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Background: After two years of COVID in which activities were reduced due to the pandemic and each one's life was affected by restrictions and limitations, the Sickle Cell Disease (SCD) Association in Padova teamed up with the Sickle Cell Group at the Pediatric Hematology Oncology and Bone Marrow Transplant Unit to celebrate the Sickle Cell Disease world day by organizing an online meeting with children/youths and their families. Theme of the meeting was: "My Life with SCD: poems, pictures and writings express our view on disease and care". Aim(s): One of the goals of this meeting was to create an opportunity for individuals with SCD to meet and have a constructive discussion with each other about the disease and express their feelings after two years of pandemic. Method(s): One month before the meeting children, teenager and parents were asked to sharer with the organizing team any drawing, painting, poem, writing, that they felt could express their feelings or experience of the disease itself or how it affected their life, or their experience in the hospital. The materials received were organized in a power point presentation and At the meeting, families were able to see a PowerPoint presentation with the poems, drawings, writings. Each author had the choice to personally share their production or have it read out loud by a member of the team. Free time to comment or share experiences was given. Result(s): 20 children, teenagers and parents participated. Countries of origin (Nigeria, Ghana, Congo, Albania, Italy), religious background (catholic, muslim, no religion, other) were different as well as disease genotype (HbSS, HbSC, HbSBdegree), severity or treatment received (Hydroxyurea, transfusion, Hematopoietic stem cell transplantation -HSCT, none). Drawings and writings regarded experience with the disease (mechanism of action, admissions), feelings experienced (fear, hope, light at the end of the tunnel), aspirations (sports) and gratitude (to the social and medical team, to parents) (Figure 1). Surprisingly, families who had a child having undergone HSCT, reported on the need and importance to talk about this experience for years after the event and made a request of a support goup. Finally, all families underlined the need to meet again soon to discuss together issues related to personal experience with SCD, even via web. of discussion with each other and with the drepanocytosis group;and that throug the online telematics platform it is still possible to involve all families, listening and trying to comfort them on doubts and perplexities about the disease, In conclusion, it can be said that after two years of pandemic, in our setting, online meeting can help patients and families reconnect with each other and activities can be planned to aid experiences and feelings. Patients' associations and Health Care Teams can collaborate in this area.
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Early in the COVID-19 pandemic, medical care providers at an acute illness hospital received increasing numbers of post-acute advanced COVID-19 patients from referring hospitals where they were showing no signs of improvement after receiving treatments from standard Emergency Use Authorization (EUA)-type protocols. The care providers turned to repurposing medications to treat these patients and added hydroxyurea, a medication commonly used for treating sickle cell anemia, to the hospital's COVID-19 treatment protocol and began to see notable clinical improvements. As the pandemic continued and new concerns arose concerning COVID-19 complications, those same care providers again turned to repurposing drugs. Focusing on the neuromuscular effects seen in COVID-19 patients, care providers turned to medications used to treat chronic neuromuscular conditions. Post-acute advanced Covid-19 patients initially received an abbreviated course of hydroxyurea followed by titrated doses of pyridostigmine. Positive responses were noted with cognition, diminished oxygen demands, progressive decrease in ventilator support, improved swallowing, and mobility. The authors suggest repurposed drugs could have great utility for treating COVID-19. It is recommended larger, COVID-19 clinical trials be completed to include hydroxyurea and pyridostigmine for validating the outcomes and clinical observations seen in these presented cases.
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Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and hypercoagulability disorders, several international agencies have included individuals with this disease in the COVID-19 risk group for severe outcomes. However, available information about the subject is not properly systematized yet. This review aimed to understand and summarize the scientific knowledge about the impact of SARS-CoV-2 infection in patients with sickle cell disease. Searches were performed in the Medline, PubMed, and Virtual Health Library databases based on descriptors chosen according to the Medical Subject Headings. We analyzed studies published between 2020 and October 2022, developed with qualitative, quantitative, or mixed methodology, and written in English, Spanish, or Portuguese. The search resulted in 90 articles organized into six categories. There is disagreement in the literature about how different aspects related to sickle cell disease, such as chronic inflammation status, hypercoagulability, hemolytic anemia, use of hydroxyurea, and access to medical care interference with the clinical course of COVID-19. These topics deserve further investigation. It is evident, however, that the infection may manifest in an atypical way and act as a trigger for the development of sickle cell-specific complications, such as acute chest syndrome and vaso-occlusive crises, conditions that are associated with great morbidity and mortality. Therefore, healthcare professionals must be aware of the different forms of presentation of COVID-19 among these individuals. Specific guidelines and therapeutic protocols, as well as public policies for sickle cell individuals, must be considered. Systematic review registration: This review (https://doi.org/10.17605/OSF.IO/NH4AS) and the review protocol (https://osf.io/3y649/) are registered in the Open Science Framework platform.
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Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.
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Transcranial Doppler (TCD) ultrasonography is a non-invasive ultrasound technique that uses high-frequency sound waves to measure blood flow velocities in the cerebral vasculature. This review analyzes TCD research in the Caribbean region using a bibliometric analysis of 29 articles from PubMed. The articles were analyzed using Microsoft Excel 2016 and the VOSviewer software (Van Eck and Waltman, Leiden University, Centre for Science and Technology Studies (CWTS), www.vosviewer.com) and characterized various aspects of TCD research, including countries, research themes, authorship, journals, affiliations, and keywords. The majority of the 29 publications came from Cuba (38%), followed by the French West Indies (22%) and Jamaica (20%). Most TCD research focused on sickle cell disease (SCD), accounting for 45% of the studies, followed by 21% of articles on vasospasm and subarachnoid hemorrhage. The use of TCD in brain death and neuro-intensive care was also explored, constituting 17% of the studies. Alternative TCD-monitored treatment options for SCD, such as stem cell transplantation and hydroxyurea, were also frequently investigated. The most productive institutions were Hospital Clínico-Quirúrgico Hermanos Ameijeiras in Havana, Cuba, the Sickle Cell Unit at the University of West Indies (UWI) Mona in Jamaica, the Medical-Surgical Research Center (CIMEQ) in Havana, Cuba, and the SCD Reference Center in Guadeloupe and Martinique in the French West Indies. TCD has been identified as a cost-effective tool for real-time monitoring of cerebral blood flow in many clinical settings, including stroke and SCD, which are prevalent in the Caribbean. Although there is an increase in the trend of using TCD for neuromonitoring in the Caribbean, gaps still exist. Capacity-building initiatives, such as training programs for healthcare providers and the development of local TCD research networks, can improve access to TCD in resource-constrained settings to treat and neuromonitor patients cost-effectively.
