COVID-19 in Chronic Myeloid Leukemia Patients - Brazilian Experience
Authors: Pagnano Katia B , Mourão Toreli Ana Carolina , Perobelli Leila Martins , Quixada Acy TS , Seguro Fernanda S , Bendit Israel , Delamain Marcia Torresan , Sapelli Jaqueline , Moura Muriel Silva , Bortolini Jaisson , Lourenço André LG , Gonçalves Natália N , Conchon Monika , Nucci Fabio Moore , Oliveira Luciene Da Cruz , Magalhães Gustavo HR , Funke Vaneuza , Tavares Renato , Centrone Renato Torrescasana , Santos Fabio PS , Fogliatto Laura , Palma Leonardo Carvalho , Clementino Nelma D , Hokama Paula OM , Boquimpani Carla M 
Published: November 2020

Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus Sars-Cov2. In Brazil, the first COVID-19 case was diagnosed in February 2020, and since then, the number of cases and deaths has increased exponentially, reaching 2.610.102 confirmed cases and 91.263 deaths on July 31st. Most people have a mild to moderate respiratory illness, but the clinical evolution may be severe in older adults and patients with comorbidities, such as cancer. There are few reports of COVID-19 in patients with chronic myeloid leukemia (CML). This ongoing study aims to collect data about COVID-19 in CML patients from Brazil and their outcomes.
Methods: This is an observational, multicentric, ongoing register study. Hematologists from private and public CML reference centers from different regions of Brazil were invited to report their cases of COVID-19 in CML patients. Altogether, those centers are responsible for the care of approximately 4336 CML patients. COVID-19 was classified as mild/moderate, severe (defined as tachypnoea [≥30 breaths per min], oxygen saturation ≤93% at rest, or PaO2/FiO2 ratio &lt;300 mm Hg) and critical (respiratory failure requiring mechanical ventilation, septic shock, or other organ dysfunction or failure that requires intensive care).
Results: Between March and July 2020, 24 institutions contributed to this analysis, and reported 28 COVID-19 cases in CML patients. Eighteen centers were from the South and Southeast regions, 5 from Northeast, and one from the Central region. There were 19 cases (67.9%) from the Southeast region, 8 (28.6%) from the Northeast, one from South (3.6%). The median age was 54 years (24-79), with 13 (44%) older than 60. Male patients were predominant (67.9%). There was one patient in the accelerated phase. There were two cases of COVID-19 simultaneous to CML diagnosis, 10 using imatinib, 7 dasatinib, 6 nilotinib, one ponatinib, one asciminib, and one patient in treatment-free remission after imatinib discontinuation. The median time of CML diagnosis was 7.0 years (0-26). Current CML response was: no hematologic response (n=8), hematologic response (n=4), major molecular response (n=9), MR4.0 or MR5.0 (n= 7). Eleven patients interrupted treatment temporarily during COVID. COVID-19 was confirmed by RT-PCR of oral and nasal swab collection (20) or serologic test (07). One case is suspect, awaiting confirmation. The majority of the patients presented at least one comorbidity (60%): hypertension (7), diabetes (3), chronic renal failure (1), dyslipidemia (2), arterial disease (2), cirrhosis (1), chronic obstructive pulmonary disease/emphysema (2), pulmonary hypertension (1), HTLV1 (1), obesity (n=1). COVID-19 severity: mild/moderate (19), severe/critic (9). Five out of 9 (55%) of the severe/critic cases were older than 60, 4/9 presented comorbidities and 5/9 (55%) had no major molecular response (MMR)(one was in accelerated phase, one newly diagnosed, and 3 with only hematologic response). Among the mild/moderate cases, 12/19 had optimal response (63%) and 7/19 (36%) had no hematologic response. Twenty-one patients recovered, 4 are still hospitalized, and 3 died from COVID: one newly diagnosed case with high leukocytes counts and with a simultaneous bacterial infection, one elderly patient with comorbidities treated with imatinib and one patient treated with nilotinib, with hematologic response. A fourth patient in the accelerated phase died 2 months after discharge, from disease progression and pulmonary infection. Conclusion: Although the sample size is still small to make conclusions regarding COVID-19 behavior in CML patients, the most severe cases occurred in patients not in MMR. The continued register of the cases will increase our knowledge about this disease and how to manage these patients.

Disclosures
Pagnano: Astellas: Other: Advisory Board and lecture; Novartis: Other: Advisory Board; EMS: Other: Lecture; Pintpharma: Other: Lecture. Magalhães:AstraZeneca: Speakers Bureau; Novartis: Speakers Bureau. Santos:Novartis: Other: Speaker fee; Bristol-Myers Squibb: Other: Speaker fee. Clementino:EMS: Other: Financial support for congress.