus a higher risk for bleeding and mortality received treatment (esp. steroids) more frequently during first line than those with a higher platelet count. Up to a third of patients were treated with steroids for more than a year. Overall, our study provides a cross-section overview about the current therapeutic treatment landscape in German ITP patients. The results will help to improve therapeutic management of ITP patients.

Reform and Practice of Clinical Teaching of Hematology

Hematology is a highly specialized subject in internal medicine, including complex theoretical knowledge and practical courses, such as Blood Testing. Clinical internship is a challenge that medical students must face, but the theoretical basis for learners , initiatives and teaching methods, quality and other requirements are quite high. The actual clinical teaching of blood diseases are facing great challenges in these areas. On the basis of analyzing the current dilemma faced by the clinical teaching of hematology, this article explores the reform of clinical practice in hematology from the aspects of optimizing content, increasing students 'practical interest, reforming teaching methods, improving teachers' quality, and using online platforms Methods and approaches.

Studies on inherited platelet disorder: a systematic review

Objective The aim was to review the studies on clinical presentation, diagnosis, and management of inherited platelet disorder (IPD). Materials and methods A systematic search of MEDLINE (PubMed, Medscape, Science Direct, EMF-Portal) and internet was conducted on all articles published from 1997 to 2016. English language reports of perianal fistula were assessed. The initial search presented 150 articles where 26 satisfied the inclusion criteria. Articles not reporting on IPD in the title or abstract were not included. A total of 11 independent investigators extracted data on methods. Comparisons were made by structured review, with the results tabulated. Eight authors emphasized clinical presentation of IPD, nine about diagnosis of IPD, and nine about management of IPD. Findings Common symptoms include ecchymosis, epistaxis, menorrhagia, and excessive bleeding with childbirth, surgery, dental procedures, and trauma. IPD diagnosis is straightforward in the major platelet function disorders such as Bernard-Soulier Syndrome (BSS) and Glanzmann thrombasthenia (GT). Establishing a conclusive molecular diagnosis is the bedrock of good hematological practice, because it informs optimal treatment and can provide clarity about disease progression. The management of patients with IPDs usually consists of general measures aimed at avoiding bleeding and the use of supportive therapy to control hemorrhagic episodes. Conclusion IPDs are important causes of bleeding that can quantitatively and qualitatively alter platelets, impairing their function. The management of patients with IPDs usually consists of general measures aimed at avoiding bleeding and the use of supportive therapy to control hemorrhagic episodes. Moreover, patients and their parents must be instructed about drugs that impair platelet functions.

Patient satisfaction after conversion from warfarin to direct oral anticoagulants for patients on extended duration of anticoagulation for venous thromboembolism - The SWAN Study.

BackgroundWarfarin is an anticoagulant medication proven effective in the initial treatment and secondary prevention of venous thromboembolism. Anti-Xa direct oral anticoagulants are alternatives to warfarin; however there is limited data assessing satisfaction after switching from warfarin to an anti-Xa direct oral anticoagulant in patients for treatment of venous thromboembolism.ObjectivesTo assess medication satisfaction in patients requiring anticoagulation for venous thromboembolism after conversion from warfarin to an anti-Xa direct oral anticoagulant.MethodsA retrospective cohort study with prospective assessment of satisfaction and review of adverse events following anti-Xa direct oral anticoagulant replacement of warfarin for treatment of venous thromboembolism. Out of 165 patients who had switched from warfarin to rivaroxaban or apixaban from an outpatient haematology practice, 126 patients consented for a survey of patient’s relative satisfaction of anti-Xa direct oral anticoagulant therapy compared with previous warfarin therapy using the Anti-Clot Burden and Benefits Treatment Scale and SWAN Score.ResultsThe mean Anti-Clot Burden and Benefits and SWAN Score was 93% (56/60) and 83% (24.8/30) respectively reflecting high satisfaction with anti-Xa direct oral anticoagulants. 120 patients stated preference for anti-Xa direct oral anticoagulants over warfarin. Leading perceptions driving this was the reduction in frequency of medical contact and fewer bleeding side effects. Thirteen patients (10.3%) experienced an adverse event after the anti-Xa direct oral anticoagulant switch (majority were non-major bleeding) but most remained on anti-Xa direct oral anticoagulant treatment after management options were implemented with continued high satisfaction scores.ConclusionsPatient satisfaction with anti-Xa direct oral anticoagulant therapy for the treatment and prevention of venous thromboembolism after switching from warfarin in routine clinical practice appeared high. Improved patient convenience including reduced frequency of medical contact and fewer unpredictable side effects were perceived as significant advantages of anti-Xa direct oral anticoagulants compared to warfarin.

