Clinical Characteristics and Outcome of COVID-19 in Turkish HematologicalMalignancy Patients

ABSTRACT

Patients with solid malignancies are more vulnerable to SARS-CoV-2 infection than the healthy

population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations,

such as in patients with hematological malignancies is a point of interest. We aimed to

analyze the symptoms, complications, intensive care unit (ICU) admission, and mortality rates

of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. In this

multicenter study, we included 340 adult and pediatric patients diagnosed as COVID-19 from

March to November. Forty-four (12.9%) patients were asymptomatic at diagnosis. In

symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8 %, and 41.8%

of the patients, respectively. Sixty-nine (20%) patients had mild SARS-Cov-2 disease,

whereas moderate, severe, and critical diseases were reported in 101 (29%), 71 (20%) and 55

(16%) patients, respectively. Two hundred fifty (73.8%) patients were hospitalized for

SARS-Cov2. Mortality related to SARS-CoV-2 infection was 26.5% in all cohorts; 4.4% in

those patients with mild disease, 12.4% in moderate disease, and 83% in severe and critical

disease. Active hematological disease, lower life expectancy related to primary

hematological disease, neutropenia at diagnosis of SARS- CoV-2, ICU admission, and first-line therapy used for COVID 19 treatment were found to be related to higher mortality rates.

Treatments with hydroxychloroquine alone or in combination with azithromycin were

associated with a higher rate of mortality in comparison with favipiravir use. In conclusion,

uncorrected proof patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of

Introduction

Millions of people have been infected with severe acute respiratory syndrome coronavirus-2

(SARS-Cov-2) worldwide. Comorbidities like diabetes mellitus, hypertension, chronic renal

failure as well as older age have been identified as risk factors for the severity of COVID-19(1-4).

Cancer patients also are found to be more vulnerable to SARS-CoV-2 infection than healthy

population in studies that mostly included solid malignancies (5-7). The increased risk of respiratory tract viral infections in hematological malignancy and hematopoietic stem cell transplantation(HSCT) patients has been previously reported (8,9). Either the underlying diagnosis or the treatments may influence the humoral and cellular immune function negatively, and result in a poor outcome. The clinical characteristics and risk factors that may be predictive for severity or mortality of COVID-19 in hematological

Methods

On behalf of the Turkish Society of Hematology, Infectious Complications and Supportive Care

Working Party, we retrospectively collected data from 25 centers in Turkey from March to

November 2020. The study was approved by both the Turkish Ministry of Health and the

Ethical Committee of Istanbul University- Cerrahpaşa School of Medicine(22-Sep2020/80350) and also locally by the participating centers.

Patients were included in the study according to the following criteria; a)if they had SARSCoV-2 PCR positivity via nasal swabs b) if they had negative PCR results but symptoms

related with SARS-CoV-2 with highly suggestive thoracal computerized tomography (CT)

findings. Patients who were followed up as both outpatient and inpatient for COVID were

eligible for the study Forms for data collection were e-mailed to participating centers.

Diagnosis and status of primary disease, treatment schedules for hematological malignancies,

time from the last treatment, life expectancy related to the hematological disease have been

recorded. Data regarding symptoms related to SARS-CoV-2 infection, hospitalization and

oxygen requirement, severity, complications organ involvement, laboratory parameters on

admission and treatments given for COVID 19 have also been investigated. Co-morbidities

were defined as diabetes mellitus, hypertension, chronic renal failure, chronic obstructive

pulmonary disease, cardiovascular disease, or pre-existing solid malignancy diagnosis were

also recorded.

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Patients who had autologous stem cell transplantation and were in the first 100 days after

transplantation were grouped as “auto-HSCT”. All patients who had allogeneic hematopoietic

stem cell transplantation have been accepted as “all-HSCT” patients irrespective of their

primary diagnosis and status of the disease.

