key: cord-1054764-md61rehn
authors: Singh, Suvir; Singh, Jagdeep; Paul, Davinder; Jain, Kunal
title: Treatment of Acute Leukemia during COVID-19: Focused review of evidence
date: 2021-01-12
journal: Clin Lymphoma Myeloma Leuk
DOI: 10.1016/j.clml.2021.01.004
sha: d74ba2cb47c80b815acea38987561e852655cd64
doc_id: 1054764
cord_uid: md61rehn

The COVID-19 pandemic is an unprecedented healthcare crisis, and has led to over 1.5 million deaths worldwide. The risk of severe COVID-19 and mortality is markedly raised in patients with cancer, prompting several collaborative groups to issue guidelines to mitigate the risk of infection by delaying or de-escalating immunosuppressive therapy. However, delayed therapy is often not feasible for patients requiring treatment for acute leukemia or stem cell transplantation. We provide a focused review of the recommendations and evidence for managing this high risk group of patients while minimizing the risk of COVID19 infection, and provide a small snapshot of treatment data from our centre.

The severe acute respiratory syndrome -coronavirus 2 (SARS-CoV2) is an RNA virus which has led to an ongoing global pandemic. (1) Since its first description in December 2019, it has caused over 68 million infections and 1.5 million deaths over a one year period. Illness caused by this virus (named Coronavirus Disease -2019, or COVID-19 for short), can present as a spectrum from an asymptomatic carrier state to respiratory failure and multiorgan dysfunction. (2) The COVID-19 pandemic is an unprecedented crisis, and demonstrates a case fatality rate (CFR) of approximately 5 to 7%. (3) The CFR under-estimates the burden of infection, as patients with mild or asymptomatic disease are excluded, which may constitute over 50% of all cases. A better measure is provided by the infection fatality rate (IFR) and estimated to range from 0 to 1.6%. (4) Meta-analysis of clinical data has shown that approximately 30% patients require ICU admission, and the mortality rate in this subset approaches 39%. (5) The risk of severe disease and mortality is higher is certain subgroups, including those with comorbidities, active malignancy or advanced age (>60 years). (6) Due to disease and treatment related factors, patients with cancer are at an especially high risk of severe disease and have been noted to have a mortality rate exceeding 25%. (7) (8) This initial surge in mortality in cancer patients prompted several groups to recommend delay or deferral of curative chemotherapy to minimize the risk of mortality due to severe COVID-19. (9) However, delays in treatment of patients with hematologic malignancies, especially those with acute leukemia planned for chemotherapy or transplantation is associated with a risk of disease progression and inferior outcomes. For these patients, added efforts must be made to minimize infection risk while ensuring continuation of treatment. A judicious modification of protocols at each stage of treatment to minimize the risk of infection must be attempted, depending on disease status and local factors. (10) We provide a focused review on the current evidence and recommendations for management of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) during the COVID pandemic. Table 1 . The first study is a database review from Turkey, which included all patients with COVID-19 infection from a national database. (18) Out of a total of 1,88,897 patients, 740 were noted to have concurrent COVID-19 and hematologic malignancy. This subset of patients was compared to another 740 patients with COVID without hematologic malignancies and found to have a twofold higher mortality (13.8% vs 6.8%). The second study is a large retrospective database analysis of US health records, which compared outcomes with hematologic malignancies in patients who were diagnosed recently versus historic cohorts. This study included 73 million records and identified 17,000 patients with COVID-19, out of which 420 had co-existent blood cancer. A significantly higher risk of death was noted in patients with COVID-19 compared to those without COVID. (15) The third is a meta-analysis which included 34 adult and 5 paediatric studies comprising 3377 patients and demonstrated an initial mortality of 34% for all patients with hematologic cancers, which was much higher for patients > 60 years of age. (https://www.idsociety.org/practice-guideline/covid-19-guideline-infection-prevention/) It is recommended that the testing be performed as close to treatment initiation as possible, ideally no more than 2-3 days in advance. As patients often have repeated visits or re-admissions for treatment, frequent testing at every visit is not recommended, but regular screening for symptoms should be performed. Similarly, ASCO provides a framework for cancer care delivery during the COVID19 pandemic (https://www.asco.org/asco-coronavirus-resources/care-individuals-cancerduring-covid-19/general-information-about-covid-19). Before patients are admitted or enter a cancer care facility, screening for symptoms must be conducted, along with compulsory mask use.

Patients who have symptoms of cough, fever, myalgias, headache or dyspnea should be triaged for assessment so that testing for COVID19 and appropriate site of management can be decided.

Physical measures such as social distancing, patient isolation and visitor restriction must be followed. Simple measures such as screening, masking (21) and social distancing (22) 44) As ALL is curable disease in many age groups, it is recommended that priority be given to minimizing treatment delays. These principles are even more pertinent in the paediatric age group, where excellent long term outcomes are noted with strict compliance to treatment protocols. (45) For patients with ALL on treatment who developed COVID-19, therapy may have to be temporarily halted. The ASH guidelines recommend that treatment delays, if any, must not exceed 2 weeks. A decision to restart or withhold treatment must be made on a patient to patient basis, considering the phase of treatment, presence of neutropenia, additional infections and remission status. (54) It is vital to adapt these guidelines to local practice, as a delay of 1-3 months may not be feasible for certain high risk patients. This principle is mirrored in the ASTCT guidelines, which recommend consideration of a donor with recent infection after 28 days on a case to case basis. (23) Our centre's data on COVID-19 and hematologic malignancies

We recently submitted data on in-patient management of hematologic cancers from our centre, a 99 bedded cancer unit of a 1600 bedded teaching hospital (National Medical Journal of India, Manuscript 620_20, under issue preparation). The data has been updated since then, and the following is a short summary highlighting the steps taken to mitigate the risk of COVID-19 in this patient subset. 

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