Mayo Clinic Hematology Fellowship for Advanced Practice Providers

Advanced practice providers (APPs), including nurse practitioners (NPs) and physician assistants (PAs), are part of a growing cancer care workforce. Current hematology-specific education provided by most graduate NP and PA school educations is limited. Mayo Clinic School of Health Sciences launched a hematology-specific fellowship in 2018 to provide APPs with the skills and knowledge required to deliver high-quality specialty care in hematology and blood and marrow transplant (BMT). The fellowship curriculum was developed based on a needs-based assessment study as well as the qualitative reported experiences of current hematology-specific APPs. The curriculum contains didactic in-class education, research opportunities, and mentored clinical rotations in both inpatient and outpatient practice in hematology and BMT. This 12-month fellowship, one of the only postgraduate training programs dedicated to benign and malignant hematology practice, provides structured training for highly qualified graduate APPs interested in developing a rewarding career in hematology.

Artificial Intelligence in Hematology: Current Challenges and Opportunities

Artificial intelligence (AI), and in particular its subcategory machine learning, is finding an increasing number of applications in medicine, driven in large part by an abundance of data and powerful, accessible tools that have made AI accessible to a larger circle of investigators. AI has been employed in the analysis of hematopathological, radiographic, laboratory, genomic, pharmacological, and chemical data to better inform diagnosis, prognosis, treatment planning, and foundational knowledge related to benign and malignant hematology. As more widespread implementation of clinical AI nears, attention has also turned to the effects this will have on other areas in medicine. AI offers many promising tools to clinicians broadly, and specifically in the practice of hematology. Ongoing research into its various applications will likely result in an increasing utilization of AI by a broader swath of clinicians.

Chronic fatigue syndrome in the routine hematology practice

Purpose. Presentation of clinical signs and laboratory profiles of the patients with chronic fatigue syndrome, and comparison of their symptoms with those of the patients with iron deficiency anemia.
 Materials and methods. Retrospective analysis of the patients symptoms referred to the hematologist outpatient clinic during the period between January 2016 and December 2018.
 Results. There were 560 patients(162 males and 398 females) referred for a primary consultation by a hematologist. Median age was 52.5 (1894) years. The unexplained fatigue was reported by 27 (4.8%) patients (1 male and 26 females), median age 41 (2466) years. Diagnosis chronic fatigue syndrome (CFS) was confirmed based on the criteria in 17 (63%) patients. 10 patients (47%) with symptoms partially meeting the criteria were diagnosed idiopathic fatigue syndrome (SIF). Half of the patients connected the onset of the diseases with emotional trauma (family issues etc.). The prevailing complaints (30%) were represented by: prolonged fatigue, mild memory impairment and distraction, arthralgia and insomnia. The most frequent reason to see a hematologist was fatigue and borderline changes in the blood tests. Five patients with CFS and 2 patients with SIF were known to have previously diagnosed iron deficient anemia (IDA). Median level of hemoglobin in the patients with severe fatigue and IDA was 10.7 (8.411.7) g/dl. Median follow up duration was 28 (640) months. In the observed group (n = 23) 17% of the patients (n = 4) showed spontaneous improvement. The rest of the patients had reported no changes. The comparison group (n = 64) included the patients with IDA. Most of them (n = 38) did not report fatigue as their initial symptoms (median level of hemoglobin was 9.35 (5.511.9) g/dl). Twenty six patients reported fatigue; median level of hemoglobin was 8.15 (5.911.7) g/dl. The difference between the hemoglobin levels in two groups was significant (р 0.05). However, there was no correlation between the level of hemoglobin and fatigue in the patients with CFS and SIF. The correlation was found in the patients with CFS and SIF between fatigue and patients perception.
 Conclusion. The main symptoms accompanying CFS are fatigue and other non-specific symptoms which are often related to patients emotional status. Considering CFS as a differential diagnosis when dealing with fatigue is essential.

