medwireNews: Almost one in five children who undergo allogenic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs) experience at least one late occurring toxic effect, research shows.
Writing in The Lancet Child & Adolescent Health, Rachel Phelan (Medical College of Wisconsin, Milwaukee, USA) and co-authors say their findings “highlight the need for, and access to, multidisciplinary and lifelong follow-up for children undergoing HCT for NMDs.”
Phelan and team used the Center for International Blood and Marrow Transplantation Research database to identify 5790 patients (61% male) with NMDs who were aged 21 years or younger when they underwent HCT between 2000 and 2017.
The median age at HCT was 5.5 years and 59.0% of transplants were from unrelated donors. The most common reasons for HCT were severe aplastic anemia (21.2%), non-severe combined immunodeficiency (SCID) primary immune deficiency (14.6%), and SCID (11.2%).
Overall, 19.5% of patients had one late toxic effect and 6.6% had at least two late effects in the 7 years after HCT. The most common late effects were neurologic events (stroke and seizure) and renal failure, occurring at cumulative incidence rates of 9.4% and 8.1%, respectively.
Other late effects recorded up to 7 years were growth disturbance (5.0%), diabetes (4.9%), hypothyroidism (3.2%), gonadal dysfunction (2.6%), cataracts (1.9%), avascular necrosis (1.6%), congestive heart failure (0.6%), and myocardial infarction (0.2%).
The timing of late effect development differed depending on the type, with the cumulative incidence of neurologic events, renal failure, and diabetes increasing sharply during the first year then stabilizing.
The rates of avascular necrosis, congestive heart failure, and myocardial infarction showed a steadier increase during the first 5 years then stabilized, while the cumulative incidence of endocrine-associated late effects, namely growth disturbance, hypothyroidism, and gonadal dysfunction, continued to increase over time.
Phelan and colleagues identified several risk factors associated with individual late post-transplant toxic effects, including older age at HCT (≥10 years), having an unrelated donor source, use of a total-body irradiation condition regimen (16.4% of the cohort), myeloablative conditioning (54.6%), and development of graft-versus-host disease (GVHD; 23.4%).
The greatest risk increase was for avascular necrosis among children aged 15 years and older at the time of HCT relative to those aged 0–4 years, at an adjusted hazard ratio (aHR) of 19.9. This was followed by the risk for gonadal dysfunction among children aged 10–14 years or 15 years and older versus those aged 0–4 years, at aHRs of 12.2 and 11.9, respectively.
Other notable associations included a significant fourfold increased risk for gonadal dysfunction among individuals who received myeloablative conditioning versus those who did not, and 2.4- and 1.9-fold increased risks for avascular necrosis and renal failure requiring dialysis among people who developed GVHD relative to those who did not.
The researchers also observed that participants who underwent treatment more recently (2012–2017) were significantly less likely to develop renal failure (aHR=0.7), neurologic effects (aHR=0.4), and growth disturbance (aHR=0.4) than those treated between 2000 and 2005.
This may suggest “improvements in overall transplant approaches and supportive care,” Phelan et al remark.
The authors conclude that “coordination of care when transitioning from paediatric-focused to adult-focused practices is crucial due to the ongoing possibility of late-occurring chronic conditions and risk for loss to follow-up as patients age.”
In an accompanying comment, Hasan Hashem, from the King Hussein Cancer Center in Amman, Jordan, says the study offers “unprecedented analysis of post-HCT effects in young children and adolescents with NMD.”
He believes that the findings “are likely to influence protocols for NMDs and contribute to establishing lifelong multidisciplinary follow-up for children who received transplants for these conditions.”
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Lancet Child Adolesc Health 2024; doi:10.1016/S2352-4642(24)00167-6
Lancet Child Adolesc Health 2024; doi:10.1016/S2352-4642(24)00168-8