Toxicity profile and treatment delays in NOPHO ALL2008—comparing adults and children with Philadelphia chromosome‐negative acute lymphoblastic leukemia

Abstract

Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.

Osteonecrosis in children with acute lymphoblastic leukemia

“…Notwithstanding that the overall incidence of osteonecrosis was substantially higher (4.7%) 35 and exceeded that reported in the trial NOPHO ALL-2008 (3.1%), 36 and EORTC-CLG 58951 (2.5%), 37 it still remained lower than that of CCG, 38,39 35 14.5% 10-15 years; DFCI-ALL 00-01 41 14% 10-18 years). However, a factor which remained consistent throughout all the studies was that older children and adolescents are at a much higher risk of developing osteonecrosis.…”

“…[7][8][9][10][11]43,62 In contrast, the incidence is lower in adults undergoing ALL therapy. 36 Thus, the pathogenesis of osteonecrosis is likely strongly associated with factors being most prominent in adolescent age, thereby causing the highest vulnerability for osteonecrosis in this age.…”

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

“…Five-year cumulative incidence of fractures has been reported to be 10% to 15% with no overall incidence difference between post-induction prednisolone or dexamethasone, although for adolescents dexamethasone seems to be associated with a higher risk 73, 76 .…”

“…The cumulative incidence of symptomatic venous TE is 2 to 8% 90– 93 , but asymptomatic cases have been reported in up to 70% of patients 92, 94 . Risk factors for TE include the leukemia itself, older age, central line catheters, immobilization, infections, systemic inflammation, and therapy with asparaginase or corticosteroids or both 76, 90, 93, 95, 96 , whereas inherited thrombophilia risk factors, including common germline DNA polymorphisms, do not seem to play a role or at best remain uncertain 96 . The fatality rate of venous TE is highest in children with thromboses in cerebral veins, and studies on the benefits of anti-thrombotic prophylaxis, preferably with the novel oral anti-coagulants, are needed 90, 97, 98 .…”

Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia

“…[9][10][11] However, age remains the strongest and most consistently identified factor, with patients 10 to 20 years old at greatest risk. 10,11,[13][14][15] Given this age-related risk, the majority of children in prior investigations of genetic predisposition to osteonecrosis were .10 years. 10,15 However, because ALL is so common in young children, up to 40% of osteonecrosis cases develop in children ,10 years of age.…”