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Periorbital swelling is a clinical presentation with a broad differential and potentially deleterious consequence. Causes range from benign, including allergic reaction, to vision-and life-threatening, including orbital cellulitis and orbital infarction. The recent climate of SARS-CoV-2 has further complicated this differential, as the virus poses broad clinical presentations with new manifestations reported frequently. Rapid identification of the underlying etiology is crucial, as treatment approaches diverge greatly. Here, we report the case of an African American adolescent male with a history of homozygous sickle cell anemia presenting to an inner city hospital with bilateral periorbital swelling amid the coronavirus pandemic. Differentials including orbital cellulitis, COVID-MIS-C, orbital inflammatory syndrome, Hoagland sign, and orbital infarction secondary to sickle cell crisis are contrasted. We contrast our case with 12 case reports of orbital infarction in the setting of sickle cell crisis within the past 10 years, highlighting how these presentations, along with commonly reported findings of orbital infarction, compare with our patient. Copyright © 2022 Tehran University of Medical Sciences.
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Introduction: First synthesized in 1869, Hydroxyurea is known for its efficacy in treating myeloproliferative disorders, cervical cancer, and sickle cell disease. Usually well-tolerated, Hydroxyurea has numerous documented adverse effects, including bone marrow suppression, fevers, gastrointestinal upset, anorexia, and maculopapular rash. In addition, one rare side effect is interstitial pneumonitis, a potentially devastating complication if overlooked. We present one such case of Hydroxyurea-induced interstitial pneumonitis. Case Description: A 65-year-old man with a six-month diagnosis of Chronic Granulocytic Leukemia (CGL) on Hydroxyurea developed acute hypoxemic respiratory failure saturating 80% on room air with HR 102, RR 24, and increasing oxygen requirements (10 Lpm) after being admitted with complaints of worsening dyspnea, fatigue, and productive cough with yellow/green sputum. Physical examination was notable for cachexia, ill appearance, generalized weakness, hoarse voice, tachycardia, tachypnea, diffusely diminished breath sounds, and scattered rales on auscultation of lung fields. Initial imaging was notable for bilateral airspace disease and pulmonary opacities on chest radiography and bilateral pneumonia (concerning for COVID-19 pneumonia), mediastinal adenopathy, and splenomegaly on chest computed tomography. Initial laboratory results were notable for leukocytosis 62.5 th/uL, lactic acidosis 2.5 mmol/L, procalcitonin level 4.95 ng/mL, and negative COVID-19 PCR test. Prompt initiation of Vancomycin/Cefepime therapy ensued upon collection of blood cultures in light of possible sepsis. Flagyl, Valacyclovir, and Posaconazole were added to antimicrobial coverage, along with steroid therapy, due to minimal clinical improvement. Tachycardia with significant oxygen requirements alternating between BiPAP and heated high flow nasal cannula with FiO2 ranging from 70-85% persisted. Daily imaging also showed worsening airspace disease. Negative viral, bacterial, and fungal cultures led to subsequent discontinuation of Hydroxyurea therapy due to suspicion of medicationinduced pneumonitis. Three days after cessation of Hydroxyurea, the patient's oxygen requirements began to decrease and imaging revealed interval resolution of pneumonitic changes in the absence of antimicrobial therapy. The patient was later transitioned to Ruxolitinib for his underlying CGL prior to his discharge home without the need for home oxygen therapy. Discussion: Thought to be caused by hypersensitivity pneumonitis, pulmonary toxicity from Hydroxyurea can easily be misdiagnosed. Unfortunately, while much is known about the pancytopenic, gastrointestinal, and cutaneous side effects of Hydroxyurea, few cases in the literature highlight the potentially fatal interstitial pneumopathy caused by Hydroxyurea, first reported in 1999. Thus, this case serves as an additional contribution to the minutiae of literature detailing Hydroxyurea's adverse pulmonary side effect profile. (Figure Presented).