The severity of SARS-CoV-2 infection was classified according to WHO definitions as (11):

Mild disease; symptomatic patients without findings of pneumonia or hypoxia. Moderate

disease; patients with signs of pneumonia, like cough, fever, dyspnea without signs of severe

pneumonia or SpO2 >90% on room air. Severe disease; patients with symptoms of

pneumonia and respiratory rate > 30/min; severe respiratory distress; or SpO2 <90% on room

uncorrected proof

The COVID 19 treatment of patients were determined according to guidelines released by

Turkish Ministry of Health. Due to the antiviral potency of hydroxychloroquine(HCQ), it has

been introduced as the initial treatment schedule alone or in combination with azithromycin

and favipiravir as salvage treatment. In the follow-up of the pandemic, favipiravir has been

moved to the first line in treatment consistent with the next version of guidelines.

The primary objective of the study was to identify the clinical outcomes and complications of

COVID-19 in patients with hematological malignancies and to determine the rates of

hospitalization, ICU admission, overall 45-day mortality rates. A secondary objective was to

find additional risk factors for mortality specifically defined for this group of

immunosuppressed patients.

Descriptive statistics were performed as the median in continuous and percentage in categorical

variables. The Cox regression model has been used for univariate analysis. Parameters that

could achieve p<0.20 were added into the multivariate Cox-regression model and significant

factors were detected with the stepwise method.

Results

Patient characteristics of 335 adults and 5 pediatric patients were summarized in Table

1. Median age was 59 years (7-93). COVID 19 was more frequent in males (M: F ratio=1,3).

The most common underlying hematological diagnosis was multiple myeloma(MM) (25%),

followed by acute myeloid leukemia(AML) (20%) and non-Hodgkin lymphoma(NHL)(18%).

The hematological disease status of the patients were shown in Table 1. Twenty-eight percent of

the patients had active disease. Twenty-eight of these patients were newly diagnosed but

treatment could not be started as a consequence of SARS Cov2 infection. The treatment

schedules for hematological malignancies were also summarized in Table 1. Treatment

protocols for the primary disease have been changed before the diagnosis of COVID 19 in 21%

of the patients.

Nasopharyngeal swab PCR positivity for SARS-CoV-2 was observed in 264 out of 340(77%)

patients. Forty-four (12.9%) patients were asymptomatic at diagnosis. In symptomatic

patients, fever, cough, and dyspnea were observed in 62.6%, 48.8 %, and 41.8% respectively.

In the all-HSCT group, 13% of the patients were asymptomatic. Fever was present in 55%,

cough in 50%, dyspnea in 28%, myalgia and malaise in 34% and 31% of the patients

respectively. In the auto HSCT group, 9 patients (64%) had a fever, 5 (35%) patients had cough

and malaise, 4 (28%) patients had dyspnea, whereas one patient (7%) was asymptomatic.

Median febrile days were 3 (1-20). Sixty-nine (20,2%) patients had mild disease, whereas

moderate, severe, and critical disease was reported in 101(29,7%), 71(20,8%), and 55(16,1%)

patients, respectively. ARDS was reported in 11 patients, sepsis and septic shock were

observed in 31 and 13 patients. Two out of five pediatric patients were asymptomatic, two had

severe and one had critical disease Severity of COVID 19 was not found to be related to

age, comorbidities, primary disease status, malignancy treatments, HSCT, and the type of

COVID 19 treatment.

In the Allo-HSCT group, mild, moderate, severe, and critical COVID 19 was observed in 18%,

44%, 13% and 10% respectively. Patients with graft versus host disease (GVHD) had the more

severe and critical disease in comparison with those without GVHD(p=0.03) In patients who

have been diagnosed as COVID 19 in the posttransplantation 30 days of auto HSCT; mild

disease was observed in 4 out of 14 patients, the moderate, severe and critical disease was

observed in 3, 4 and 2 patients, respectively.

Laboratory variables of the patients were summarized in Table1. Neutropenia and

lymphopenia at diagnosis was observed in 23% and 57%, respectively.

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