Bone fractures and avascular necrosis (AVN), the death of bone tissue caused by a lack of blood supply, can frequently complicate therapy for children with acute lymphocytic leukaemia (ALL), resulting in significant pain and physical disability.

These treatment-related side effects have been seen most commonly in ALL patients diagnosed in their early teenage years but can occur in children of any age.

This study, presented at the ASH 2015 conference by Dr Peter Cole, sought to determine if any of 19 common genetic variants are associated with increased risk of bone damage in children with ALL.

Investigators collected blood or bone marrow from 627 children in remission and sequenced their DNA.

Then they observed the children for signs of bone damage during post-induction therapy.

Researchers observed that 61 patients (9.7%) developed AVN and 138 (22%) suffered one or more fracture.

Of the patients tested, 20.6 percent had a specific genetic variant (2R/2R) in a promoter of thymidylate synthase (TS), an enzyme that is often linked to treatment resistance.

Compared to those with other TS variants, researchers estimate that patients 10 and younger with the 2R/2R genotype have a nearly three-fold higher risk of developing AVN.

Among older children, this variant was associated with a two-fold increased risk of bony fractures.

The results indicate that children under 10 years of age with ALL and the 2R/2R genetic variant should be monitored more closely for the development of AVN during therapy.

Watch the press conference and the video interview for more information.

Source: ASH