Nurses' Experiences When Introducing Patient-Reported Outcome Measures in an Outpatient Clinic: An Interpretive Description Study.

Application of patient-reported outcome measures (PROM) seems to be a step toward person-centered care and identifying patients' unmet needs. To investigate the experiences of nurses when PROMs were introduced in a hematological clinical practice as part of a multimethod intervention study. The qualitative framework was guided by the interpretive description (ID) methodology, including a focused ethnographic approach with participant observations and interviews. The instruments introduced were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Outcomes and Experiences Questionnaire. Analysis was inspired by Habermas' critical theory. The analysis revealed 2 predominant themes of nurses' experiences: "PROMs are only used when there is time-which there rarely is" and "PROMs cannot be used without a strategy, just because they are present." Nurses' experiences with PROMs depended on the systems' rationale, resulting in limited capacity to use and explore PROMs. Nurses believed that PROMs might have the potential to support clinical practice, as PROMs added new information about patients' conditions but also identified needs within supportive care, leaving the potential of PROMs uncertain. Simply introducing PROMs to practice does not necessarily actuate their potential because use of PROMs is dependent on institutional conditions and mandatory tasks are prioritized. This study contributes knowledge of nurses' experiences when introducing PROMs in a hematological outpatient clinical practice. Findings can guide future PROMs research within the field of nursing.

Platelet Counting: Ugly Traps and Good Advice. Proposals from the French-Speaking Cellular Hematology Group (GFHC).

Despite the ongoing development of automated hematology analyzers to optimize complete blood count results, platelet count still suffers from pre-analytical or analytical pitfalls, including EDTA-induced pseudothrombocytopenia. Although most of these interferences are widely known, laboratory practices remain highly heterogeneous. In order to harmonize and standardize cellular hematology practices, the French-speaking Cellular Hematology Group (GFHC) wants to focus on interferences that could affect the platelet count and to detail the verification steps with minimal recommendations, taking into account the different technologies employed nowadays. The conclusions of the GFHC presented here met with a "strong professional agreement" and are explained with their rationale to define the course of actions, in case thrombocytopenia or thrombocytosis is detected. They are proposed as minimum recommendations to be used by each specialist in laboratory medicine who remains free to use more restrictive guidelines based on the patient’s condition.

The Value of Next-Generation Sequencing in the Screening and Evaluation of Hematologic Neoplasms in Clinical Practice.

The implementation of next-generation sequencing (NGS) in routine clinical hematology practice remains limited. We evaluate the clinical value of NGS in the screening, diagnosis, and follow-up in hematologic neoplasms. A targeted NGS panel was used to assess a total of 178 patients for questionable or previously diagnosed myeloid neoplasms. Gene variants were identified in 53% of patients. Novel variants were identified in 29% of patients and variants of unknown significance in 34%. Bone marrow samples yielded a higher number of variants than in peripheral blood. NGS is a more sensitive test than conventional cytogenetics. In several cases, NGS played a key role in the screening, diagnostics, prognostic stratification, and the clinical follow-up of a wide variety of myeloid neoplasms. NGS is an effective tool in the evaluation of suspected and confirmed hematologic neoplasms and could become part of the routine workup of patients.

Diagnostic Utility of Bone Marrow Aspiration and Bone Marrow Biopsy in Hematological Practice

Diagnostic Utility of Bone Marrow Aspiration and Bone Marrow Biopsy in Hematological Practice

Quality Improvement Initiatives to Improve Transfusion Safety and Efficiency for Patients Receiving Daratumumab

