Young adults endure greater toxicity, morbidity after AML treatment

ORLANDO – Adolescents and young adults treated for acute myeloid leukemia in U.S. children’s hospitals showed higher rates of toxicity across the board and more mortality than pediatric patients, according to a presenter at the ASH Annual Meeting and Exposition.

“Adolescents and young adults, also known as AYAs, are cared for by both pediatric and adult oncologists. ... Despite survival gain over the past decade in leukemia, AYAs continue to demonstrate a consistent survival disadvantage,” Mohamad G. Sinno, MD, fellow in the division of pediatric hematology, oncology and bone marrow transplantation at University Hospitals, Cincinnati, said during his presentation.

Sinno explained that AYA patients with AML treated with a pediatric protocol rather than adult protocol fare better in both event-free survival and OS. Researchers in this retrospective study used the Pediatric Health Information System to identify patients with AML admitted between 2004 and 2018 and aged 1 to 39 years. They then extracted relevant ICD-9 and ICD-10 diagnoses, procedures and medication codes.

In comparing the cohorts younger than 15 years (pediatric; n = 5,204) and 15 years or older (adolescent or young adult, AYA; n = 2,025), Sinno said the groups were well matched demographically.

In looking at overall mortality, the AYA group had a mortality rate of 23.4% while the pediatric group had a rate of 15.5% (P = .0001). For patients who underwent bone marrow transplant, there was no difference in mortality between the age groups. AYA patients had higher rates of ICU stays, intubation, norepinephrine and dopamine as well, Sinno showed.

“Compared to children, AYA patients developed markedly increased toxicity in every organ system and required more supportive medications and procedural interventions,” Sinno said. “They also had higher overall mortality, however in an additional analysis focusing on transplant patients found there was no difference.”

Looking at infections, AYA had higher rates of sepsis (6.8% vs. 4.41%, P < .0001), fungemia (4.93% vs. 3.39%, P < .0001), viremia (1.05% vs. 0.7%, P = .0018), CMV infection (2.88% vs. 1.91%, P < .0001), Escherichia coli (0.92% vs. 0.69%, P = .0384) and PCP infection (0.33% vs. 0.16%, P = .0035).

Sinno also showed that AYA had higher rates of neurologic and mental health complications. They had higher rates of peripheral neuropathy (0.65% vs. 0.32%, P < .0001) and seizure (0.13% vs. 0.06%, P = .0377). And AYA were more likely to have depressive disorder (8.59% vs. 1.75, P < .0001), anxiety (8.62% vs. 1.75%, P < .0001), sertraline (6.3% vs. 1.87%, P < .0001) and citalopram (3.02% vs. 0.33%, P < .0001).

At the cardiovascular level, the burden once again fell on AYA vs. the pediatric counterparts. AYA were more likely to have hypertension (14.22% vs. 9.61%, P < .0001), cardiomyopathy (2.73% vs. 1.3%, P < .0001) and heart failure (0.77% vs. 0.57%, P = .0496) as well as pulmonary embolus (0.38% vs. 0.08%, P < .0001), thrombosis (0.18% vs. 0.05%, P = .0004) and phlebitis (0.85% vs. 0.3%, P = .0496).

The AYA cohort also reported higher levels of respiratory and renal complications. They had higher rates of pleural effusion (6.25% vs. 3.74%, P < .0001), respiratory failure (4.76% vs. 3.6%, P < .0001), pneumonia (5.15% vs. 4.19%, P = .0002) and pulmonary fibrosis (0.49% vs. 0.3%, P = .0122) as well as acute kidney injury (10.23% vs. 4.76%, P < .0001) and chronic kidney disease (2.32% vs. 0.66%, P < .0001).

Lastly, AYA were more prone to gastrointestinal complications. They reported higher rates of mucositis (4.92% vs. 4.53%, P = .0195), acute pancreatitis (1.88% vs. 0.96%, P < .0001), GI hemorrhage (0.89% vs. 0.55%, P = .0006), hepatic necrosis (0.69% vs. 0.34%, P < .0001) and acute cholecystitis (0.17% vs. 0.16%, P = .0015).

Looking at discharge mortality as a primary outcome and the predictors thereof, AYAs had higher rates of ICU stay, which was the strongest predictor (HR = 13.3 vs. 10.5 for pediatric) while use of micafungin and amphotericin carried higher hazard ratios for AYAs, Sinno said.

“After adjusting for other factors ..., ICU stay and use of antifungals other than fluconazole were associated with an inferior outcome,” he said. – by Katrina Altersitz

Reference: Sinno MG, et al. Abstract 332. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.

Disclosures: Sinno reports no relevant financial disclosures.