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Introduction: Use of hematopoietic cell transplantation (HCT) in patients with trisomy 21 (+21) is infrequent given concerns about increased toxicity with cytotoxic chemotherapy.1 Due to increasing evidence of benefit from post-HCT cyclophosphamide (PTCy) for graft-vs.-host disease (GVHD) prophylaxis and lack of prior descriptions in patients with +21,2-4 we report on 2 patients with +21 and acute lymphoblastic leukemia (ALL) who underwent HCT with PTCy. Method(s): Retrospective data were collected from 2 patients with ALL and +21 who underwent allogeneic HCT with PTCybased GVHD prophylaxis from 2019 to 2021. Data collected included age, disease risk, HCT-CI, GVHD incidence, and survival. Result(s): Patient 1 is a 22-year-old male and patient 2 a 25-year-old female. Both had Ph-negative, B-cell ALL. Patient 1 had ETV6/RUNX1 rearrangement, del 12p, gain of X, and he had recurrence of measurable residual disease (MRD) after initial MRD-negative CR with two lines of therapy pre-HCT. Patient 2 had normal cytogenetics and relapsed disease with 4 prior lines of therapy. Both achieved MRD-negativity pre-HCT. Both received fludarabine and melphalan conditioning, and patient 1 also received thiotepa 2.5 mg/kg. PTCy was given on days +3 and 4 at 50 mg/kg with sirolimus and tacrolimus for GVHD prophylaxis. Patient 1 had a haploidentical donor and received one dose of rabbit ATG (1 mg/kg) on day +5. Patient 2 had a matched unrelated donor. There was no significant delay in engraftment of ANC (day 16-19) or platelets (day 15-16). Patient 2 developed acute GVHD at day 30 (stage I skin, stage II GI) that resolved with steroids which were tapered off by day 96 without recurrence. Sirolimus stopped at day 79 (pt 1) and 103 (pt 2) and tacrolimus was stopped at day 274 (pt 1) and 469 (pt 2). Patient 1 developed a sirolimus-induced pericardial effusion at day 84 which did not recur after sirolimus discontinuation. Patient 2 developed moyamoya 8 months post-HCT during tacrolimus taper without other GVHD symptoms. Response to steroids was noted, so tacrolimus was restarted for residual neurological deficit. Neither patient developed chronic GVHD or left ventricular ejection fraction decline, and neither patient had disease relapse at follow-up of 30 and 16 months respectively. Patient 2 developed COVID pneumonia 16 months post-HCT and died while in CR. Patient 1 remains alive, in CR, and off immunosuppression nearly 3 years post HCT. Conclusion(s): Allogeneic HCT with PTCy at standard doses did not appear prohibitively toxic in patients with +21 when administered after reduced-intensity conditioning. In this case series, GVHD rates seemed consistent with larger series in patients without +21. Moyamoya development is associated with autoimmunity in patients with +21 and hence may have been GVHD-related5. Trisomy 21 should not be a barrier to patients otherwise eligible for HCT, even with PTCy prophylaxis.Copyright © 2023 American Society for Transplantation and Cellular Therapy
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SESSION TITLE: Problems in the Pleura Case Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Hematologic malignancies can often be complicated by pleural effusion due to leukemic infiltration of the pleura (1). Long term management of resulting chronic plural effusion can be complicated when there is evidence of trapped lung. Subsequent infection may lead to development of chronic empyema which can be difficult to manage in chronically ill patients (2). CASE PRESENTATION: A 65-year-old male with history of chronic myeloid leukemia status post stem cell transplant was admitted with dyspnea and cough. Computed tomography (CT) chest imaging revealed increased volume loss on the left with new air fluid level in a chronic left pleural effusion. (Image 1) Patient's history was significant for chronic left pleural effusion, which was first identified in 2015 and found to be a malignant effusion with evidence of leukemia involvement. Repeat imaging in 2018 (Image 2) revealed continued chronic pleural effusion. Patient was admitted in August 2021 with COVID-19 pneumonia and CT Chest showed chronic loculated left sided pleural effusion. Patient elected to continue to monitor the chronic effusion, which was completed as outpatient every 4 to 6 weeks (Image 3). He remained clinically stable until the presentation to a hospital in January 2022. The chronic empyema was initially managed with tube thoracostomy, intrapleural fibrinolytics and antibiotics. Cultures were significant for Moraxella catarrhalis and Streptococcus pneumoniae. He was determined to be a poor surgical candidate for decortication and treatment with empyema tube was initiated. The empyema tube was incrementally withdrawn as an outpatient and