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Background: Therapeutic options for Sickle Cell Disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. Objectives: To assess the clinical practice patterns of providers treating children with SCD. Design/Method: A survey study was performed which included nine sections: clinic structure, prophylaxis, immunizations, hydroxyurea, splenic sequestration, stroke, novel therapies, potential curative therapies, and transition. Survey was disseminated over a three-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology-Oncology Hemoglobinopathy Special Interest Group. Results: There were 86 respondents;most were attending/faculty (85%, 73/86) who were part of a university/academic practice (65%, 56/86). Program size was most commonly 50-250 patients (44%, 37/86). Accessibility to support staff in clinic included 95% (81/86) social work;76% (65/86) child life;68% (58/86) nurse coordinator and 34% (29/86) school liaison and 15% (13/86) transition navigator. For preventive care, 72% prescribe penicillin prophylaxis before 2 months of age recommending 100% (83) for HbSS and Sβnull, 72% (60/83) for HbSC and 70% (58/83) for HbSβplus. Influenza was the most common vaccine offered in clinic at 96% (76/79) with 91% (72/79) offering pneumococcal vaccines, 84% (67/79) offering meningococcal vaccines and 50% (40/79) offering COVID vaccines. Transcranial doppler screening was offered in 95% (69/73) but only 42% (31/73) performed MRI screening for silent stroke. Transfusion therapy was recommended for primary stroke prevention by 90% (65/72) and 84% (59/70) attempt to transition to hydroxyurea following TWITCH guidelines. For secondary stroke prevention, 88% (63/72) recommend chronic transfusion therapy. Regarding disease-modifying therapy, 90% (70/78) report starting hydroxyurea routinely in patients with HbSS and Sβnull;initiated at 9 months of age by 69% (54/78). Laboratory monitoring recommended every 3 months for stable dosing by 62% (49/78) and hydroxyurea held by 56% (44/78) if platelets <75,000, 73% (56/78) for neutrophils <1000. New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68% (37/54;crizanlizumab 93% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin 65% (43/66). Matched sibling transplant was considered for any disease severity by 55% (38/69). Gene therapy trial is offered on-site by 29% (20/69). Transition programs were endorsed by 61% (42/69), but only 45% (31/68) had dedicated staff. Conclusion: This survey is the only assessment of the application of SCD guidelines in clinical practice.
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Aim Develop the hydroxycarbamide prescribing process for sickle cell disease to improve outcomes and patient experience through: implementing electronic prescribing;identifying and addressing non-adherence;optimising doses;improving accessibility of medication and developing a hydroxycarbamide telephone clinic. Method The clinic was planned to be piloted mid-2020 however due to the COVID pandemic requiring more services to be delivered remotely the timeline was accelerated and all patients switched to telephone reviews in March 2020. New patients are commenced on hydroxycarbamide at a face-to-face outpatient appointment which includes counselling and consent, review of baseline bloods, introduction to the telephone clinic and medication counselling. Patients are then eligible for the hydroxycarbamide telephone clinic. Patients attend outpatient phlebotomy for the necessary monitoring blood tests prior to their telephone appointment. At the telephone appointment a virtual review takes place including a review of symptoms, blood results, medication adherence and adverse effects. An 8-12 week supply of hydroxycarbamide is prescribed by a nurse or pharmacist prescriber and sent to the patient's local pharmacy or home address by the hospital outsourced pharmacy. Follow up appointments are made every 8-12 weeks. Patients continue to have face to face medical appointments;the interval is determined by individual patient factors but a minimum of annually. Results In September 2019 (prior to electronic prescribing) an audit of patients who had been on hydroxycarbamide for 9 months or more (n=26) had a mean dose of 21.7mg/kg. A repeat audit in July 2021 showed a mean dose of 26.9mg/kg (n=36). Electronic prescribing has facilitated more accurate prescription records and structured dose escalation. It also supports better monitoring of adherence since it is clear during a review when the next supply should be required. This along with questioning what medication supply patients have at home allows adherence issues to be identified and discussed with patients/carers. An audit of haematology outpatient clinic waiting times prior to implementation showed an average wait time of 82 minutes;one of the recommendations was to implement this telephone clinic. In a patient/carer survey on care during the pandemic, 88% of respondents were happy with the telephone reviews they had received and 82% wished to continue with telephone clinics. Conclusion The results show an escalation in hydroxycarbamide dose which correlates with a higher fetal haemoglobin, this in turn is associated with increased survival.1. This has been facilitated by the increased opportunity to focus on prescribing and medication review. From March 2020 to May 2021, due to the pandemic, dose escalation only took place if patients were admitted with crisis so further improvement may be seen in the future.
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CPX-351 (Vyxeos® liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine at a synergistic 1:5 molar drug ratio. Since 2018, NICE has recommended CPX-351 for the treatment of newly diagnosed, therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC) based on results from a pivotal phase 3 trial of older adults. After 5 years of follow-up in the phase 3 trial, CPX-351 induction followed by consolidation improved median overall survival (OS) versus a 7+3 regimen of cytarabine and daunorubicin, with a comparable safety profile. Patients with AML in the United Kingdom have been treated in two key National Cancer Research Institute (NCRI) clinical trials (AML-18 and AML-19) that are exploring the role of CPX-351 outside of its licensed indications. Prospective interventional trials provide important clinical data but are often conducted in restricted populations that may not reflect the overall licensed population. Real-world analyses complement prospective trials by providing regional data on treatment outcomes and healthcare resource utilisation in everyday clinical practice, as well as by addressing data gaps, thus allowing clinicians to assess drug performance more fully. Additionally, with the approval of multiple novel agents for AML in the past few years and the complexities of treating AML during the COVID-19 pandemic, localised datasets that build on drug risk-benefit profiles are important for informing treatment decisions. Real-world outcomes of CPX-351 have recently been published for French, Italian and German cohorts, making this study (CREST) on treatment outcomes with CPX-351 in the United Kingdom essential from a national perspective. CREST ( C PX-351 R eal-world E ffectiveness and S afe t y Study;ClinicalTrials.gov NCT05169307) is a retrospective, non-interventional, multicentre, single-arm, observational study designed to collate efficacy and safety data for patients treated with CPX-351 according to its licensed dosage regimen in the United Kingdom. Data from approximately 150 patients treated since 2018 at 10 to 15 centres will be collected. Patients aged ≥18 years, diagnosed with t-AML or AML-MRC, and treated with ≥1 infusion of CPX-351 are eligible for the study. Patients previously treated in a clinical trial or who have received ≥1 induction treatment with another antineoplastic agent (except hydroxyurea) after their AML diagnosis will be excluded. The primary objectives of the study include assessment of remission rates (including measurable residual disease assessment) and OS. Secondary objectives include the collection of data related to patient characteristics, cytogenetic and molecular genetic features of AML, dosing schedule of CPX-351, potential prognostic factors for remission and OS outcomes, haematopoietic cell transplant rates and post-transplant outcomes, and safety. The study will also report on outpatient/ambulatory delivery of CPX-351, a shift away from conventional inpatient delivery of intensive chemotherapy, and its impact on cumulative resource utilisation. An exploratory analysis of the clinical presentation, management and outcomes of patients infected with COVID-19 who were treated with CPX-351 will also be included in the study. It is hoped the study will provide much-needed UK data to guide clinicians in the treatment of patients with t-AML or AML-MRC. Study sites are currently being recruited, with data collection expected through the first half of 2022..
