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1001 Challenges in Treatment of Patients with Acute Leukemia and COVID-19 – a Series of 12 Patients

Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Hematology Disease Topics & Pathways:
SARS-CoV-2/COVID-19, Coronaviruses, viral, Leukemia, AML, Adult, Diseases, Non-Biological, Infectious Diseases, Lymphoid Malignancies, Study Population, Myeloid Malignancies, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Susanne Ghandili1*, Susanne Pfefferle2*, Kevin Roedl3*, Piet Sonnemann1*, Panagiotis Karagiannis1*, Olaf Boenisch3*, Stefan Kluge3*, Stefan Schmiedel4*, Harald Ittrich5*, Holger Rohde2*, Marc Lütgehetmann2*, Katja Weisel, MD6*, Carsten Bokemeyer, MD7*, Dominic Wichmann3*, Walter Fiedler, MD8, Dominik Jarczak3* and Franziska Modemann1*

1Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg Eppendorf, Hamburg, Germany
2Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg Eppendorf, Hamburg, Germany
3Department of Intensive Care Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany
4I. Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Hamburg Eppendorf, Hamburg, Germany
5Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany
6Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
7Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
8Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Hospital Eppendorf, Hamburg, Germany

We report a series of twelve patients with acute leukemia (median age 60 years, 75% male) and concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted or were already under treatment in our department between March and May 2020. Patient cohort at SARS-CoV-2 diagnosis included patients with newly diagnosed acute myeloid leukemia (AML, n=3) or acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL, n=1) and patients who were already under leukemia-specific treatment (AML: n=5; ALL: n=3).

Main observation was a sevenfold higher rate of severe and critical courses compared to average Chinese population. We scored mild or moderate courses of coronavirus disease 2019 (COVID-19) in three (25%) and severe and critical courses in nine patients (75%) including two deaths and 42% of severe acute respiratory distress syndrome (ARDS). Eleven patients (92%) developed COVID-19 pneumonia.

In all four ALL patients, specific therapy could be administered with only small delays or modifications whereas all 3 patients with newly diagnosed AML developed critical courses with ARDS, especially those treated with intensive chemotherapy. Six patients received therapy with azacytidine and venetoclax for newly diagnosed or refractory AML. Only two had to be intubated for 12 or four days respectively and none died. This combination may be less toxic than intensive chemotherapy and may be used as a bridge to further therapy.

Additionally, the prolonged and severe course of clinical disease is paralleled by the virological findings showing that during the long observation period of eight weeks in two patients SARS-CoV-2 was still detectable and just 60% developed SARS-CoV-2 IgG/IgM (IgM and IgG tested against viral spikeprotein (S1/S2) and nucleoprotein (N)). Furthermore, SARS-CoV-2-RNA was detected in upper respiratory tract samples of all patients by RT-PCR at very high concentrations (average 1x107 RNA copies/ml) and all tested patients showed viremia with an average of 1x103 RNA copies/ml at diagnosis of SARS-CoV-2 infection. Remarkably, four patients had persistent viremia on day 14. Highest virus RNA load with increasing titers over the observation period were observed in the two patients who had a fatal outcome, which highlights importance of monitoring RNA load in plasma in critically ill patients.

We also studied regularly performed chest computed tomography images during clinical course which showed bilateral, mainly peripheral ground glass opacities with or without consolidation matching the typical finding of COVID-19 despite of aplasia.

In summary, SARS-CoV-2 infection has a more complicated course in leukemia patients than in the general population and is accompanied by high viral titers in swaps and viremia. Reduced intensity therapy is warranted especially in AML patients.

Disclosures: Karagiannis: Abbvie Inc.: Other: Shareholder. Kluge: Astellas: Honoraria, Other: Consultant honoraria; Xenios: Other: Consultant honoraria, Research Funding; Bard: Honoraria; Basilea: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Fisher&Paykel: Research Funding; Fresenius: Honoraria, Other; Baxter: Honoraria, Other; Biotest: Honoraria; CSL Behring: Honoraria; Cytosorbents: Honoraria; Orion: Honoraria; MSD: Honoraria, Other; Philips: Honoraria; Arjo-Huntleigh: Honoraria; Astra: Honoraria; Gilead: Honoraria, Other; Ambu: Research Funding; E.T.: Research Funding; View Ltd.: Research Funding; Sedana: Honoraria; Sorin: Honoraria; Xenios: Honoraria; Zoll: Honoraria; AMOMED: Other. Rohde: Pfizer: Honoraria; Infectopharm: Honoraria; Correvio: Honoraria; Accelerate Diagnostics: Honoraria; Advisor: Honoraria; Pfizer: Honoraria; Shionogi: Honoraria; MSD: Honoraria. Weisel: Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Adaptive: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Bokemeyer: Merck Serono: Consultancy, Other: travel accomodations; Lilly/ImClone: Consultancy, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria; AstraZeneca: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Other: travel accomodations, Research Funding; BerGenBio: Research Funding; Astellas: Research Funding; Apellis Pharmaceuticals: Research Funding; Amgen: Research Funding; Alexion Pharmaceuticals: Research Funding; Agile Therapeutics: Research Funding; ADC Therapeutics: Research Funding; Abbvie: Research Funding; AOK Health Insurance: Consultancy; GSO: Consultancy; Bayer Schering Pharma: Consultancy; Taiho Pharmaceutical: Research Funding; Springworks Therapeutics: Research Funding; Rafael Pharmaceuticals: Research Funding; Novartis: Research Funding; Nektar: Research Funding; MSD: Research Funding; Millenium: Research Funding; Karyopharm Therapeutics: Research Funding; Janssen-Cilag: Research Funding; Isofol Medical: Research Funding; IO Biotech: Research Funding; Incyte: Research Funding; GSK: Research Funding; Glycotope GmbH: Research Funding; Gilead Sciences: Research Funding; Eisai: Research Funding; Daiichi Sankyo: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Blueprint Medicines: Research Funding; Pfizer: Other; Sanofi: Consultancy, Honoraria, Other: travel accomodations; Bayer: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Merck KGaA: Honoraria. Wichmann: MSD: Honoraria; Gilead: Honoraria; Pfizer: Honoraria; Correvio: Honoraria. Fiedler: Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accomodations; Celgene: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accomodations; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support in medical writing; BMS: Honoraria; Gilead: Honoraria; Ariad/Incyte: Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Other; BerGenBio ASA: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support in medical writing; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accomodations, support in medical writing, Research Funding. Modemann: Servier: Honoraria, Other: travel accomodations; Daiichi Sankyo: Research Funding; Incyte: Other: travel accomodations; Gilead: Other: travel accomodations; Jazz Pharmaceuticals: Other: travel accomodations; Novartis: Other: travel accomodations; Teva: Other: travel accomodations; Pfizer: Other: travel accomodations; Amgen: Other: travel accomodations.

*signifies non-member of ASH