High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Rescue for Children with High-Risk Neuroblastoma. Experience of a Single Pediatric Center in Bogotá, Colombia

Abstract

Background: Iron overload has been implicated as a key co-morbid factor in post-stem cell transplant (SCT) outcomes. Quantifying iron burden has been a challenge as serum iron markers are imprecise. MRI is a relatively new and non-invasive tool that more accurately measures iron burden. We conducted a prospective study using MRI to assess iron burden in children undergoing SCT. Objective: To determine the prevalence of iron overload using R2 MRI of the liver in a pediatric allo SCT population both pre and post-SCT. Relationships between excess iron and adverse outcomes such as graft vs. host disease (GVHD), infection, and death were secondary objectives. Methods: Children $5 years old undergoing an allo SCT at Children's Hospital Boston from 2007-2009 were eligible for this study. Iron overload was defined as a liver iron concentration $ 1.5 mg iron/g dry liver tissue. A paired t-test was conducted with a 5 0.05 to compare iron load at the two specified time points. A two-sample two-sided t-test was conducted at each time point for association with risk factors described above with a 5 0.1. This study was IRB approved. Results: Twenty-eight patients were enrolled. The most common diagnoses were Pre-B ALL (N 5 7), AML (N 5 6), and aplastic anemia (N 5 5). Pre-SCT, 82% (95% CI: 66%-98%) of patients had iron overload by R2 MRI. At day 100 post-SCT, 95% (95% CI: 65%-100%) had iron overload. The mean iron concentration (6 std error) was 4.97 6 3.54 mg/g dwt liver at pre-SCT and 7.55 6 4.37 mg/ g dwt liver at day 100 post-SCT. The day 100 post-SCT mean value was significantly higher than the mean value at pre-SCT (2.15 mg/g dwt liver, p\0.0001). For patients who developed an infection during the post-SCT period, the mean iron concentration, compared to patients who did not develop an infection, was significantly higher at pre-SCT and at day 100 post-SCT (p 5 0.029 and p 5 0.0055, respectively). There was no statistically significant difference in iron concentration between patients who developed GVHD or died and those who did not. Conclusions: We found that a high proportion of pediatric allo SCT patients have iron overload pre-SCT. In addition, there is a statistically significant rise in iron post-SCT (p\0.0001) and an association with increased incidence of infection in patients with elevated iron. Larger multi-center studies should be conducted to further examine the consequences of iron overload and evaluate potential interventions in this patient population.