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Pegylated Interferon (PegIFN) is the recommended first-line cytoreductive therapy in patients aged <40 years with essential thrombocythaemia (ET) or polycythaemia vera (PV). However, its use in patients >60 years is often limited due to concerns about tolerability. In this study, we evaluate the efficacy and tolerability of PegIFN in patients >60 years at University College London Hospitals (UCLH). Using electronic medical records, we identified patients with ET, PV or myelofibrosis at UCLH who commenced treatment with PegIFN between 2010 and 2020 and were aged >60 years on starting therapy. Data were collected until April 2021 to allow a minimum of 1-year follow-up. Complete Haematological responses were defined as per standard European Leukaemia Net criteria. Adverse events (AE) were graded 1-5 according to Common Terminology Criteria for Adverse Events (CTCAE). Thrombosis risk was graded according to IPSET criteria for ET patients. Patients with PV were classed as high risk if they were aged >65 or had a previous history of thrombosis. Eighteen patients were included in the study. The median age was 75.1 years (range 63-91), 61% were female. Ten out of 18 (56%) had a diagnosis of ET, seven out of 18 (39%) of PV and 1/18 (6%) of post-ET myelofibrosis. Fifteen out of 18 (83%) were positive for JAK2 V617F, and two out of 18 (17%) were positive for CALR mutation. Ten out of 18 (56%) had significant cardiovascular co-morbidities at diagnosis. Five out of 18 (28%) had arterial or venous thromboembolic disease at diagnosis. Sixteen out of 18 (89%) were high-risk for thromboembolic events at diagnosis. Seventeen (94%) patients had PegIFN as a second-or thirdline agent. Of these, 15 out of 17 had received hydroxycarbamide (HU) as first-line therapy;two out of 17 had interferon alpha. PegIFN was started at a median age of 70 years (range 50-86) and continued for 5.7 years (range 2-13). Twelve out of 18 (67%) patients achieved complete remission (CR) on PegIFN monotherapy;1 out of 18 (6%) achieved CR on PegIFN and HU combination therapy, and the remaining 5 out of 18 (28%) achieved a partial remission (PR). The median time to CR was 5 months (range 1-40 months). Ten out of 18 (56%) had grade 1-2 AEs including skin rashes, cytopenia and fatigue. Three out of 18 (17%) developed a major thromboembolic event while on treatment (brachial artery embolism, transient ischaemic attack and a non-ST elevation myocardial infarction). Of these, two out of three failed to achieve a CR on PegIFN and required ongoing venesection. The third had suboptimal response due to dose escalation limited by grade 3 neutropenia. Thirteen patients (72%) remained on pegIFN at the end of the study period. Of those who discontinued, three out of five stopped due to cytopenias, one out of five died during the study period of Covid-19 infection and one out of five transformed to myelodysplastic syndrome. In this study, we present a group of patients who were at high risk for thrombosis due to their age and cardiovascular risk factors. The majority of AEs documented were grade 1-2, with only three out of 18 (17%) patients discontinuing due to AEs. The rate of CR 72% similar to that quoted in imminent studies including MPN-RC (Knudsen et al, 2018) and DALIAH trials (Mascarenhas et al, 2018), which recruited larger numbers of youngers ET and PV patients on PegIFN. Over 20% of MPN patients develop resistance or intolerance to HU (Sever et al, 2014);therefore, there is a need for alternative cytoreductive agents. Our study demonstrates PegIFN to be effective and well-tolerated for use in patients >60 years and is an excellent cytoreductive option in this cohort.
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Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) and one of the leading causes of mortality in SCD patients. The management of ACS is challenging and requires prompt intervention to halt clinical deterioration. With the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, which also primarily results in acute respiratory illness, the clinical picture and treatment outcome in SCD patients with ACS remain unknown. We present a case of a 30-year-old male who came in with features of painful vaso-occlusive episode and haemolysis that later evolved to acute chest syndrome. Chest X-ray showed pneumonic changes and mild bilateral pleural effusion, and nasal Reverse Transcription-Polymerase Chain Reaction (RT-PCR) for COVID-19 test came out positive. He was managed supportively with simple transfusion, antibiotics, dexamethasone and oxygen support with a good clinical outcome. Presenting with non-specific symptoms and similar respiratory symptoms and signs, the clinical picture of COVID-19 can prove difficult to discern from that of ACS due to other causes. This report emphasizes a need for a higher index of suspicion whenever a SCD patient presents with symptoms of acute respiratory distress.
