Patients and Methods
Between January, 2000 and April, 2015 a total of 223 children and adolescents were diagnosed with ALL at McMaster Children’s Hospital (MCH) in Hamilton, Canada. Six of them were infants, less than 12 months of age, who received very intensive chemotherapy according to Interfant protocols20 and were excluded from this study. Among the 9 early deaths, 5 occurred during remission induction (2.3%) and one child was withdrawn from treatment by her family at the end of induction while another returned to his native country at the same juncture. The study sample of 217 were treated on regimens 00-001,21 05-00122 and 11-00123 of the Dana Farber Cancer Institute Childhood ALL Consortium in which MCH had been a member since 1985. These regimens were characterized by high cumulative doses of glucocorticosteroids and asparaginase. Details of their disease and clinical outcomes are given in Table 1. For the purposes of this report the study sample was followed until December 31, 2020.
It was our standard practice, in the time period 2000-2015, to undertake dual energy x-ray absorptiometry (DXA) on all children> 3 years of age at diagnosis and at intervals of 6 months thereafter for the duration of treatment; two years after remission induction24. These examinations were performed with Hologic densitometers QDR 4500A and Discovery A (Hologic Inc., Waltham, MA). Each whole body scan results in radiation exposure of 20 microSv, less than 1/10th of a chest x-ray.25 Local normative data on body composition,26 including bone mineral density (BMD),27 were generated for 3-18 year olds and corrections for height, age and weight (HAW) were developed for BMD of the lumbar spine.28
Children and adolescents with lumbar spine areal BMD (LS aBMD) Z scores of < - 2.0 and those who were less osteopenic but had related bony morbidity, e.g. fractures, were candidates for treatment with a bisphosphonate, oral alendronate in all of them. Alendronate was administered weekly, in doses according to body weight (Table 2), to coincide with scheduled clinic attendance for chemotherapy, and all patients received daily supplemental calcium in the form of TUMS to provide 30 to 40mg/kg/d. Alendronate was administered while the children were fasting, as recommended.12
The study was approved by the Hamilton Integrated Research Ethics Board, project 3479 C.
Statistical analyses
Patient demographics including BMD were summarized using descriptive measures expressed as mean (standard deviation) or median (minimum, maximum) for continuous variables and number (percent) for categorical variables. Associations between categorical outcomes and clinical groups were assessed using Fisher’s Exact test or chi-squared test. Impact of bisphosphonate therapy on BMD was tested using paired sample t test. The limit for statistical significance was set at two tailed α = 0.05. Statistical software SPSS version 26 (IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp) was used for analysis.