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2851 Successful Outcomes of Children Simultaneously Diagnosed with Acute Myeloid Leukemia and Covid-19: The Role of a Mild Chemotherapeutic Induction Regimen

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Poster III
Hematology Disease Topics & Pathways:
Coronaviruses, AML, Diseases, Non-Biological, Therapies, chemotherapy, Pediatric, Study Population, Myeloid Malignancies, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Mecneide Mendes Lins, MD, MMSc1*, Juliana Teixeira Costa, MD2*, Alayde Vieira Wanderley, MD3*, Adriana Seber, MD, MS4, Cinthya Rocha, MD5*, Luciana Nunes Silva, MD2*, Laudreisa da Costa Pantoja, MD3*, Gustavo Zamperlini, MD6*, Valentino Conter, MD7* and Raul Ribeiro, MD8

1Pediatric Oncology Unit, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, BRA
2Hospital Martagão Gesteira, Salvador, Brazil
3Universidade Federal do Pará, Belem, Brazil
4Hospital Samaritano, Sao Paulo, SP, Brazil
5Pediatric Oncology Unit, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil
6Hospital Samaritano, Sao Paulo, Brazil
7Department of Pediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy
8Department of Oncology and Global Medicine, International Outreach Program, St. Jude Children's Research Hospital, Memphis, TN

Introduction: Children with newly diagnosed acute myeloid leukemia (AML) may have a high early mortality when resources are limited by infrastructure or by a widespread worldwide crisis, as being faced with the SARS-Cov-2 pandemic. Many elective treatments were postponed, but newly diagnosed AML is a life-threatening disease that needs prompt therapy. With acute shortage of infra-structure as intensive care unit beds, blood supply, medication, healthcare personnel, an optimal therapy must balance anti-neoplastic efficacy and the chance of treatment-related mortality. The induction chemotherapy of pediatric patients with AML living in low- and middle-income countries has been thoroughly discussed because early mortality remains 10%-20%, much higher than in developed counties. Mild treatment schemas have been used in Japan, China and Latin America with impressive results, comparable to other intensive induction regimens. Our objective is to describe the results of this mild induction regimen used in Brazil to treat children simultaneously diagnosed with AML and Covid-19 infections.

Methods: This is a retrospective multicentric trial including Brazilian children diagnosed with AML, also found to have a positive nasal and oropharyngeal PCR for SARS-Cov-2 and uniformly treated with mild induction protocol (“MAG”) that included Mitoxantrone at 5 mg/m2, by i.v. infusion over 4 to 6 hours once a day on days 1, 3, and 5 (three doses in total), Cytarabine at 10 mg/m2, subcutaneous (s.c.), q 12 h for 10 days (20 doses in total) and G-CSF 5 𝜇g/kg, s.c., once a day for 10 days (10 doses in total) [Bansal D, et al. Pediatr Blood Cancer. 2019 Nov 27:e28087].

Results: From March 15 to July 1, 2020, nine children from four different institutions were diagnosed with AML (Table 1). Their median age was 9 years (range, 5 to 18), 6 female gender, all but one diagnosed with Covid-19 by nasal PCR; one had typical chest CT and positive IgM. The institutions had previously agreed on following the same induction when treating AML children infected by the SARS-Cov-2. Five of the nine had severe illness, three of them needed mechanical ventilation and one did not need supplementary oxygen despite radiologically diagnosed pneumonia. Two children had mild symptoms and two were completely asymptomatic. All children tolerated MAG chemotherapy. Neutropenia lasted for a median of 29 days (17-33) and none of them had neither thrombotic complications nor acute renal failure. All children recovered from the Covid-19 infection and 8 of 9 already evaluable children achieved complete remission of the leukemia with MRD 0-1% after the two planned cycles. All patients are alive, on therapy.

Table 1: Patients characteristics

Pt# Age Gender AML-FAB Molecular Biology Cytogenetics CNS disease Severelly Ill Duration of Neutropenia (days) Response to 1st Induction Response to 2nd Induction COVID Symptoms Oxygen Therapy COVID Treatment Status
1 9 M M0 Negative Complex karyotype with del11 No No 33 0% blasts MRD 0,12% None No A Alive
2 8 F M2 Negative t(10,11) No Yes 26 1% blasts Too early Inflamatory syndrome Mechanical Ventilation A,C,IVIG Alive
3 17 F NOS Negative Normal No Yes 22 7% blasts MRD 1% Pneumonia Mechanical Ventilation A,I,O,C,H Alive
4 5 M M4Eo Inv16 Inv. 16 No Yes 22 2% blasts MRD negative Mild No - Alive
5 8 M M2 Amlto t(8;21) Yes Yes 19 0% MRD negative None No A Alive
6 8 F NOS Not done Not done No No 25 4% blasts MRD negative Pneumonia No A,O,C Alive
7 10 F NOS Not done Trisomy 22 No Yes 17 Too early Too early Pneumonia, Respiratory Distress Mechanical Ventilation A,O,C, IVIG Alive
8 10 F M5 ASXL1 Normal No No 31 0% Too early None No A,I,Cipro Alive
9 18 F M2 Negative Not done No No 27 0% MRD negative Mild No A Alive

A - Azythromycin; I - Ivermectin; C - Corticosteroids, O - Oseltamivir; IVIG - Immunoglobulin; H- Heparin; Cipro- Coprofloxacin

Conclusions: Against all odds, MAG was well tolerated in children and adolescents newly diagnosed with AML and active Covid-19, with no treatment-related mortality. All evaluable patients achieved remission and are currently proceeding therapy. The high prevalence of Covid-19 in our country may have to be taken into account in all oncological treatment strategies. With a shorter duration of neutropenia, the absence of mucositis or invasive fungal infections, MAG may be implemented in low- and middle-income countries as an optimal strategy to overcome induction mortality and improve outcome of children and adolescents with AML.

Disclosures: No relevant conflicts of interest to declare.

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