Bone Demineralization, Iron Overload and Time to Engraftment following Allogeneic Stem Cell Transplantation in Pediatric Patients

Background: Iron overload and osteoporosis are relatively common but often neglected complications of chemotherapy and transplantation^3,4,5. Under these pathological conditions bone marrow-derived mesenchymal stem cells (BM-MSCs) exhibited deficiencies in proliferation and imbalances in osteogenic/adipogenic differentiation, along with reduced expression of common hematopoietic cytokines chemokines and adhesion proteins². This can induce impaired production of hematopoietic progenitors and at the end compromise engraftment.

Methods: The medical records of 41 pediatric patients who underwent bone mineral density (BMD) measurement and bone iron concentration (BIC) evaluation prior to allogeneic HSCT from January 2013 to December 2016 were retrospectively reviewed. Magnetic resonance imaging was used to estimate BIC and dual-energy X-ray absorptiometry was used to measure BMD. Patients were divided into three groups, 17 with non-elevated BIC (100 μmol/g) and normal BMD (Group 2) and 10 patients with elevated BIC (>100 μmol/g) and pathological BMD at baseline. The endpoint of our study was to compare times to engraftment in the three groups.

Results: Pre-transplant BIC and BMD were significantly associated with neutrophil and platelet engraftment, with mean times to engraftment of both platelets (22.1±9.5 days vs. 42.0±35.3 and 44.6± 31.5 in three groups respectively; p<0.05) and neutrophils (17.8±4.6 days vs. 22.8± 8.8 and 23.1±10.4 days in three groups respectively, p<0.05) being significantly longer in Group 2 and 3 than in Group 1. Time to platelet engraftment showed statistically significant correlations with pre-transplant BIC (r=0.7305; p<0.001). Pre-transplant BIC also showed close correlations with mean times to neutrophil engraftment (p<0.001).

Conclusion: Our findings show a correlation between pre-transplant BIC, BMD and time to engraftment. Further studies are needed to determine whether normalization of BMD and BIC could reduce time to engraftment and therefore transplant-related morbidity and mortality.