COVID-19–Related Chemotherapy Delays Common in Pediatric Patients With Acute Lymphoblastic Leukemia or Lymphoma

Children with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy) who were also diagnosed with a SARS-CoV-2 infection had chemotherapy treatments temporarily delayed, which could affect their outcomes, according to the results of a study published in JAMA Network Open.

Primarily, the investigators sought to describe the spectrum of outcomes and illness associated with COVID-19 and the administration of chemotherapy. Additionally, they aimed to analyze the differences in clinical characteristics between those who developed COVID-19 and those who did not during the allotted study period.

IV chemotherapy | Image Credit: © Sherry Young - stock.adobe.com

Patients included in the study cohort were aged 1 to 18 years with newly diagnosed ALL/LLy and had received treatment on the St Jude Total XVII protocol between March 2020 and June 2022, according to the investigators. In total, 308 patients were selected for the study, all of whom had received care at St Jude Children’s Research Hospital and/or its affiliate sites.

Of the total number of patients, 110 (36%) tested positive for SARS-CoV-2 at a median age of 8.2 (IQR, 5.3-14.5) years. Patients with SARS-CoV-2 infection were found to be older at diagnosis of ALL/LLy (median age, 6.7 [IQR, 3.7-12.8] years) than those without a SARS-CoV-2 infection (median age, 5.3 [IQR, 3.0-10.5] years) and were more likely to be of Hispanic ethnicity, according to the investigators.

The investigators noted that this rate of SARS-CoV-2 positivity among the cohort of patients was substantially higher than the cumulative incidence of 18% in the general pediatric population at the study sites, which they discussed as being reflective of the routine screening of patients in the study.

Most of the patients had COVID-19 in the maintenance phase of chemotherapy (101 [92%]), especially in the later stages of maintenance after week 20 (77 [70%]), the investigators wrote. Common symptoms among these patients were cough, fever, and rhinorrhea. Additionally, 36 patients (33%) were sent to the hospital at the direction of a clinician for a variety of symptoms, including fever and respiratory distress.

As a result of their SARS-CoV-2 diagnosis, chemotherapy was delayed until clinical improvement in their condition and/or the completion of antiviral therapy among 96 of the 110 patients (87%) for a median of 8 (IQR, 7-14) days, the investigators found. Treatment was held for all patients in the induction and consolidation phases of treatment, and for most patients in the maintenance phase.

Notably, the investigators found that chemotherapy was held more often and for longer periods in patients with severe disease compared with those without. At the same time, these treatment modifications were also found in 76% of patients with asymptomatic COVID-19.

Many of those with severe COVID-19 were adolescents, which is consistent with other studies on the topic, the investigators discussed. Possible explanations for this risk factor have been proposed, including fever restrictions on activities that can increase exposure to SARS-CoV-2 infection, the mature binding ability of the SARS-CoV-2 viral receptor and more intensive chemotherapy for older patients than in younger patients.

Despite the widespread practice of delaying or modifying chemotherapy treatment for patients with COVID-19, the investigators wrote that there are no clear data indicating the benefit of this practice. Additionally, they advocated for the minimization of these modifications and delays, and proposed instead giving a lower-intensity regimen, especially throughout the early phases of therapy.

The investigators made up any missed chemotherapy doses if a modification to therapy was made within 8 months of the patient's ALL/LLy diagnosis. They noted that receiving less than 95% of the prescribed dose of chemotherapy treatment in the maintenance phase of ALL treatment increases the risk of relapse 2.7-fold.

Furthermore, the investigators could not evaluate long-term outcomes of ALL/LLy due to the short-term follow-up period of the study. Since adverse events of ALL can occur up to 5 years following diagnosis, they suggested further studies be undertaken with longer follow-up periods and consideration of interruptions of chemotherapy.

Reference

Hashmi SK, Bodea J, Patni T, et al. COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma. JAMA Netw Open. 2024;7(2):e2355727. doi:10.1001/jamanetworkopen.2023.55727