ALL tied to increased organ system toxicity in adolescent, young adult patients
Adolescent and young adult (AYA) patients treated for acute lymphoblastic leukaemia (ALL) were more likely to have an increased rate of toxicities in every organ system compared with children, according to a study presented at ASH 2017.
Researchers gathered data from the Pediatric Health Information Systems database in US and analysed 18,095 patients diagnosed with ALL, comprising 2,348 AYA patients (aged ≥15 years, 66.14 percent males) and 15,747 children (aged <15 years, 55.52 percent males). Of these, 79 percent had one admission and the remaining had two or more admissions. [ASH 2017, abstract 222]
Compared with children, AYA patients had higher rates of gastrointestinal system toxicities such as mucositis (11.29 percent vs 7.80 percent) and pancreatitis (2.34 percent vs 0.81 percent), and were more likely to be placed on total parenteral nutrition (10.35 percent vs 5.74 percent).
Rates of neurologic toxicities such as peripheral neuropathy (4 percent vs 2 percent) and seizures (3.11 percent vs 1.92 percent) as well as pulmonary diseases, including pleural effusion (5.88 percent vs 3.63 percent) and pneumonia (5.41 percent vs 3.96 percent) were also higher in AYA patients than children.
AYA patients were more likely to develop thromboembolic complications with higher rates of toxicities, specifically pulmonary embolism (0.60 percent vs 0.11 percent) and upper extremity (0.85 percent vs 0.25 percent) or lower extremity thrombosis (0.64 percent vs 0.29 percent) compared with children. Cerebral venous sinus thrombosis was not significantly different between the two age groups.
Other toxicities that were particularly high among AYA patients vs children were fungal infections (9.03 percent vs 5.89 percent), gram-negative bacteraemia (4.17 percent vs 3.11 percent), hypertension (18.99 percent vs 12.69 percent), and acute kidney injury (9.92 percent vs 4.69 percent), the latter accounting for the higher likelihood of undergoing haemodialysis (2.68 percent vs 0.99 percent).
When analysing the patients by weight, overweight patients were more likely to experience increased toxicities compared with non-overweight patients, according to Gupta.
“[Overall], AYA patients developed disproportionately higher toxicities from drugs commonly used in paediatric protocols for ALL, [but] we do not know why AYA patients are more sensitive than children to the same chemotherapeutic agents,” said lead author Dr Ajay Gupta from the Rainbow Babies & Children's Hospital in Cleveland, Ohio, US.“We do need prospective studies to assess whether stricter dose modifications will improve the toxicity profile of AYA patients with ALL,” Gupta said. “Some of the proposals to decrease toxicity in these patients include asparaginase activity level monitoring, prophylactic anticoagulation and antibiotics, setting upper dose-limits for overweight patients, and altering intrathecal chemotherapy doses.”