Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development

We assessed the clinical and treatment factors that predispose survivors of childhood acute lymphoblastic leukemia (ALL) to low bone mineral density ( BMD), Using quantitative computed tomography, we determined the frequency o f low BMD (defined as >1.645 standard deviations (SD) below the mean) in le ukemia survivors treated with multiagent chemotherapy including prednisone and antimetabolite. All participants had completed therapy at feast 4 years earlier, remained in continuous complete remission, and had no second mali gnancies. We statistically correlated BMD results with patient characterist ics and treatment histories. Among 141 survivors (median age, 15.9 years; m edian time after diagnosis, 11.5 years), median BMD z score was -0.78 SD (r ange, -3.23 to 3.61 SDs), Thirty participants (21%; 95% confidence interval , 15% to 29%) had abnormally low BMD, a proportion significantly (P < 0.000 1) greater than the expected 5% in normal populations. Risk factors for BMD decrements included male sex (P = 0.038), Caucasian race (P < 0.0001), and cranial irradiation (P = 0.0087), BMD inversely correlated with cranial ir radiation dose. BMD z scores of patients who received higher doses of antim etabolites were lower than those of other patients. Childhood ALL survivors are at risk to have low BMD, especially males, Caucasians, and those who r eceived cranial irradiation.