Introduction: Daratumumab is an IgG1k monoclonal antibody directed against CD38, a surface glycoprotein expressed on several cell types including erythrocytes and B lymphocytes at various stages in development, including bone marrow precursors and plasma cells. It was initially approved by the FDA in 2015 for the treatment of multiple myeloma and has since garnered additional approvals in other settings leading to a growing number of patients receiving daratumumab. Its anti-B lymphocyte properties are therapeutic in myeloma patients; however, it also binds CD38 on erythrocytes and circulates for up to six months after a dose. This creates a long-term problem when caring for these patients regarding transfusion needs and resources. In particular, daratumumab causes antibody screens to be panreactive, potentially masking the presence of clinically relevant antibodies. Mitigation of this effect requires specialized treatment with dithiothreitol (DTT)-treated reagent erythrocytes to release CD38 from the cell membrane. This step allows for more accurate detection of clinically relevant antibodies, with the noted exception of the Kell system as these antigens are also removed. Methods: When daratumumab was placed on formulary, we started weekly communication between the laboratory and clinical teams in order to establish best institutional practices. Additionally, a list of patients on daratumumab was created in order to track them across the institution and measure the impact of interventions on their care. These have prompted multiple interventions to improve the safety and efficiency of patients on daratumumab receiving transfusions. Results: As of January 2018, our laboratory began implementing in-house DTT testing and eliminated the need to send patient samples to a reference laboratory. Beginning in January 2019, DTT-antibody screens (ABSC) were captured in the electronic medical record (EMR). Over the next six months, 173 distinct DTT-ABSC were performed on 41 patients. Of these, 13 received at least one RBC transfusion for a total of 41 units, with 12 (29%) occurring as an outpatient and 29 (71%) as an inpatient. Importantly, all of these transfusions were on the same-day of the DTT-ABSC, reducing the burden of time and cost associated with travel, as well as the morbidities of delayed transfusion. This is a major step forward in patient care as there were previously no "same-day" transfusions when DTT-ABSC was sent to a reference laboratory. The previous reference laboratory turnaround time averaged 1165 minutes compared with 186 minutes for the in-house testing. These initiatives have also resulted in educational efforts, such as the creation of a daratumumab-specific transfusion consent form to be signed by the attending hematologist at the time of starting therapy, outlining the challenges associated with identifying blood for transfusion and documenting that the benefits of transfusion outweigh the potential risks. This form is valid indefinitely and has subverted previous clinical scenarios where inpatients on daratumumab required urgent/emergent transfusion without an in-house hematologist available to consent for the transfusion. Because DTT also eliminates Kell antigens, clinically relevant antibodies may go undetected in samples treated with DTT. Thus, it is our policy to use Kell-negative products for patients who are on daratumumab, unless the patient expresses the Kell antigen. Conclusions/Future Directions: Daratumumab therapy is becoming increasingly common in hematology practice. Awareness of the laboratory and clinical challenges that accompany its use and working to mitigate them will lead to safer and more timely patient care. In particular, in-house DTT-ABSC has led to same-day results and transfusion on the same outpatient visit. Next steps include additional educational efforts at an institutional level, establishing simple algorithms within the EMR linked with the order for daratumumab (e.g., automatic ABSC prior to administration), and refining our tracking system to better assess future interventions. Disclosures No relevant conflicts of interest to declare.

Symptom Assessment in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms at an Academic Medical Institution

Symptom Assessment in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms at an Academic Medical Institution

Very High Seroprevalence of CMV and EBV Among a Large Series of Patients with Hematological Malignancies at a Tertiary Care Center in Saudi Arabia - a Case for Investigating Cooperativity of Viruses in Carcinogenesis?