subsequently removed with good clinical recovery. DISCUSSION: Chronic empyema is characterized by thickened parietal and visceral pleura which limits the ability of the lung to re-expand. Surgical management with decortication is the definitive management, however, in poor surgical candidates, management becomes more complicated. Open pleural drainage with an open pleural window can be considered. An alternative option converts tube thoracostomy to open pleural drainage, as was utilized in this patient (2). While comparison of surgical vs non-surgical management of empyema suggests similar mortality (3), non-surgical management of chronic empyema needs more investigation to determine the optimal treatment modality. CONCLUSIONS: Empyema remains a difficult condition to manage. Treatment modalities of chronic empyema are limited in those patients who remain poor surgical candidates. Reference #1: Faiz SA, Sahay S, Jimenez CA. Pleural effusions in acute and chronic leukemia and myelodysplastic syndrome. Curr Opin Pulm Med. 2014 Jul;20(4):340-6. Reference #2: Biswas A, Jantz MA, Penley AM, Mehta HJ. Management of chronic empyema with unexpandable lung in poor surgical risk patients using an empyema tube. Lung India. 2016;33(3):267-271. Reference #3: Redden MD, Chin TY, van Driel ML. Surgical versus non-surgical management for pleural empyema. Cochrane Database Syst Rev. 2017;3(3):CD010651. Published 2017 Mar 17. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff no disclosure on file for Ravi Nayak;
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SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: The diagnosis of blastomycosis is often delayed due to its non-specific symptoms and imaging findings. Clinicians must have a high clinical index of suspicion to diagnose blastomycosis in a timely manner, especially in the setting of the current COVID-19 pandemic. CASE PRESENTATION: A healthy 44-year-old male presented to an urgent care center with complaints of cough, fevers, and malaise. CT scan of the chest revealed a left upper lobe mass concerning for rounded bacterial pneumonia versus malignancy. He was found to be COVID-19 positive. The patient was sent home with steroids and antibiotics. Three months later, a repeat CT scan of the chest was obtained which revealed progression of the consolidation and prompted further evaluation at the hospital. On presentation, he reported a persistent cough, weight loss, and the development of multiple painful nodules on his extremities and trunk within the past week. A skin lesion was biopsied. A bronchoscopy was also performed for biopsy and brushing. Biopsy of the skin lesion as well as specimens collected from the bronchoscopy resulted positive for Blastomyces. MRI of the brain demonstrated multiple enhancing lesions concerning for septic emboli. He was started on amphotericin B for treatment of disseminated blastomycosis with central nervous system (CNS) involvement. Repeat imaging of the brain and chest about 3 weeks after initiation of therapy showed interval decrease in the size of the lesions. He was then transitioned to oral itraconazole and discharged home. DISCUSSION: Blastomycosis is an endemic fungal infection that can affect immunocompetent and immunocompromised hosts. It tends to infect immunocompetent hosts more so than other invasive fungal infections. Symptoms can range from asymptomatic to rapidly progressive acute respiratory distress syndrome (ARDS). Disseminated blastomycosis has been reported in 20-50% of patients (1). In the above case, an immunocompetent patient developed pulmonary and dermatologic manifestations concerning for disseminated blastomycosis. Though he had no recent travel, occupational exposures, or contact with any construction work, the patient was living in an endemic area for Blastomyces. It is difficult to definitively ascertain if the patient already had pulmonary blastomycosis when he was diagnosed with COVID-19, but his extrapulmonary manifestations clearly developed after the diagnosis. Earlier detection and treatment of the pulmonary blastomycosis may have prevented the dissemination of the disease. CONCLUSIONS: This case serves as a reminder to consider other infectious etiologies, like endemic fungal infections, in the midst of the COVID-19 pandemic to prevent delays in treatment and progression of these diseases. Reference #1: McBride JA, Gauthier GM, Klein BS. Clinical Manifestations and Treatment of Blastomycosis. Clin Chest Med. 2017 Sep;38(3):435-449. doi: 10.1016/j.ccm.2017.04.006. Epub 2017 Jun 12. PMID: 28797487;PMCID: PMC5657236. Reference #2: Cafardi J, Haas D, Lamarre T, Feinberg J. Opportunistic Fungal Infection Associated With COVID-19. Open Forum Infect Dis. 2021 Jan 18;8(7):ofab016. doi: 10.1093/ofid/ofab016. PMID: 34621913;PMCID: PMC7928619. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff No relevant relationships by David Stoeckel
