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INTRODUCTION: Chimeric antigen receptor T-cells (CAR-T) represent a promising immunotherapeutic approach in the treatment of refractory malignancies, but carry the risk of unique inflammatory toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In moderate to severe cases, these toxicities necessitate intensive care unit (ICU) admission for aggressive support and management. DESCRIPTION: A 63-year-old male with a history of pulmonary embolism, prostate cancer with resection and relapsed/refractory IgG-kappa multiple myeloma (diagnosed 4 years earlier and status-post multiple chemotherapy regimens) was admitted for conditioning chemotherapy and CAR-T cell infusion. 1 day post-infusion on the ward, he developed CRS and ICANS, with fever and altered mental status, for which he received tocilizumab, dexamethasone, and anakinra, in addition to empiric antibiotics. He progressed with worsening hypotension and encephalopathy and was admitted to the ICU and required vasopressors, pulse-dose steroids, and siltuximab. A nasal swab was performed to rule out COVID-19, following which he developed persistent epistaxis, requiring packing and, after aspiration of blood, intubation for airway protection. Laboratory data showed anemia and thrombocytopenia, prolonged PT and aPTT, low fibrinogen, and elevated levels of ferritin of 44,124 mg/ mL, D-Dimer of 1.35 mug/mL, interleukin-6 of 8,595 pg/ mL, interleukin-10 of 1,042 pg/mL, tumor necrosis factor- alpha of 103 pg/mL, and interferon-gamma above 244 pg/mL. The patient received numerous red cell and platelet transfusions, aminocaproic acid, cryoprecipitate, and additional packing and thrombin application by ENT before his epistaxis was controlled. Ultimately, he was weaned from vasopressors, extubated after two weeks and transferred out of the ICU, discharged to rehabilitation, and later home. DISCUSSION: Severe CRS can be associated with hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation (DIC), which can lead to lifethreatening bleeding as demonstrated in our patient. Effective and timely treatment of bleeding associated with DIC and severe CRS can be life-saving. It behooves the intensivist to recognize the toxicities of CAR-T as therapeutic applications broaden in the coming years.
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TOPIC: Chest Infections TYPE: Global Case Reports INTRODUCTION: Recent data suggest that patients with advanced solid and hematologic malignancies are more likely to have prolonged SARS-CoV-2 viral shedding and poor outcomes with coronavirus disease 2019 (COVID-19) due to disease and therapy-related immunosuppression. We present a patient with lymphoma who had a very prolonged and ultimately fatal course of COVID-19 despite aggressive treatments. CASE PRESENTATION: A 39-year-old male was diagnosed with aggressive follicular lymphoma and received standard chemotherapy. Two years later, his disease recurs with transformation to diffuse large B-cell lymphoma and received Rituximab, Dexamethasone, Cytarabine, and Oxaliplatin and radiotherapy to T8-T10 for chord compression. Autologous hematopoietic stem cell transplant (HSCT) was planned but deferred because he tested positive for SARS-CoV-2 via nasopharyngeal (NP) swab RT-PCR. Over the next 12 months, he required hospitalization 7 times with fever, cough, progressive dyspnea, and diffuse lung opacities on chest radiograph. Chest CT revealed bilateral diffuse ground glass infiltrates. Bronchoscopy with BAL was positive for SARS-CoV-2 RT-PCR;lung biopsy revealed interstitial pneumonitis but negative for other infectious pathogens. Overtime, he tested 6 times positive and 2 times negative for SARS-CoV-2 by RT-PCR. He was treated with antimicrobials, convalescent plasma, Remdesivir, and corticosteroids. Cytoxan was subsequently added as a steroid sparing agent. He had 3 negative and 2 positive SARS-CoV-2 IgG serology tests. On this last admission, he presented with hypoxic respiratory failure requiring ICU admission and mechanical ventilation. IL-6 levels peaked at 244. The cycle threshold (CT) values were in the teens suspicious of active viral replication. In ICU he was treated with proned positioning and received vasopressors, Remdesivir, and another course of IV corticosteroids. A year from the COVID-19 diagnosis, the patient's family decided to focus care on comfort, and he expired. DISCUSSION: Per our knowledge we are describing the longest case that suffered with COVID 19. He had a slowly progressive disease and inconsistent SARS-CoV-2 RT-PCR tests. Our case highlights the challenges in managing lymphoma patients, who due to B-cell dysfunction and treatment depletion of B-cells, may act as persistent shedders and