Background: Hematology practice in developing countries has some unique issues including a higher prevalence of infectious disease markers. Epstein-Barr virus (EBV) is an oncogenic virus and implicated in Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma and leiomyosarcoma in the immunocompromised (Ito Y et al. 2009). Cytomegalovirus (CMV) infection/reactivation in patients with hematological malignancies causes serious morbidity and mortality. Saudi Arabia is a high income rapidly developing country, but seroprevalence of CMV and EBV is reportedly higher compared to developed countries (Ghazi 2002, Seale et al., 2006, Joseph et al., 2005). EBV & CMV co-infection is not infrequent & occurs most commonly in the immunocompromised host. A significantly higher prevalence of antibodies (Abs) against CMV & EBV in some disease groups compared to controls has been reported from the same communities (Ocak et al., 2006, Al-Hakami et al., 2016). Interestingly, CMV disease occurrence in sibling donor hematopoietic stem cell transplant (HSCT) is infrequent in our area in spite of the occurrence of CMV reactivations (Aljurf et al., 2009, Saovic et al., 1999). Hence, knowledge of seroprevalence of these viruses in hematological malignancies may be helpful in strategic planning for transplants & transfusions. It may help in establishing any plausible etiological linkage with certain hematological malignancies. Methods: We retrospectively examined the records of adult patients (>14 years) with hematological malignancies for CMV and EBV status (IgG and IgM Abs by chemiluminescence immunoassay). We identified 2,007 patients (1104 males and 903 females) and grouped them according to gender along with broad hematological malignancy categories (Table 1). We tried to establish if any disease category had extraordinary seropositivity for CMV (IgG ≥20 U/ml) or EBV (IgG ≥12 U/ml). We also studied the prevalence of IgM Abs in those tested positive for IgG Abs. Results: Of 2,007 patients (males significantly more than females, p = 0.001), age range 14-93 year (mean 47.2), 503 underwent testing for CMV status and 520 for EBV. Among these tested patients, there was no significant gender difference as 96.1% males were CMV positive, and 95.4% females were CMV positive. On the other hand, 96.9% males were EBV IgG Abs positive compared to 92.5% of females, which was 2.56 (95% CI; 1.12 - 5.96) times more likely to be positive in the studied male patient population (p = 0.021). Overall seroprevalence for CMV IgG Abs was 95.4%, and for EBV IgG Abs it was 95% (Table 1). Among those with CMV IgG Abs, 25/482 (5.1%) had very high antibodies titer (>180 U/ml), and 23/25 patients (92%) had lymphoid malignancies (11 NHL, 7 HL, 2 ALL, 3 MM) and 2 had CML. Among those with EBV IgG Abs 59/495 (11.9%) had very high antibodies titer (>750U/ml); and 46/59 (77.97%) of these patients had lymphoid malignancies (20 HL, 16 NHL, 6 ALL, 4 CLL, 1 MM) and 13/59 (22.03%) had myeloid neoplasms (6 AML, 5 CML, 1 MDS, 1 MPN). Six patients had very high titers for both EBV and CMV antibodies. In CMV IgG Abs positive patients only 1.03% (5/482) had IgM antibodies, and in EBV IgG Abs positive only 2.22% (11/495) had IgM antibodies. Table 1 shows the prevalence across the gender and in different disease categories. The highest seroprevalence for CMV was found in CLL, multiple myeloma and MDS patients (100%); and for EBV it was highest in MDS and MPN patients (100%). Relatively lower seroprevalence of EBV was noted in ALL patients group (86.2%), and lower seroprevalence of CMV was noted in MPN patients group (87.5%). However, overall, there was no significant difference across the disease categories for either CMV (p = 0.362) or EBV (p = 0.114). Conclusions: In this large study on our patients with hematological malignancies, we report very high seroprevalence of CMV and EBV Abs, reaching up to 100% in some disease categories. Among those with very high titer of EBV IgG Abs, the majority had lymphoid malignancies. Short of establishing any etiological linkage, we noticed 100% of MDS patients had both CMV and EBV Abs. Contrary to other reports, our male patients were more likely to be EBV positive compared to the females. Our results support the need for further studies to investigate possible cooperative linkage of EBV and CMV in carcinogenesis. Disclosures No relevant conflicts of interest to declare.

