The incidence of symptomatic osteonecrosis is similar between Japanese children and children in Western countries with acute lymphoblastic leukaemia treated with a Berlin‐Frankfurt‐Münster (BFM)95‐based protocol

Abstract

Summary In this study, we performed a retrospective analysis of a cohort of Japanese paediatric patients with B‐cell precursor (BCP)‐acute lymphoblastic leukaemia (ALL) treated with a Berlin‐Frankfurt‐Münster (BFM)95‐based protocol, to clarify the incidence, clinical characteristics, and risk factors of osteonecrosis (ON) in comparison to the ALL‐02 protocol. We identified a high frequency of ON with the BFM95‐based protocol compared to the ALL‐02 protocol. The incidence of symptomatic ON with the BFM95‐based protocol is comparable to previous studies in Western countries. We believe that the type of treatment regimen has more impact on the incidence of symptomatic ON in paediatric ALL than ethnicity.

Impact of asparaginase discontinuation on outcomes of children with acute lymphoblastic leukaemia receiving the Japan Association of Childhood Leukaemia Study ALL‐02 protocol

“…Together with suggestions in several previous reports, 24‐27 we believe that our findings support the idea that differences in the corticosteroid schedule at least partially explain why ALL‐02 protocols resulted in a very low frequency of allergic reactions to native L‐asparaginase 28 . Furthermore, we have also previously suggested that combined use of asparaginase and PSL, rather than dexamethasone, in this protocol might reduce the incidence of osteonecrosis 29,30 . Therefore, based on our results, 1 week of PSL, but not dexamethasone, should be used concomitantly with the first dose of L‐asparaginase during a series of administrations.…”

“…28 Furthermore, we have also previously suggested that combined use of asparaginase and PSL, rather than dexamethasone, in this protocol might reduce the incidence of osteonecrosis. 29,30 Therefore, based on our results, 1 week of PSL, but not dexamethasone, should be used concomitantly with the first dose of L-asparaginase during a series of This study has several limitations. In this protocol, patients received native L-asparaginase, rather than PEGasparaginase, which is regarded as less immunogenic and is currently widely used; however, frequencies of allergic reactions against asparaginase differ substantially even among protocols including only PEG-asparaginase.…”

The incidence, risk factors, and outcomes of symptomatic avascular necrosis of bone among Chinese pediatric patients with acute lymphoblastic leukemia

“…A survey in UK suggested Asian had the highest risk of ON, whereas the Japan Association of Childhood Leukemia Study (JACLS) group reported a low incidence rate of 1.5% among patients treated with ALL‐97 and ALL‐02 protocols. But subsequent JACLS ALL‐08 protocol based on Berlin‐Frankfurt‐Munster (BFM) 95 protocol showed a cumulative incidence comparable to Western groups 2,15–17 . In the recent report from Chinese Children's Cancer Group (CCCG) on CCCG‐ALL‐2015 study on 6141 patients of Chinese ethnic background, 0.1% and 0.6%–0.8% subjects had grade 3–4 symptomatic AVN in the low risk and intermediate‐to‐high risk treatment group, respectively 12 .…”

“…But subsequent JACLS ALL‐08 protocol based on Berlin‐Frankfurt‐Munster (BFM) 95 protocol showed a cumulative incidence comparable to Western groups. 2 , 15 , 16 , 17 In the recent report from Chinese Children's Cancer Group (CCCG) on CCCG‐ALL‐2015 study on 6141 patients of Chinese ethnic background, 0.1% and 0.6%–0.8% subjects had grade 3–4 symptomatic AVN in the low risk and intermediate‐to‐high risk treatment group, respectively. 12 The incidence of AVN in Chinese children with ALL appeared to be lower than that in Western populations.…”