Management of acute myeloid leukemia in Covid 19 era

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Moroccan Journal Of Public Health Vol. 2, N° 1 (2021), 45-49 ISSN: 2658-8099

Research Article

Management of acute myeloid leukemia in Covid 19 era

Fatima Ezzahra RIDA

, Asmaa HARRACH

, Hasnaa JABRI²*, Meryem QACHOUH

, Mohamed RACHID

, Abdellah MADANI

, Mouna LAMCHAHAB

1: Department of clinical hematology and pediatric oncology, Ibn Rochd University hospital center, Casablanca 20000, Morocco 2: Department of Pneumology, Ibn Rochd University hospital center, Casablanca 20000, Morocco

*: Faculty of Medicine - Hassan 2 Casablanca University, Morocco

Corresponding Author E-mail: Ridafzaa@gmail.com

Article info

Received : April 2021 Accepted : June 2021 Online : July 2021

Keywords

Acute myeloid leukemia, Covid 19,

management, outcome

SUMMARY

The covid 19 pandemic has not spared patients with hematological malignancies. The hematologist community faces unprecedented challenge since the first identification of this new virus. In this study, we aim to describe characteristics and outcome of patients with acute myeloid leukemia (AML) diagnosed with covid 19 infection at different states of the disease. A total of 16 COVID-19-infected patients with AML were included; 4 (25%) patients were male. The average age was 37 years. 7 patients had a favorable, 7 intermediate and 2 high risk AML. We noted no case of hemorrhagic syndrome and only 1 patient developed a deep vein thrombosis. Treatment of AML was postponed in 11 patients. 4 patients who contracted the SARS-COV2 infection undergoing intensive myelosuppressive chemotherapy. 2 patients had severe events and only 1 patient died. Patients with AML may show favorable outcomes of COVID 19 infection even while treated with intensive chemotherapy.

Coronavirus disease has changed life overnight and impact the management of patients suffering from cancer in general and particularly patients with AML, we need more studies to better understand different aspects of this microscopic particle and its impact on the management of these patients.

1. Introduction

On January 30, 2020, the World Health Organization

declared the CoViD-19 pandemic as a public health emergency of international concern. Over 130 million cases have been confirmed worldwide with over 2 million deaths. In Morocco, the first case was identified in March 2

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and to date we count more than 500,000 cases.

Several studies suggest that cancer patients have a higher risk of serious events compared to non-cancer patients (39% vs 8%) [Gavillet et al. 2020].

Acute myeloid leukemia (AML) is a malignant disorder of the bone marrow which is characterized by the clonal expansion and differentiation arrest of myeloid progenitor cells. [Shallis RM et al. 2019]. Patients with acute myeloid leukemia may develop a Covid 19 infection concomitantly with the diagnosis or during the course of treatment, which compromises the therapeutic management in these patients.

We report a series of 16 patients followed for acute myeloid leukemia diagnosed with covid-19 managed at our department, and we aim to describe clinical characteristics and treatment outcome of these patients.

2. Material and methods

We carried out a retrospective study at the department of hematology of Ibn Rochd University Hospital of Casablanca over a 12-month period from March 30, 2020 to March 30, 2021, involving patients with acute myeloid leukemia having a concomitant infection with COVID 19.

The diagnosis of SARS infection -CoV-2 was based on the detection of the virus by real-time polymerase chain reaction (SARS-CoV-2 E-gene RT-PCR) in respiratory tract specimens. Epidemiological, clinical data, laboratory findings and treatment outcome were retrieved from the patient’s medical records.

3. Results

We enrolled 16 patients. The average age was 37 years [20-68], the sex ratio M / F was 0.33. No one has associated comorbidities apart from AML. 2 patients

developed SARS COV 2 infection at diagnosis, 8 at complete remission 3 at induction failure and 2 were under palliative treatment. The cytogenetic study of blast cells allowed patients to be classified into 3 prognostic groups according to European Leukemia Net (ELN), 7 patients had a favorable, 7 intermediate and 2 high risk AML.

Testing for SARs-COV2-RNA by RT-PCR was indicated in symptomatic patients in 44% and for screening in 56%.

Patients in which chest computed tomography (CT) was performed n=7 showed bilateral ground glass opacities in 5 cases and was normal in 2 cases. All the patients had received treatment according to the national protocol with oral hydroxychloroquine (200 mg *3/day for 10 days) in association with azithromycin 500 mg on day 1 then 250 mg per day from day 2 to day 7, vitamin c and zinc. 2 patients were admitted to the intensive care unit with the development of COVID pneumonia; one patient required noninvasive ventilation for 4 days with good progress and the 2nd patient had developed acute respiratory distress syndrome (ARDS) and required mechanical ventilation.