sources of transmission. They harbor dysfunctional CD8+ T cells and have an increased likelihood of virally induced lymphopenia and high mortality. The efficacy of corticosteroids and IL-6 receptor inhibitors to treat COVID-19 in patients with lymphoma is unknown. Although these treatments may be helpful in suppressing the 'cytokine storm', they can impede viral clearance. CONCLUSIONS: Our case suggests that regular viral load testing and prolonged courses of antiviral therapies and use of convalescent plasma may need to be considered in patients with lymphoma and protracted COVID-19. REFERENCE #1: Aries JA, et al. Clinical outcome of coronavirus disease 2019 in haemato-oncology patients. Br J Haematol 2020 REFERENCE #2: Hueso T, et al. Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19. Blood 2020;136:2290-95 REFERENCE #3: Ji Hoon Baang Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient J Infect Dis. 2020 Oct 22 : jiaa666. Published online 2020 Oct 22 DISCLOSURES: No relevant relationships by Alina Dulu, source=Web Response No relevant relationships by Anna Ford, source=Web Response Advisory Committee Member relationship with Jazz Pharmaceuticals Please note: $1-$1000 by Stephen Pastores, source=Web Response, value=Consulting fee Grant Support for Clinical Trial relationship with Biomerieux Please note: $5001 - $20000 by Stephen Pastores, source=Web Response, value=Grant/Research Support No relevant relationships by Kate Tayban, source=Web Response
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TOPIC: Critical Care TYPE: Global Case Reports INTRODUCTION: Immune thrombocytopenia (ITP) has been associated with COVID-19. We present a case of a patient with COVID-19 who developed severe ITP associated with fatal hemorrhage. CASE PRESENTATION: A 50-year-old-female with history of treated breast and renal cancers presented to the emergency department with cough and fever for 10 days. Nasopharyngeal swab was positive for SARS-CoV-2. The patient was administered supplemental oxygen and empiric broad spectrum antibiotics. Her respiratory status rapidly declined necessitating invasive mechanical ventilation and admission to the ICU on Day 1 for severe ARDS. IV Remdesivir, Dexamethasone 6 mg IV daily, convalescent plasma and IV unfractionated heparin infusion were administered. Platelets were 219 x 109/L, fibrinogen 980 and D-dimer level 11.2. On Day 18 platelets fell to < 2 x 109/L, without evidence of schistocytes on peripheral blood smear. Coagulation and liver function tests, and autoimmune disease markers were normal. Heparin was discontinued. Anti-platelet factor 4 heparin antibodies and platelet autoantibodies were not detected. ITP secondary to COVID-19 was considered and methylprednisolone 1 mg/kg IV and IV immune globulin (IVIG) daily for 5 days and platelet transfusions to keep platelets >5 x 109/L were administered with improvement in platelets to >150 x 109/L on Day 23. On Day 25, platelets decreased to < 2 x 109/L, with melena and leg petechiae requiring red cell and platelet transfusions. She was re-treated with IVIG for 5 days, dexamethasone 40 mg IV daily and Romiplostim 2mcg/kg subcutaneous weekly with rise in platelets to >150 x 109/L on Day 31. She remained ventilator dependent and underwent tracheostomy on Day 32. Platelet counts remained >200 x 109/L and Romiplostim was discontinued on Day 73. On Day 85, platelets again fell to < 5 x 109/L, associated with massive gastrointestinal hemorrhage and fatal hemorrhagic shock. DISCUSSION: We believe that severe ITP with multiple relapses associated with COVID-19 was the most likely cause of the significant drop in platelet count that caused significant bleeding and death in our patient. We also observed a delayed onset in the clinical presentation of ITP and symptomatic COVID, unlike previous reports. The initial episode of severe thrombocytopenia was responsive to glucocorticoids and IVIG and later required higher doses of steroids and Romiplostim but recurred upon discontinuation of therapy. Fatal hemorrhage due to COVID-19-associated ITP is rare. A review of 45 cases of ITP in COVID-19 patients reported the majority of cases (75%) occurring in moderate-to-severe COVID-19. Severe life-threatening bleeding was uncommon with one death attributed to intracranial hemorrhage. CONCLUSIONS: Clinicians need to be aware of ITP as a severe complication of COVID-19 that should be diagnosed and treated promptly to avoid fatal bleeding complications, as was observed in our patient. REFERENCE #1: Bomhof G, Mutsaers PGNJ, Leebeek FWG, et al. COVID-19-associated immune thrombocytopenia. Br J Haematol. 2020 Jul;REFERENCE #2: Mahévas M, Moulis G, Andres E, et al. Clinical characteristics, management and outcome of Covid-19-associated immune thrombocytopenia. a French multicentre series. Br J Haematol. 