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.




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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