Desideromastica: Tactile Chew Cravings in Iron Deficiency Anemia

Introduction: The compulsive craving and consumption of non-food substances, known as pica, is a well-documented symptom associated with iron deficiency anemia (IDA). Olfactory cravings associated with IDA are a recently described phenomenon known as desiderosmia. In our practice we observed a subset of patients with IDA who report specific tactile cravings associated with mastication. Methods: This study included patients from the Mayo Clinic (Rochester, MN) and Ankara Training and Research Hospital (Ankara, Turkey) Hematology practices who self-reported tactile mastication cravings during initial evaluation for IDA between 1/1/18 and 6/30/19. Information including sociodemographics, substance craved, values of hemoglobin (Hgb), mean corpuscular volume (MCV), and ferritin before and after iron replacement therapy, and symptom resolution after treatment were recorded. Results: We observed 12 patients with IDA who self-reported chew cravings during initial evaluation. All patients were female and the median age was 41.5 years (33-59). Of these 12 patients, median baseline Hgb, MCV, and ferritin were 9.4 g/dL (6.6-12.9), 73.7 fL (59.1-95.1), and 6 µg/L (2-21), respectively. Tactile cravings included chewing gum (3), mastic gum (2), ginseng (1), dry oats (1), crackers (1), pickles (1), chips (1), sawdust (1), and knitting rope (1). Many patients reported the frequency and satisfaction of these cravings resulted in jaw pain as well as the persistence of cravings despite this discomfort. Only 16.7% (2/12) reported concurrent ice pica. In total, 9 patients proceeded with observed treatment of their IDA with clinical follow-up and laboratory confirmation of iron repletion. Oral (ferrous glyconate or ferrous fumarate) and intravenous (ferric carboxymaltose, iron sucrose, or low molecular weight iron dextran) iron replacement were used in 33.3% (3/9) and 66.7% (6/9) patients, respectively. Post-treatment median laboratory values include: Hgb 12.7 g/dL (10.8-14.7), MCV 80.1 fL (76.1-91.7), and ferritin 98 µg/L (24-398). Overall, 88.9% (8/9) reported resolution of chew cravings after iron repletion. The lone patient with persistent symptoms had a baseline ferritin of 10 µg/L, improved to 398 µg/L after replacement, and settled back at 42 µg/L three months later. Discussion: Our patient experience provides suggestive evidence that oral tactile craving symptoms, distinct from ice pica, exists in a subset of patients suffering from IDA. For this, we propose the term "desideromastica" derived from the Latin words "desiderare" for desire and "mastica" for chew. "Desidero" can also be indicative of a reduction in iron, which relates to iron deficiency. Our hope in naming this relatively unexplored symptom associated with IDA will encourage additional clinicians to share their experience and guide future investigation. Disclosures No relevant conflicts of interest to declare.

Hematological Disorders in Human Patients with Son Mutations

Precise regulation of transcription and RNA splicing is critical for controlling hematopoietic cell fate determination and lineage differentiation. Alteration of expression of lineage-specific transcription factors and several core spliceosome components in hematopoietic malignancies highlight the significance of abnormal transcription and RNA splicing as disease-causing factors. Our group previously demonstrated that SON, a large nuclear speckle protein possessing dual abilities to bind both DNA and RNA, functions as a splicing factor as well as a transcriptional repressor. We recently identified heterozygous loss-of-function mutations in the SON gene from children with intellectual disability and developmental delay often with a broad spectrum of other congenital anomalies. The disorder caused by SON haploinsufficiency has been designated as ZTTK syndrome (Zhu-Tokita-Takenouchi-Kim syndrome; OMIM #617140). The majority of the mutations found in these patients are frameshift or nonsense mutations which cause degradation of the mutation-bearing transcript. While the most prominent features of these patients are brain malformations and musculoskeletal abnormalities, we identified various hematological disorders from children with ZTTK syndrome. Notable symptoms include bone marrow failure, severe anemia, immunoglobulin deficiency, thalassemia, polycythemia, polycythemia vera, stroke due to blood clots, and leukocytopenia. Apart from the ZTTK syndrome, SON is known to be upregulated in acute myeloid leukemia (AML) patients and is correlated to altered hematopoietic differentiation. To investigate how altered SON expression affects hematopoiesis, we generated a mouse line with the Son gene deleted specifically in the hematopoietic lineage. Homozygous deletion of Son in hematopoietic lineage led to embryonic lethality, indicating that SON expression in blood cells is indispensable during development. Mice with heterozygous deletion of Son in the hematopoietic lineage were viable and born without notable defects or sign of diseases. However, there is a significant decrease in bone marrow cellularity in the mice with heterozygous deletion of Son. Furthermore, Son haploinsufficiency decreased the size of the lineage negative (Lin-) cell population and short-term hematopoietic stem cell (ST-HSC) population with a concurrent increase in megakaryocyte/erythrocyte lineage-biased multipotent progenitors (MPP2) within hematopoietic stem/progenitor cells. These findings suggest that the level of Son expression potentially affects stem cell maintenance and MPP lineage bias, and the distortion of the subpopulation balance within hematopoietic stem/progenitors is possibly linked to multiple hematological disorders. Our ongoing analyses of hematopoiesis and gene expression changes using this mouse model will expand our knowledge about the role of SON in several hematological disorders and benefit clinical practice for ZTTK syndrome patients. Disclosures No relevant conflicts of interest to declare.