2020 Aug;190(4):e224-e229. REFERENCE #3: Bhattacharjee S, Banerjee M. Immune thrombocytopenia secondary to COVID-19: a systematic review. SN Comprehensive Clinical Medicine 2020 DISCLOSURES: No relevant relationships by Alina Dulu, source=Web Response Advisory Committee Member relationship with Jazz Pharmaceuticals Please note: $1-$1000 by Stephen Pastores, source=Web Response, value=Consulting fee Grant Support for Clinical Trial relationship with Biomerieux Please note: $5001 - $20000 by Stephen Pastores, source=Web Response, value=Grant/Research Support No relevant relationships by Katherine Silvey, source=Web Response No relevant relationships by Kate Tayban, source=Web Response
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SESSION TITLE: Lessons from the ICU: What have We Learned about the Management of COVID-19 SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: The purpose of this study is to describe the characteristics and outcomes of critically ill patients with cancer and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We reviewed the clinical characteristics and outcomes of adult patients (> 18 yrs) with active or recent history of cancer and confirmed COVID-19 who developed acute hypoxemic respiratory insufficiency/failure with radiographic opacities and were consecutively admitted to two intensive care units (ICU) at Memorial Sloan Kettering Cancer Center between March 16 and May 27, 2020. The hospital adopted an early-intubation strategy during the first 4 weeks and a waiting period of 4 weeks before considering a tracheostomy. Pressure control ventilation and targeted tidal volume of 6 ml/kg predicted body weight and moderate to high PEEP was standard practice. Cases were confirmed through reverse-transcriptase–polymerase-chain-reaction assays performed on nasopharyngeal swab specimens. Data were manually abstracted from electronic health records. RESULTS: During the study period, a total of 290 patients were admitted to the two ICUs;90 (31%) patients with active (n=87) or recent (n=3) history of cancer had COVID-19 pneumonia. Mean age was 65 years;60% were male, 67% were White;49% had hypertension, 29% had diabetes mellitus;and 50% had a smoking history. 52 (63%) had solid tumors and 38 (37%) had hematologic malignancies. Advanced stage non-small cell lung carcinoma and breast carcinomas were the most frequent solid tumors and leukemia and lymphoma were the most common hematologic cancers. Vasopressors were required in 38 (42%) and CRRT in 8 (9%). In-hospital treatments for COVID-19 included remdesivir in 20%, convalescent plasma in 12%, hydroxychloroquine in 37%, azithromycin in 35%, corticosteroids in 56%, IL-6 inhibitors (tocilizumab, siltuximab) in 6% and IL-1 receptor antagonist in 1%. Acute respiratory failure (ARF) leading to invasive mechanical ventilation (MV) developed in 61 patients (68%) with a mean of 25 days on MV. Prone positioning (self or during MV) was implemented in 44 patients (49%). 18 patients (30%) were extubated after a mean of 11.5 days and 16 (26%) underwent a tracheostomy, 10 of whom (63%) were successfully liberated from MV. Thirty-six patients (40%) had a Do-Not-Resuscitate Order during their ICU stay. As of May 27, 24 (39%) of the 61 patients who required MV have died compared to 5 (17%) of the 29 non-ventilated patients. 40 patients (44%) were discharged home and 25 (28%) remain hospitalized. CONCLUSIONS: Over a third of cancer patients who developed ARF due to COVID-19 requiring MV in the ICU did not survive. CLINICAL IMPLICATIONS: Critically ill cancer patients with COVID-19 are at high risk of severe disease and mortality. DISCLOSURES: No relevant relationships by Christine Ammirati, source=Web Response No relevant relationships by Melissa Barzola, source=Web Response No relevant relationships by Sanjay Chawla, source=Web Response No relevant relationships by Michael Dang, source=Web Response Advisory Committee Member relationship with Pronia Medical Please note: $1001 - $5000 Added 06/02/2020 by Neil Halpern, source=Web Response, value=stock options Advisory Committee Member relationship with Airstrip Please note: $1-$1000 Added 06/02/2020 by Neil Halpern, source=Web Response, value=stock options No relevant relationships by James Isbell, source=Web Response Advisory Committee Member relationship with Jazz Pharmaceuticals Please note: $1-$1000 Added 07/17/2020 by Stephen Pastores, source=Web Response, value=Consulting fee Grant Support for Clinical Trial relationship with Biomerieux Please note: $5001 - $20000 Added 07/17/2020 by Stephen Pastores, source=Web Response, value=Grant/Research Support No relevant relationships by Kate Tayban, source=Web Response