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Background: Patients with hematologic conditions have a high mortality rate when infected with SARS-CoV-2 (Williamson, Nature 2020). Protection of this group from severe COVID-19 is therefore important. However, according to available vaccination guidelines, one should consider to postpone vaccination of patients on or early after chemotherapy, hematopoietic progenitor cell transplantation (HCT) or with graft versus host disease, because of anticipated poor efficacy. Based on previous (non-COVID-19) vaccination studies among hematology patients, we hypothesized that a significant group of patients may acquire sufficient protection following COVID-19 vaccination, despite disease and therapy related immunodeficiencies. Methods: We conducted a prospective cohort study with 17 cohorts of hematology patients of particular risk for severe COVID-19 who are considered to have no or limited benefit from vaccination. We evaluated humoral immune responses following 2 doses (28 days apart) of the mRNA-1273 vaccine (Moderna/Spikevax) in 722 patients, at baseline and 28 days after each vaccination as SARS-COV-2 S1- (spike)-specific serum IgG antibody concentrations by bead-based multiplex immune assay. The threshold for adequate antibody response is set at ≥300 binding antibody units (BAU)/ml according to the international WHO standard, and is associated with virus plaque reducing neutralization test titers of ≥40 PRNT 50. This study is registered as EudraCT 2021-001072-41, NL76768.029.21. Results: Patient cohorts and corresponding vaccine responses are depicted in Table 1. Vaccine efficacy, as measured by antibody concentration, 4 weeks after the 2nd mRNA-1273 vaccination was available for 691 out of 722 participants. The majority of patients (389/691;56%) obtained an S1 antibody titer that is considered adequate (≥300 BAU/ml). Twenty-nine percent of patients (198/691) did not seroconvert (S1 antibody titer <10 BAU/ml), while the remaining 15% (104/691) did seroconvert but not to sufficient levels (10-300 BAU/ml). Adequate responses were observed in the majority of patients with sickle cell disease using hydroxyurea, chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor therapy, acute myeloid leukemia (AML) on or early after high dose chemotherapy, patients with myeloproliferative disorders on ruxolitinib, patients with multiple myeloma (MM), including those on daratumumab and those early after high-dose melphalan and autologous HCT, patients with untreated chronic lymphocytic leukemia (CLL), and patients with chronic GvHD. Insufficient or absent antibody responses were observed in the majority of AML patients receiving hypomethylating agents, CLL patients on ibrutinib, patients with B-cell non-Hodgkin's Lymphoma (NHL) during or shortly after rituximab-chemotherapy or following BEAM chemotherapy and autologous HCT, allogeneic HCT recipients <6 months after transplantation, and CAR-T cell therapy recipients. However, even in these low-responder groups considerable numbers of patients did mount sufficient antibody titers. In others, titers increased after each of both vaccinations, suggesting that booster vaccination may enhance antibody titers to sufficient levels (Figure 1). Conclusion: Vaccination with mRNA-1273 had significant efficacy in severely immunocompromised hematology patients. Adequate humoral immune responses after two dose vaccination were reached in the majority of patients receiving therapy for sickle cell disease, MPD, MM, CML and AML, in patients early after HCT and in patients with GvHD. We are currently evaluating clinical and immunologic parameters that correlate with sufficient antibody responses, pseudovirus neutralization and SARS-COV-2-specific B and T cell numbers, phenotype and function. Per study design, all participants with absent or insufficient antibody responses (<300 BAU/ml) will receive a booster vaccination 5 months after initial vaccination, and antibody responses to booster vaccinations will be presented as well. Unlike currently available guidelines, COVID-19 vaccination should not be postponed. Moreover, as antibody titers increased after each of both vaccinations, booster vaccination of patients with absent or insufficient antibody responses seems warranted. (Figure Presented) .
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Background The iCMLf CANDID study represents the largest global cohort study to date characterizing COVID-19 in CML. This real world data collection, from 157 institutions in 49 countries, is essential to differentiate impact of patient, disease, and therapy specific factors on risk and outcomes, as the pandemic continues. Objective The primary aim of the CANDID study is to collect and analyze information on COVID-19 cases among CML patients (pts) to define risk factors, clinical evolution and outcome. Patients and methods Since March 2020, the iCMLf has collected data, with contributions from physicians treating CML pts and partner organizations. Country income was determined according to the World Bank Data. COVID-19 severity was classified according to the World Health Organization criteria. Univariate analysis was performed using log-rank test or logistic regression. Multivariate analysis was performed using Cox proportional hazards model or multivariate logistic regression. All the statistical analysis was performed using R statistical software (version 4.0.2). Results By April 2021, 642 cases of COVID-19 were reported from 50 countries. COVID-19 was diagnosed by PCR and/or serology in 601 pts (94%) and clinically suspected in 41 pts (6%). These 642 pts were reported by 186 physicians managing an estimated 37,449 CML pts (approximate incidence 0.7%). Most cases reported were from Europe (52%), followed by Asia (18%) and South America (16%). North America reported 10% of the cases and Africa 2.8%. The median age at the time of COVID-19 diagnosis was 53 years (18-94) and 59% of pts were males. Median time from CML diagnosis to COVID-19 was 8.34 years (range: 0-34). CML treatment at the time of COVID-19 diagnosis: hydroxyurea in 4 pts (6%), 38 (6%) bosutinib, 96 (15%) dasatinib, 275 (43%) imatinib, 92 (14%) nilotinib, 18 (3%) ponatinib, 3 (0.5%) other 4th generation TKIs;one alpha interferon. Ninety-nine (15%) pts were not receiving any treatment: 53 (8%) were in treatment free-remission (TFR) and 46 were without treatment (7%) for other reasons: treatment side effects (7), stem cell transplantation (12), pregnancy (3), lack of efficacy (2), unknown (1) and newly diagnosed CML (21). Significant comorbidities were present in 281 pts (44%), most common were: heart conditions, including hypertension (162), diabetes (76), lung diseases (47) obesity (42) and others (84). COVID-19 was asymptomatic in 53 cases (8%), mild in 363 cases (56%), moderate in 119 cases (18%), severe/critical in 86 cases (13%) and of unknown severity in 21 cases (3%). At the data cut-off, from the 606 pts with known outcome, 48 pts died (8%) and 558 (92%) recovered. Age >75y (Fig 1A, p<0.001), comorbidities (Fig 1B, p=0.039), low income country (Fig 1C, p<0.001), advanced phase CML at time of COVID-19 (Fig 1D, p<0.001) had statistically significant association with overall survival (OS) in CML pts with COVID-19. OS was 71% in low or lower middle income countries, 93% in upper middle and 95% in high-income countries (Fig 1C, p<0.001). The mortality rate for pts with cardiovascular disease;heart failure, coronary artery disease, cardiomyopathies, hypertension, stroke or cerebrovascular disease (12%), and chronic lung disease (13%) were higher than those pts with other comorbidities (6%), or without comorbidities (4%;p=0.003;Fig 1E). By multivariate analysis, all these risk factors remained significantly associated with OS. For pts who were hospitalized with severe disease, age >75y (p=0.037), comorbidities (p=0.001), male gender (p=0.01), CML status (AP/BC vs CP in MMR;p=0.049), CML treatment (pre-TKI vs TFR;p=0.02) and length of time with CML (p<0.05) were significant risk factors for mortality. By multivariate analysis, all the risk factors except age remained significant. The risk factors for mortality for pts with moderate, severe, or critical disease were age >75y (p=0.003) and low and lower middle income countries (p<0.001), both confirmed by multivariate analysis. Conclusions We confirmed a higher mortality for CML pts with COVID-19 n older pts (>75y), pts with cardiovascular or pulmonary comorbidities and from low and low-middle income countries, the latter probably related to limitations in supportive care. Additionally, more deaths occurred in pts in advanced phases and in pts not in MMR.
