Survival study of hospitalised patients with concurrent COVID‐19 and haematological malignancies

Abstract

The prevalence of cancer in patients with the novel coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 infection, is uncertain. In a pooled meta-analysis including 11 retrospective studies, the prevalence of cancer was 2%.1 Patients with cancer and COVID-19 have been reported to have a higher risk of suffering severe events (intensive care unit admission, invasive ventilation, death) in a retrospective study including 18 patients with cancer.2 One study reported 13 COVID-19 cases in a cohort of 128 hospitalised patients with haematological cancers, with no significant differences in baseline co-variates between patients developing or not developing COVID-19.3 In this series, cases with concurrent haematologic neoplasm and COVID-19 had a more severe manifestation of the disease, including acute respiratory distress syndrome (ARDS), and a higher death toll compared to 11 hospitalised healthcare providers with COVID-19 (8/13 vs. 0/11). In an attempt to reduce the risk of infection among patients with haematologic cancer, some recommendations have been published.4 A retrospective single-centre analysis of patients with haematological malignancies who developed COVID-19 during follow-up was conducted. Only hospitalised patients or those who underwent hospitalisation due to SARS-CoV-2 infection were included. Clinical data were obtained from electronic medical records. Cases were defined as COVID-19 by clinical, laboratory and imaging (X-ray) criteria. From March 9 to April 17, 34 cases were identified. Real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swab was performed in all cases, with 27 patients testing positive. The seven remaining patients who tested negative were included based on highly clinical and radiological suspicion. Patients were divided into survivors and non-survivors. Cytometric Bead Array was used to detect the protein levels of interleukin 6 (IL-6) of patients considered for tocilizumab treatment. The criteria for initiating tocilizumab were ARDS development and high IL-6 level (over 40 pg/ml, or lower if there was previous treatment with corticosteroids). Means between groups were compared using independent group t-test and Mann–Whitney test for normally and abnormally distributed data, respectively. Proportions for categorical variables were compared by chi-square test or Fisher's test when appropriate. Survival outcomes were analysed according to Kaplan–Meier estimator. Overall survival (OS) was defined as the time from COVID-19 diagnosis to death by any cause or to the last follow-up date. Cox proportional-hazards models were constructed based on univariate and multivariate analysis results, and variables for multivariate models were chosen based on clinical relevance. A complete description of the cohort is presented in Table SI. Table I summarises and compares co-variates between COVID-19 survivors (n = 23) and non-survivors (n = 11). Eight patients received weight-based dosing of tocilizumab during follow-up, 2/8 double-dose and 6/8 single-dose. IL-6 levels before and after tocilizumab administration, as well as the outcome of these patients is presented in Figure S1. IL-6 was tested in six other patients, only 1/6 – in the survivors' group – showed high levels (150 pg/ml), but was ARDS free. Median follow-up of the global cohort was 26 days, and OS after this time was 67% (Figure S2). At the end of follow-up, five patients were still hospitalised. OS is shown according to haematologic malignancy diagnosis before COVID-19 (Figure 1A). Patients were stratified into four groups: (i) lymphoproliferative disorders (LPDs), including non-Hodgkin lymphoma, Hodgkin lymphoma and chronic lymphocytic leukaemia; (ii) plasma cell dyscrasias, (iii) acute leukaemias and (iv) myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs). OS comparison was also performed according to haematologic treatment purpose at the moment of illness onset based on three groups: (i) induction to remission or salvage therapy, (ii) long-term treatment (maintenance of remission or stabilization of the disease) and (iii) no treatment (watch and wait or remission with no treatment) (Figure 1B). Five cases (1 AML, 3 MDSs and 1 MPN) were on life support at the time of COVID-19 diagnosis and were excluded from the survival analysis according to haematologic treatment purpose. Figure 1C shows OS depending on Quick SOFA (qSOFA) Score, CURB-65 Pneumonia Severity Score, and ECOG Performance Status (ECOG PS) at first hospital admission or at COVID-19 onset. OS according to the development of moderate or severe ARDS during the hospitalisation period is presented in Figure 1D. Univariate Cox proportional-hazards models are described in Table SII. Being over 80 years of age, qSOFA on admission/onset ≥2, ECOG PS on admission/onset ≥2, and ARDS development were statistically significantly associated with higher risk of mortality, while treatment with hydroxycloroquine or azythromycin was associat