COVID-19 in Children, Adolescents and Young Adults with Hematological Malignancies

Background: COVID-19 in adults with cancer results in substantial rates of severe infection (>25%) and death (13%) that are more than two-fold those in adults without cancer. Data from a few cohorts of COVID-19 in children with cancer, most of whom had leukemia, suggest low hospitalization rates (<10%) for COVID-19 in pediatric cancer. However, among pediatric patients with hematological cancers, there is a paucity of data regarding COVID-19 in adolescent and young adults (AYA) or recipients of hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell (CAR-T) therapies. This study aims to define outcomes in COVID-19 in children and AYA with hematologic cancers receiving HSCT, CAR-T, or chemotherapy.

Methods: We retrospectively reviewed medical records of patients aged 25 years and younger treated at Children's Hospital Los Angeles for a hematological cancer between March 2020 and March 2021. These patients underwent COVID-19 nasopharyngeal (NP) PCR prior to any sedation, hospitalization, or in case of symptoms suggestive of COVID-19 infection. COVID-19 related hospitalizations were defined as hospital stays due to COVID-19 manifestations that necessitated inpatient care and excluded those that were solely for febrile neutropenia.

Results: We identified a cohort of 56 patients with PCR positive COVID-19 infection. The infected cohort had a median age of 11.5 years (2-24 years). A majority of the cohort was of Hispanic ethnicity (n=38, 67%), and 40% (n=22) were overweight or obese. 53 had leukemia (49 lymphoid, 2 acute myeloid, and 2 chronic myeloid), and 3 had lymphoma. Anti-cancer therapy included chemotherapy only (n=40), CAR-T (n=6), HSCT (n=6) or both HSCT and CAR-T (n=4).The median time from malignancy diagnosis to COVID-19 for the chemotherapy cohort was 11 months (0-119 months.) Median time from HSCT or CAR-T was 15 months (2-59 months.) 29 patients were in a highly immunosuppressive phase of anti-cancer therapy.

44 (79%) had symptomatic COVID-19. 18 (32%) patients required inpatient care for COVID-19 (COVID-19 related hospitalization.) 6 had critical/severe, 6 had moderate, and 44 had mild infection (WHO Criteria.) For patients with non-severe infection, the reasons for hospitalization were dehydration and tachycardia requiring intravenous fluids. All patients with critical/severe infection developed hypoxia; 5 required intensive care admission. One required invasive ventilation. Two patients had multisystem inflammatory syndrome; both had received CAR-T. Only one patient developed a new thrombus during COVID-19 infection. COVID-19 therapies included Remdesivir (n=9), steroids (n=5), convalescent plasma (n=3), azithromycin (n=2), hydroxychloroquine (n=1), and monoclonal antibodies (n=1.) 4 patients underwent multiple (2-6) COVID related hospitalizations.

Factors associated with a higher risk for COVID related hospitalization included recent steroid exposure (p=0.006), neutropenia (p=0.04), and lymphopenia (p=0.005.) Obesity or HSCT were not associated with a higher risk for hospitalization. 3 of 6 CAR-T recipients with B-cell aplasia had severe/critical infection, one of whom required 6 hospitalizations for COVID-19 and was COVID-19 PCR positive for 212 days. COVID-19 resulted in chemotherapy delays in 11 of 40 patients (delays ranged 2-39 days, median=14 days.)

Conclusions: While there was no mortality from COVID-19, in contrast to other pediatric cancer studies, several patients required recurrent hospitalizations, and there was a substantially higher COVID-19 related hospitalization rate in our cohort. Differences in demographics and immunosuppression between our and other studies may account for this discrepancy. Neutropenia, lymphopenia, and exposure to steroids were predictive of higher risk for hospitalization. Our data suggest higher severity of COVID-19 infections in CAR-T recipients with B-cell aplasia raising the possibility of an increased risk for COVID-19 morbidity in the setting of hypogammaglobulinemia. In contrast to studies reported from the general population, obesity was not associated with worse COVID-19 outcomes in our cohort of pediatric patients with cancer. Ongoing studies entail collection of retrospective clinical data and prospective clinical and immune biomarker data from additional patients.