ABSTRACT
Curvularia species are dematiaceous filamentous fungi that can cause a variety of infections in both immunocompetent and immunocompromised hosts. We present 2 cases of severely immunosuppressed patients with acute invasive fungal sinusitis due to Curvularia species. Both patients had a history of hematologic malignancy with refractory disease and prolonged neutropenia. They presented with facial and sinus pain, which prompted maxillofacial computed tomography that showed acute sinusitis. Subsequently, they underwent nasal endoscopy with a biopsy that revealed a definitive diagnosis of invasive fungal sinusitis. Dematiaceous fungi are responsible for most fungal sinusitis cases, with Curvularia being one of the most common species isolated. Generally, invasive fungal rhinosinusitis may follow a relatively innocuous and nonspecific course. In addition, fungal infections may complicate chronic allergic sinusitis. Computed tomography scan is the first imaging modality of choice, and magnetic resonance imaging has a role in prognostication in acute invasive fungal rhinosinusitis. Endoscopic sinus surgery with biopsy yields a definitive diagnosis and is therapeutic. Management typically includes a combination of surgery and antifungal agents. Severe neutropenia is a significant risk factor for infection and is associated with poor outcomes. Aggressive surgical debridement, combined with antifungal therapy, should be emphasized in leukemic patients despite their prolonged neutropenia and bleeding tendency.
ABSTRACT
INTRODUCTION: Patients (pts) with blood disorders are at particular risk for severe infection and death from COVID-19. Factors that contribute to this risk, including cancer treatment, have not been clearly delineated. The ASH RC COVID-19 Registry for Hematology is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in pts with underlying blood disorders. We report a multivariable analysis of the impact of cancer treatment and other key variables on COVID-19 mortality and hospitalization among pts with blood cancer. METHODS: Data were collected between April 1, 2020, and July 2, 2021. All analyses were performed using R version 4.0.2. Multivariable logistic regression explored associations between mortality and seven patient/disease factors previously reported as important to COVID-19 outcome. Independent variables included: age (>60);sex;presence of a major comorbidity (defined as any of heart disease, hypertension, pulmonary disease and/or diabetes);type of hematologic malignancy;estimated prognosis of < 6 months prior to COVID-19;deferral of ICU care;and administration of cancer treatment in the previous year (excluding single agent hydroxyurea). A secondary multivariable logistic regression explored associations between the same variables and hospitalization with COVID-19. RESULTS: We included all pts in the registry with a malignant diagnosis except for 3 patients excluded based on a data sharing agreement (N=1029). Median age category was 50-59y (range <5y to > 90y). The sample was 42% female and 28% had major comorbidities. Types of hematologic malignancies were 354 (34%) acute leukemia/MDS, 255 (25%) lymphoma, 206 (20%) plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) CLL, 98 (10%) myeloproliferative neoplasm (MPN). Most pts (73%) received cancer treatment during the previous year, 9% had a pre-COVID-19 prognosis of <6months, and 10% deferred ICU care. COVID-19 mortality in the entire cohort was 17%. In multivariable analyses, age > 60 (OR 2.03, 1.31-3.18), male sex (OR 1.69, 1.11 - 2.61), estimated pre-COVID-19 prognosis of less than 6 months (OR 6.16, 3.26 - 11.70) and ICU deferral (OR 10.87, 6.36 - 18.96) were all independently associated with an increased risk of death. Receiving cancer treatment in the year prior to COVID-19 diagnosis and type of hematologic malignancy were not significantly associated with death. In multivariable analyses, age > 60 (OR 2.46, 1.83 - 3.31), male sex (OR 1.34, 1.02 - 1.76), estimated pre-COVID-19 prognosis of < 6 months (OR 4.81, 2.45 - 10.50), presence of a major comorbidity (OR 1.57, 1.15 - 2.16), and cancer treatment in the previous year (OR 1.50, 1.10 - 2.06) were all independently associated with an increased risk of a severe COVID-19 requiring hospitalization. Pts with a MPN or plasma cell dyscrasia and COVID-19 were less likely to require hospitalization for COVID-19 compared to patients with CLL, leukemia/MDS, or lymphoma. CONCLUSIONS: These analyses confirm the negative impact of age > 60, male sex, pre-COVID-19 prognosis of < 6 months, and deferral of ICU care on mortality among patients with hematologic malignancy and COVID-19. We did not observe an increased risk of COVID-19 mortality among pts with COVID-19 who received blood cancer treatment in the previous year, although rate of hospitalization was higher. Pts with some hematologic malignancies (MPN, plasma cell dyscrasias), may experience less severe COVID-19 infections than others. Disclosures: Anderson: Celgene: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Desai: Janssen R&D: Research Funding;Astex: Research Funding;Kura Oncology: Consultancy;Agios: Consultancy;Bristol Myers Squibb: Consultancy;Takeda: Consultancy. Goldberg: Celularity: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Aptose: Consultancy, Research Funding;Prelude Therapeutics: Research Funding;DAVA Oncology: Honoraria;Pfizer: Research Funding;Arog: Research Funding;Aprea: Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership;Pharmacyclics: Research Funding. Radhakrishnan: Janssen India: Honoraria;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Aurigene: Speakers Bureau;Novartis: Honoraria;Johnson and Johnson: Honoraria;Pfizer: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria;Emcure Pharmaceuticals: Other: payment to institute;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;NATCO Pharmaceuticals: Research Funding. Sehn: Genmab: Consultancy;Debiopharm: Consultancy;Novartis: Consultancy. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees;Syros: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;NYU Grand Rounds: Honoraria;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria.
