COVID-19 in Pediatric Hematopoietic Cell Transplant Recipients: A CIBMTR Study

Background: Adult recipients of hematopoietic cell transplantation (HCT) are at a very high risk of adverse outcomes after COVID-19 (Sharma A, Bhatt NS, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. The Lancet Haematology. 2021 Mar 1;8(3): e185-93). While children are known to have better outcomes after COVID-19 compared to adults in general, data on risk factors and outcomes of COVID-19 among pediatric recipients of HCT are lacking.

Methods: Using the data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between March 2020 and May 2021, we describe characteristics, severity, treatment approaches, and outcomes of pediatric HCT recipients who were ≤21 years of age at COVID-19 diagnosis. All diagnoses, donor choice/graft sources, and conditioning regimens were included. Patient, disease, and HCT-related factors were described as frequency for categorical variables and median, range, and interquartile range (IQR) for continuous variables. The probability of overall survival after COVID-19 was calculated using the Kaplan Meier estimator. Additionally, an analysis was performed in the subset of allogeneic HCT COVID-19 cases from the United States (US) to identify risk factors for developing COVID-19. COVID-19 cases were compared with a cohort of all pediatric allogeneic HCT recipients without COVID-19 matched by the transplant center. Impact of hematopoietic cell transplant comorbidity index (HCT-CI), HCT indication, donor type, conditioning intensity, graft vs. host disease (GVHD) prophylaxis, and occurrence of acute and chronic GVHD on development of COVID-19 was examined using Cox proportional hazards model. Hazard ratio (HR) and 95% confidence intervals (CI) were provided. Cumulative incidence of COVID-19 among the US centers reporting at least 1 COVID-19 infection was also calculated, using death from any cause as a competing risk. P value <0.05 was considered statistically significant for the analyses.

Results: A total of 167 pediatric HCT recipients (allogeneic, allo: 135 and autologous, auto: 32) met study inclusion criteria. Median age at COVID-19 diagnosis for allo and auto HCT recipients were 15 years (range <1-21y) and 7 years (range 1-21y), respectively. Median time from HCT to COVID-19 diagnosis was 15 months (IQR 7-45) for allo recipients and 16 months (IQR 6-59) for auto HCT recipients. Forty-two percent (42%) of the patients had at least one comorbidity prior to HCT. Thirteen percent (13%) were receiving immunosuppression within six months prior to COVID-19 diagnosis. COVID-19 disease severity was mild in 87% of patients, while 4% of patients had severe disease requiring mechanical ventilation or supplemental oxygen. Only 36 HCT recipients (22%) received any COVID-19 directed therapy. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (range 1-179) for allo and auto HCT recipients, respectively. The overall probability of survival at 45 days was 95% (95% CI 90-99%) and 90% (95% CI 74-99%) for allo and auto HCT recipients, respectively (Figure 1). Forty-five (45) day survival was lower among recipients transplanted at the transplant centers outside the US [non-US recipients 85% (95% CI 71-95%) versus US recipients 98% (95% CI 93-99%)]. No deaths occurred in patients who had received a transplant between 2000-2013. The primary cause of death was COVID-19 in 54% of patients and primary disease in 38% of patients. In the subset analysis restricted to pediatric allogeneic HCT recipients transplanted at the US centers (n=34), the cumulative incidence of COVID-19 infection was noted to be 1.9% (95% CI 1.2-2.9%) at 6 months post-HCT and increased to 4.7% (95% CI 3.4-6.3%) by 1-year post-HCT. Cox regression analysis showed that compared to HCT-CI score of 0, patients with HCT-CI score of 1-2 were more likely to develop COVID-19 (HR 1.95; 95% CI 1.03-3.69, p=0.042). Underlying diagnosis, donor type, treatment exposures, or GVHD did not predict COVID-19 incidence.

Conclusions: This is the largest series to date summarizing the cumulative incidence, risk factors, and outcomes of pediatric HCT recipients with COVID-19. Patients with pre-HCT comorbidities were more likely to develop COVID-19. However, the overall disease severity and mortality after COVID-19 were low in this patient cohort.

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