Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan Association of Childhood Leukemia Study Group

Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan Association of Childhood Leukemia Study Group
Osteonecrosis (ON) is a serious complication of ALL treatment and can affect quality of life on the long term. Incidence is variable and identified risk factors include older age, female sex, dose and type of corticosteroids, combination of dexamethasone and L-asparaginase, and ethnicity. This retrospective analysis of cohorts of Japanese patients with ALL examines the incidence, risk factors, and treatment of ON.
Incidence and characteristics of ON were determined in patients with ALL (Pre-B ALL or T-cell ALL) enrolled in 2 studies from the Japanese Association of Childhood Leukemia Study (JACLS) group (n=635 ages 1-15 years for ALL-97 and n=1,027 ages 1-18 years for ALL-02). In both studies, L-asp was administered with prednisolone and dexamethasone was not used.
24/1,662 patients had symptomatic ON during/after treatment. 15/24 were female. Most frequent site was the femoral head (17/24). 5-year cumulative incidence of ON in patients age 10 or older was 7.2% (ALL-97) and 5.9% (ALL-02), compared to most previous studies that report much higher incidence of ON, usually exceeding 10%. 11 patients required orthopedic surgery. In evaluating the risk factors, for both protocols the only significant risk factor was age greater than or equal to 10 years.
ALL-97 collected data prospectively while ALL-02 collected data retrospectively via questionnaire. Patients post BMT were excluded. Japan has a comparatively homogeneous population and thus their underlying genomic risk may be different from their genetically heterogeneous European or North American counterparts. Genomic data (such as SNP array data) might be helpful in untangling risk factors for ON.
Low frequency of ON in the JACLS studies compared to previous studies. Although the cumulative steroid dose and amount of dexamethasone was equivalent to previous COG/CCG/AIEOP trials, it was not co-administered with asparaginase so this may be an important risk factor. Genomic risk of ON was not assessed however and this may also be an important difference.