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

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.