Screening practices for late effects in pediatric patients on tyrosine kinase inhibitors.

Abstract

e22527 Background: BCR-ABL tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) and chronic myeloid leukemia (CML). The off-target effects of long-term TKI use in children are poorly understood. We evaluated institutional screening practices for cardiac and endocrine late effects in those who had received TKIs at two large pediatric cancer centers. Methods: This retrospective cohort included patients diagnosed with Ph+ALL (post completion of frontline therapy) or CML at age < 21 years with ≥1 years of follow-up. Patients were censored at stem cell transplant, blast crisis, secondary neoplasm, death, or last contact. Demographics, clinical features, and incidence of screening echocardiogram (ECHO), electrocardiogram (EKG), dual-energy x-ray absorptiometry (DXA), bone age, and thyroid function (TSH) were abstracted. Descriptive statistics and incidence of screening are presented by diagnosis. Results: The cohort (n = 68) was 50% female, 28% non-Hispanic white, 24% non-Hispanic black, 24% Asian, and 19% Hispanic. CML: Patients were diagnosed at 12.9±4.6 years of age and had 6.3 (0.9-15.6) years of TKI exposure and 6.3 (0.9-15.6) years of follow-up. Imatinib was most commonly used (80%) followed by dasatinib (59%); 48% were exposed to > 1 TKI. Excluding tests at diagnosis, 48% had an ECHO and 48% had an EKG during the follow-up period. TSH, DXA and bone age were measured in 50%, 9% and 11% patients, respectively. Ph+ALL: Patients were diagnosed at 10.8±5.1 years of age and had 2.8 (0.6-11.6) years of TKI exposure and 5.7 (2.1-11.8) years of follow-up. Dasatinib was most commonly used (73%) followed by imatinib (64%); 36% were exposed to > 1 TKI. All received anthracyclines and steroids. Excluding tests at diagnosis, 91% had an ECHO and 77% had an EKG. TSH, DXA and bone age were measured in 82%, 68% and 36% patients, respectively. Conclusions: We note inconsistent cardiac and endocrine screening in patients receiving TKIs for CML and Ph+ALL. Evidence-based guidelines for long-term follow-up and structured monitoring for potential off-target effects are needed. A prospective screening study is in progress and may enhance our understanding of the prevalence of late effects of TKIs. [Table: see text]