Assessment of Provider Practices Regarding Management of VTE in Pediatric Leukemia

The development of venous thromboembolism (VTE) is a known complication occurring in children with leukemia with a reported incidence ranging from 1 to 37% (Ghanem, et al, Pediatric Blood & Cancer, 2017) and can be a source of significant morbidity. Known risk factors for VTE include central venous catheter (CVC) use, thrombophilia, and certain medications, such as asparaginase (Caruso, et al, Blood, 2006.) Despite the known occurrence of VTE in this population, there are no leukemia-specific guidelines for VTE management. Anticoagulant use in children with frequent periods of thrombocytopenia and coagulopathy is not risk free. Various elements of management lack standardization and consensus among practitioners. Given that the majority of pediatric leukemia patients are treated according to standardized protocols, it may be beneficial to standardize anticoagulation care guidelines. Therefore, the primary objective of this study was to assess current practices regarding the management of VTE in the pediatric leukemia population. We performed a cross sectional, anonymous, electronic survey of members of the American Society of Hematology (ASH) who self-identified as focusing in pediatric hematology or pediatric hematology/oncology, and the pediatric subcommittee of VENUS (VTE Network of the Hemostasis and Thrombosis Research Society) using Qualtrics, a secure online survey tool. Survey items included questions on demographics and clinical practice. Respondents were excluded if they were not board certified/eligible, if they did not participate in patient care, or if they did not answer survey research questions. A $25 gift card incentive was offered anonymously. This study was approved by both the Weill Cornell Medicine and Northwell Health IRBs. Of 870 surveys distributed, 154 were submitted, giving a 17.7% response rate. Twelve surveys were excluded, leaving 142 surveys for final analysis. There was even distribution of years in practice and size of clinical program among respondents (Figure 1A). Most respondents identified as being in hematology or combined practice. 50% of responding physicians (n=136) reported treating CVC-associated VTE for 3 months. 92% of respondents (n=138) report repeating imaging of the VTE with 58% (n=124) repeating at 6 weeks, and 31% at 3 months. 40% of respondents (n=131) treat cerebral venous sinus thrombosis (CVST) for 3 months, followed by 24% treating for 6 months. 95% of respondents (n=131) repeat imaging for CVST and of these individuals, 40% repeat imaging at 6 weeks followed by 50% at 3 months. The most frequently utilized anticoagulant class was heparins (n=140); respondents also reported using the direct Xa inhibitors Rivaroxaban (21%) and Apixaban (14%). Within the group utilizing direct Xa inhibitors, those in practice the longest (≥16 years) had the highest percentage of use (Figure 1B.) When asked at what platelet counts they hold therapeutic anticoagulation (n=140), 39% of respondents chose 50 x 109/L, 33% chose 30 x 109/L, and 16% chose 20 x 109/L. One person chose 100, x 109/L, 11% said they did not hold anticoagulation for thrombocytopenia, and 2 respondents gave platelet transfusions rather than hold anticoagulation (one at a cutoff below 30 x 109/L and one below 50 x 109/L). While no significant associations were seen, the highest percentage among individual groups using a platelet cutoff of less than 50 x 109/L were among those in practice longest, and those in the largest centers (Figure 1C). The results of this survey revealed variation in practice among practitioners regarding VTE management and prevention. Despite the lack of data in this population, a number of physicians are using direct Xa inhibitors in children with leukemia for anticoagulation. Imaging is being done earlier than treatment is being discontinued, potentially implying it is being used to monitor for progression, rather than help guide duration of therapy. Our survey had some limitations, including the low response rate and missing data for questions, which may be due to electronic data collection errors or respondent choice. Recent ASH guidelines endorsed by the Children's Oncology Group propose limited general guidelines and do not consider a cancer patient's unique VTE risk profile. Given the variation seen, multi-center, prospective clinical trials are urgently needed for developing consensus guidelines for the management of VTE in children with leukemia. Figure 1 Disclosures Cooley: off-label: Other: drug use. Acharya:Takeda: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Anticoagulations that will be discussed are off-label in children.