Deep vein thrombosis was observed in a single patient 20 days after infection. The control PCR on D14 was carried out in 2 patients and confirm the absence of SARS COV 2 infection. Serological follow-up was not done. No patient presented with hemorrhagic syndrome during this period.

Regarding treatment of AML during the COVID19 infection period, the treatment was delayed in 11 patients, 4 patients were undergoing intensive chemotherapy with grade 4 neutropenia and developed infection indoors despite isolation and hygienic measures. In our series, only one patient died due to a severe course of complicated COVID 19 septic shock.

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Table I. clinical and evolutionary characteristics of patients

Patients number n=16

Percent %

Prognostic groups according to ELN:

Favorable Intermediate High

7 7 2

43,7 43,7 12,5 Disease state:

At diagnosis Complete remission Failure

Progression Unevaluated

2 8 3 2 1

12,5 50 18,75 12,5 6,37 Symptoms at onset:

Fever Cough Myalgia

Respiratory distress Contact with infected Asymptomatic

4 3 2 2 1 7

25 19 12 12 6 44 Treatment site:

Medical service ICU

Home

6 2 8

38 12 50 Complications:

ARDS Sepsis Thrombosis

2 2 1

12 12 6 Evolution:

Favorable Death

15 1

94 6

Figure 1. Aspect of ground glass opacities in the two pulmonary fields producing a crazy paving appearance in one of our patients

4. Discussion: The The treatment of acute myeloid leukemia with intensive chemotherapy induces severe and prolonged neutropenia exposing the patient to a high risk of infection of bacterial, fungal or viral origin. [Ferrara et al. 2020]. The exact incidence of COVID-19 in patients with cancer in general, and in patients with leukemias in particular, is unclear. [Zeidan et al. 2020]. The prognosis of covid-19 infection in patients with cancer and hematological malignancies is difficult to determine, and remains controversial. Initial reports from China suggested that patients with cancer are at a 3·5 times higher risk of severe COVID-19 compared with the general population [Liang et al. 2020]. Other data, based on post- transplantation cohorts, argue that, unlike common viral agents, coronaviruses do not cause more severe disease [L. D’Antiga, 2020]. In Morocco, analysis of the causes of death linked to COVID-19 concluded that the most significant factors were; age ≥ 65 years, the presence of cancer and mal sexe. [Youbi 2020]. In our study;

25% were males. 2 patients required hospitalization in the intensive care unit, and death occurred in only one patient. In these struggling times, the hematology staff face an enormous challenge, from diagnosis to treatment to various complications of AML. Regarding diagnosis, the similarity of clinical signs of SARS COV infection and leukemia may delay the diagnosis of covid19 in these patients. As 50–75

% of patients with acute leukemia are febrile at diagnosis, they are at high risk of missed or delayed diagnosis. [ Burke et al. 1976]. In addition

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to diagnostic delay, most patients may suffer from postponed chemotherapy, which may negatively affect prognosis, particularly in young (< 60 years-old) patients with favorable- or intermediate-risk disease. [Gavillet et al. 2020][1].

The American Society of Hematology has recommended postponing induction 1 in patients with symptoms of COVID 19 until clinical signs improve. Low-intensity therapies, such as a hypomethylating agent with VENETOCLAX can be safely administered on an outpatient basis.

[DiNardo et al. 2019]. Since the diagnosis of the first case in our unit, all our patients are screened before admission. This systematic screening for COVID 19 by RTQ-PCR detected infection in seven asymptomatic patients. For this group of patients, AML treatment was delayed for up to 14 days. This preventive action made it possible to avoid the initiation of immunosuppressive treatment in patients with silent active infection.

For patients in remission awaiting consolidation treatment, our strategy was also based on the reduction of aracytine dose from 3g / m2 to 1.5g / m2 with the reduction in the number of cycles from 4 to 3. In the literature based on findings from the MRC 15 trial, lowering the dose of cytarabine from 3 gm / m2 to 1.5 gm / m2 could minimize the duration of myelosuppression without sacrificing long-term outcomes. [Burnett et al. 2013] More- over, reducing the number of cycles from four to three may also lower the risk of infection. [Mayer et al. 1994]. Use of myeloid growth factors further reduces the duration of neutropenia, the risk of infection, and the need for hospitalization.

5. Conclusion

In our study, we found no evidence that acute myeloid leukemia significantly influenced the course of the disease;

even immunocompromised patients on cancer treatment may have a favorable outcome. Optimized management of COVID-19 is essential in order to identify and treat patients with more severe disease progression.

Understanding and managing this pandemic remains a challenge, whether the prevention against its spread, the appropriate treatment or vaccination.

Conflicts of Interest

The authors declare that they have no competing interest

Acknowledgements

The authors thank the pneumology department, the radiology department, the reanimation department and the laboratory of Ibn Rochd university hospital of Casablanca for their contribution to the diagnosis and treatment of patients.

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