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Background: Remdesivir (RDV), a potent nucleotide inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, effectively reduces COVID-19 related hospitalization in outpatients at high risk for progression to severe disease. However, limited data exist on the safety profile of RDV in this population. Methods: We conducted a Phase III placebo-controlled study evaluating a 3-day regimen of RDV in non-hospitalized patients who are at risk for disease progression (age>60 years or underlying comorbid condition). Patients were randomly assigned 1:1 to receive intravenous RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo (PBO). The primary safety endpoint was the proportion of patients with treatment-emergent adverse events (AEs). AEs were evaluated through day 28 and lab abnormalities were evaluated through day 14. Results: 562 patients were randomized and initiated treatment (279, RDV;283, placebo). Baseline characteristics were balanced between groups. Thirty percent were ≥60 years old and most common comorbidities were diabetes mellitus (62%), obesity (56%;median BMI, 30.7 kg/m2), and hypertension (48%). RDV was well tolerated with a similar rate of any AEs between groups (Table). Patients treated with RDV had fewer Grade ≥3 and serious AEs (SAEs) compared to PBO, but had more study-drug related AEs, with the most common one being nausea (18 [6.5%] in RDV vs. 10 [3.5%] in PBO). Grade 3 or higher ALT elevation was reported in 1 (0.4%) RDV vs. 2 (0.7%) PBO treated patients. Median change from baseline in AST, ALT, and bilirubin was similar between groups (Table). Grade 3 or higher decrease in creatinine clearance (CrCl) occurred more often in RDV vs. to PBO treated patients (5.6% vs 1.9% respectively). Most decreases in creatinine clearance occurred within the normal serum creatinine range, occurred after completion of RDV therapy, and resolved on follow-up. Median changes in CrCl from baseline were similar between groups and no renal AEs were reported (Table). Incidence of cardiac-related AEs was similar between RDV and PBO groups. All bradycardia events occurred in the PBO group. No patient experienced a serious AE or drug discontinuation due to hypersensitivity. Conclusion: Treatment with RDV was safe and well tolerated in non-hospitalized patients with risk factors for COVID-19 disease progression. Patients in the RDV group had similar type, incidence, and severity of AEs and lab abnormalities as those receiving PBO.
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Background: Screening for atrial fibrillation (AF) is attractive because AF can remain undiagnosed and AF-related stroke can be prevented by anticoagulants (OAC). Methods: A randomized trial of screening for AF in individuals ≥70 years old without AF. Stroke and major bleeding are the efficacy and safety outcomes, ascertained from claims databases and electronic health records. Screening is done using a Zio®XT 14-day continuous cardiac rhythm patch monitor and compared, 1:1, to usual care. Use of OAC for detected AF is decided by patients and their physicians. The planned sample size was 52,000 recruited from U.S. primary care practices. Enrollment was severely hampered by the COVID-19 pandemic and stopped May 31, 2021 with 11,931 participants. Follow-up for stroke and bleeding events continues. Here, we report patch monitor findings from the 5,965 participants randomized to the screening arm. Results: 5,720 (96%) participants returned patches with analyzable data, the largest sample of patch monitor AF screening to date. Median (IQR) age was 75 (72, 79) years;57% were women. Median wear time was 13.9 (13.7, 14.0) days and median analyzable time was 98.4% (95.6, 99.5). 255 (4.5%) participants had AF, including 30 (0.5%) with 100% AF. 100% AF was more common in those age ≥80 (1.0%) than among younger participants (0.40%), p<.01. In the 225 participants with paroxysmal AF (PAF), median AF “burden” was 0.48% (0.016-2.5) of time monitored [78 (3.2, 454) minutes]. Median number of AF episodes during monitoring was 3 (1, 19). Median longest single AF episode was 60 (3-278) minutes. AF burden and length of longest episode were highly correlated (r=0.79, p<.001). Neither of these measures of PAF were associated with either age or sex. Conclusion: In GUARD-AF’s older primary care population, 0.5% of screened participants had persistent AF and 4% had PAF detected within 2 weeks of monitoring. In those with PAF, average AF burden was low but >25% had an episode of ≥4.6 hours of continuous AF, suggesting increased stroke risk. The need for stroke-preventive interventions (e.g., OAC) for screen-detected PAF remains a critically important research question.