In a look at long-term observational data on the clinical features and course of disease for children with autoimmune hemolytic anemia (AIHA), patients were frequently found to have an underlying immune disorder and considerable morbidity and mortality rates.
The findings also underscore the need for immune and genetic testing for these patients, said Rachael Grace, MD, MMSc, associate professor of pediatrics at Harvard Medical School, who presented the data at the 66th American Society of Hematology Annual Meeting and Exposition.
AIHA is a rare pediatric disease for which there is little guidance for evaluation and treatment and poor understanding of characteristics that affect prognosis, so researchers set out to assess a wide variety of features over a 10-year period. Patients, ranging from 3 months to 21 years old, were drawn from 15 institutions from the ITP Consortium of North America and diagnosed between 2011 and 2020.
There were 402 patients included in all, diagnosed at a median age of 7, and median length of follow-up was 2.7 years. Warm AIHA (wAIHA) was the most common subtype, at 64%.
Fifty-eight percent of patients had a single episode of AIHA that remitted, 8% had two episodes that remitted, but 42% of patients had multiple episodes or had a chronic course, Dr. Grace said.
Genetic testing, mainly a primary immunodeficiency panel or whole-exome sequencing, was done in 30% of patients, and pathogenic findings were seen in 28% of those tested, she said.
Secondary AIHA was common, with 15% having an underlying primary immunodeficiency; common variable immunodeficiency and autoimmune lymphoproliferative syndrome were seen most often in 49% and 33%, respectively. Sixteen percent were found to have some other autoimmune disorder, most commonly lupus or autoimmune neurologic disease.
Evans syndrome (ES) was seen in 37% of cases. Those with ES were more likely to be older at their first episode — 9 years old versus 5 years. They were also more than twice as likely to have genetic testing performed compared with those without ES and twice as likely to have pathogenic findings on genetic testing. They were also about twice as likely to have treatment with steroid-sparing agents at their first episode, Dr. Grace reported.
Several features were found to increase the chances of having a chronic or relapsing course of disease: wAIHA, with an odds ratio (OR) of 15.9; ES with an OR of 4.9; another autoimmune disorder at 3.0; and abnormal immune testing at 2.5 (p<0.001 for all).
Patients were given a median of two treatments at their first AIHA episode, with corticosteroids given 76% of the time, IVIG 25%, rituximab 18%, mycophenolate 6%, and sirolimus 6% of the time, Dr. Grace said. Many patients had a complete response, and most had at least a partial response. At subsequent episodes, there was a much higher chance of a non-response to corticosteroids compared with the initial episode at 38% versus 4%, Dr. Grace noted.
Those with secondary AIHA were also more likely to be older at first episode (8 years vs. 6 years) and to have wAIHA. Having secondary AIHA didn’t affect the response to treatment with steroids or with steroid-sparing agents, researchers found.
Of those who had ongoing follow-up, 27% of patients with wAIHA had active disease on treatment, 3% had active disease and were being observed, and 70% were in remission. The overall mortality rate was 9.4%, and mortality was not associated with an ES diagnosis, immunodeficiency or autoimmunity, the number of AIHA episodes, or the type of AIHA.
“These data support comprehensive immune evaluation in children with wAIHA,” Dr. Grace said. She added that a substantial proportion of those wAIHA have a chronic or relapsing course, and “this supports early consideration of steroid-sparing therapy.”
In a discussion after her presentation, Dr. Grace said the findings should spur more genetic testing.
“I think these data support that all patients with wAIHA require extensive genetic testing. We have these data from this cohort, and it’s a matter of allowing that to happen through the systems we have,” she said. “These are the data we need to change our practice, and we are missing children — and probably adults too — if they haven’t had it done, who have underlying immune issues because genetic testing is not being done in 70% of these patients.”
Overall, “these high morbidity and mortality rates require expanded testing, monitoring, and additional treatment approaches in this pediatric population,” the researchers concluded.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Grace RF, Steele M, Kalashnikova T, et al. Pediatric autoimmune hemolytic anemia is associated with a high incidence of an underlying immune disorder and high mortality rate. Abstract 795. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 9, 2024; San Diego, California.