ABSTRACT
Background: Persons with Sickle Cell Disease (SCD) infected with the SARS CoV-2 virus have significantly increased risks of hospitalization and death and are strongly recommended to be fully vaccinated. Vaccine hesitancy has previously been described in the SCD population and uptake of other recommended vaccines has been reported to be low in some studies. The goal of this study was to assess how vaccination rates amongst eligible pediatric and adult SCD patients in British Columbia (BC), Canada, compared to those of the general population and other “clinically extremely vulnerable” (CEV) groups. Methods: Persons age 12 and over with SCD in BC were identified as a CEV population and prioritized for immunization. A comprehensive process was undertaken to find and identify all CEV patients in BC and notify them of their priority status. Individuals diagnosed with SCD in the province were identified in the shared pediatric and adult patient registry (iCHIP), which tracks demographics, diagnoses and therapies, and added to the CEV patient list. SCD patients were notified of their priority status through standard mail from the provincial health officer, as well as emails and phone calls from the pediatric and adult SCD programs. Those aged 16+ were invited to register for immunization beginning in March 2021 while those 12-15 years were permitted to register starting in May 2021. Adult patients were eligible to receive mRNA vaccines from Pfizer and Moderna as well as the Astra-Zeneca (AZ) COVISHIELD vaccine, while those aged 12-17 were eligible only for Pfizer vaccines. The provincial immunization registry (PIR) was interrogated to confirm vaccine administration. The main outcome measure was the proportion of SCD patients who received 1st and 2nd dose COVID vaccines. Results: 138 individuals age 12+ with SCD were identified in the iCHIP database. 71.0% had Sickle Cell Anemia (SCA), 25.4% had Hemoglobin SC (Hb SC) and 3.6% had other genotypes. Participants ranged in age from 12-69 years with a median of 28 years. 67.4% were receiving disease-modifying therapy (76 were on hydroxyurea, 11 on regular red cell exchange, 1 was receiving crizanlizumab, and 5 with Hb SC were phlebotomized). None were treated with gene therapy or transplant. 7 individuals had a PCR-confirmed SARS CoV-2 infection prior, but none following immunization. As of July 30, 2021: 68.8% of persons with SCD received a 1st and 55.1% received a 2nd dose of COVID vaccine. Almost all doses were mRNA-based vaccines with the exception of a single 1st dose administration of AZ. Vaccination rates amongst different age ranges and genotypes are displayed in Table 1. Patients with SCA did not have significantly different vaccination rates compared to those with Hb SC/other genotypes: 64.3% versus 80.0% for 1st dose (p=0.0703) and 48.0% versus 62.5% (p =0.12114) for 2nd dose. Vaccination rates amongst the SCD group were compared to other age matched CEV populations as well as the general provincial population and are detailed in Tables 2 and 3. A higher proportion of persons with SCD under the age of 20 received 1st dose (70.8% versus 31.1%;p<0.00001) and 2nd dose (50.0 versus 15.3%;p <0.00001) of vaccines compared to the general population. However, a lower proportion age 20-49 and 50+ years old received a 1st dose as demonstrated in Table 2. In addition, lower proportions of persons with SCD of all age ranges were vaccinated in comparison to other CEV groups. As demonstrated in Table 3, SCD was not associated with receiving a 1st dose vaccine compared to the general BC population (OR 0.8, 0.56 to 1.16 95% CI, p=0.2481). In contrast, persons in other CEV groups were twice as likely to receive a first dose COVID immunization compared to the general BC population (p<0.0001). No severe vaccine-related complications including vaccine-induced immune thrombotic thrombocytopenia (VITT) were reported. There were 7 presentations to hospital for vaso-occlusive crises (VOC) within 21 days of immunization. Conclusion: Despite an active CEV process to find and invite perso s with SCD to be vaccinated, these data demonstrate that vaccination rates amongst persons with SCD in BC are below those of other CEV age-matched groups. Vaccination rates amongst adults are also lower than the general population, however there is a high vaccination rate in persons under 20 years old. A subsequent qualitative study exploring COVID vaccine hesitancy amongst persons with SCD in BC is being explored. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
[Formula presented] Background: Sickle cell disease (SCD) is a chronic blood disorder, which disproportionately impacts Black individuals. Hydroxyurea therapy prevents SCD-related complications;yet it is underutilized, which contributes to further health inequities. Mobile health (mHealth) apps for patients and providers have the potential to improve hydroxyurea adherence. Our objective was to use the RE-AIM framework to evaluate the impact of the COVID-19 pandemic on implementation and effectiveness of patient and provider hydroxyurea (HU) mHealth apps (InCharge Health app and HU Toolbox app, respectively) in two large academic medical centers. Methods: Patient-level data (n=46) were collected between 11/2019-7/2020. Adherence was measured by calculating Percentage of Days Covered (PDC) from prescription records over 24 weeks before implementing the mHealth apps and during 12 and 24 weeks of implementation. As a response to the COVID-19 pandemic and to reduce virus spread, both sites temporarily suspended non-emergent clinical activities. During implementation, Site A clinics shut down for approximately 2 months (3/2020-5/2020) and Site B clinics for 7 months (3/2020-10/2020). To better understand contextual factors associated with mHealth implementation, we purposively sampled participants according to app use level (high vs low) and conducted semi-structured interviews with adult SCD patients, providers (physicians, nurse practitioners, and physician assistants), administrators, and research staff between 6/2020 and 3/2021. Results: A total of 46 patients participated and contributed to the PDC hydroxyurea adherence data. Mean change in PDC, adjusted for baseline PDC, was greater at Site A than at Site B (12-weeks: difference = 16.59%, p=.01, Figure 1A;24-weeks: difference = 15.08%, p=.01, Figure 1B). Eleven patients (mean age 26.2 years old, 64% males, 100% Black, 73% HbSS, 45% low app users) and 11 providers (mean age 36.7 years old, 73% females, 36% Black, 54.5% physicians, average 8 years in practice, 36% low app users) completed the semi-structured interviews across the 2 sites. Site B was more affected during the COVID-19 pandemic where patients had difficulty obtaining hydroxyurea and other challenges related to reaching their providers and clinic setting for non-urgent or emergent reasons. In addition, participants with lower baseline hydroxyurea adherence level, as measured by PDC, had a more remarkable improvement in their PDC values at 12 weeks (Figure 1C) and 24 weeks (Figure 1D) Additional qualitative data focused on the implementation process were collected from 3 administrators, and 4 research staff. Among patients, both high and low app users reported the pandemic was a barrier to getting needed care (e.g., difficulty getting to hospital/clinic) and obtaining hydroxyurea;this was particularly a concern among low app users at Site B. Among providers, all but 2 high app users reported the pandemic did not impact app use, but nearly all low users perceived the pandemic to be a barrier to using the provider app because fewer patients came to clinic for maintenance SCD visits during the COVID-19 pandemic. Low users also reported the pandemic would negatively impact continued use of the app. Administrators and research staff also said reduced in-person clinic visits were a barrier to app implementation. Conclusions: mHealth apps are promising tools for improving hydroxyurea adherence among adolescents and adults with SCD. Contextual data show that some patients who experienced challenges accessing healthcare during COVID-19 pandemic have also experienced challenges navigating mHealth implementation. A focus on removing barriers to mobile apps use during care disruptions will likely improve patient and provider mHealth apps implementation, and ultimately, reduce health inequities for this vulnerable population. Our findings suggest that strategies such as including an mHealth facilitator has the potential to help addressing some of these implementation challenges. Note: Sherif Badawy and Lisa DiMarti o are co-first authors with equal contribution [Formula presented] Disclosures: Badawy: Sanofi Genzyme: Consultancy;Bluebird Bio Inc: Consultancy;Vertex Pharmaceuticals Inc: Consultancy. Shah: Alexion: Speakers Bureau;Bluebird Bio: Consultancy;CSL Behring: Consultancy;Emmaus: Consultancy;GBT: Consultancy, Research Funding, Speakers Bureau;GLG: Consultancy;Guidepoint Global: Consultancy;Novartis: Research Funding, Speakers Bureau. Hankins: Bluebird Bio: Consultancy;UpToDate: Consultancy;Vindico Medical Education: Consultancy;Global Blood Therapeutics: Consultancy.
ABSTRACT
Introduction: In December 2019, a new variant of a coronavirus led to a pandemic outbreak. Patients with haematological malignancies are at high risk for a severe progression of COVID-19 with high mortality rates. Case report: 54-year-old patient was tested positive for COVID-19 upon admission. The CT scan showed bilateral ground-glass pulmonary opacities. He received dexamethasone and remdesivir. Due to severe thrombocytopenia and detection of blasts in peripheral blood a bone marrow biopsy was done. Cytological and molecular results confirmed the diagnosis intermediate risk APL. We started a therapy with arsenic trioxide and all-trans retinoic acid (ATO/ATRA). The white blood cells (WBC) increased and the respiratory situation worsened. The patient developed a thrombophlebitis. Bleeding complications appeared as an epistaxis, which required an intervention. 28 days after starting the induction, the bone marrow biopsy showed < 5% blasts. A complete peripheral remission was documented on day 50. Discussion: A major concern in treating APL is the differentiation syndrome, which can ultimately result in pulmonary failure. This patient presented with severely impaired lung function due to simultaneous COVID-19 pneumonitis. Therapy of APL had to consider both clinical conditions. Key decisions were (beyond antiviral therapy and supportive measures) a consequent dosing of glucocorticoids and early cytoreductive therapy using hydroxyurea (HU). The pulmonary function was critical during days 7-15 after start of APL therapy, consistent with differentiation syndrome being the main cause of worsening, and clinically met by stop of ATO/ATRA. Another concern was coagulation dysfunction, given the high risk of thromboembolic complications associated with COVID-19, the severe thrombocytopenia and plasmatic coagulation disorder caused by APL. In this case - besides supportive platelet transfusions - we treated by low dose heparin only when a thrombophlebitis occurred. Overall in this patient presenting with COVID-19 and simultaneously APL, the most challenging problem was overcoming pulmonary worsening in the initial phase of APL therapy.