Quantification by Magnetic Resonance Imaging (MRI) and Consequences of Post-Transfusionnal Iron Overload in Long Bone Marrow Transplant Survivors.

Introduction The exact biological and clinical complications related to iron overload in adult non thallassemic patients receiving blood units (BU) are not well known. This is mainly due to the many confounding factors both in the evaluation of iron overload (mainly estimated by ferritin measurement) and its consequences on liver dysfunction (hepatitis, GVH) and cardiac or pancreatic function (toxicity, ageing).

Patients and Methods We prospectively evaluated biological (glycemia, liver function) and clinical (cardiomyopathy, arythmia) consequences of post-transfusionnal iron overload, as sole risk factors, in a very closely selected population of long term BM transplant survivors. We quantified liver iron content (LIC) by MRI and studied the relationship between the number of BU, LIC and liver dysfunction. Exclusion criteria were extremely strict: transplant performed after 1999, any form of GVH, hepatitis B or C, alcoholism (CAGE Questionnaire), any presence of hepatotoxic drug, requirement of BU after the one year period following transplant, inflammation, neoplastic diseases or relapse, homozygous for HFE mutation.

Results 104/150 adult patients transplanted before December 1999 were enrolled. 39/104 were excluded: GVH n=11, viral hepatitis n=3, alcoholism n=1, hepatotoxic drug n=4, active bleeding n=2, neoplastic disease or relapse n=11, chronic inflammation n=7. 65 patients were analyzed (34M,31F). Median age at transplant was 36. Median follow up was 9 years. The median number of BU received was 18 (0–77) (definitive evaluation in 60/65 patients). The median ferritin was 532 ng/ml (42–4023). 27/65 pts had AST and or ALT above normal value. Hyperlycemia was present in 11 cases. There was a significant correlation between the number of BU and the ferritin value (r= 0.81) (p<10–3) as well as between the number of BU and LIC (r=0.84)(p<10–3).38/65 patients had ferritin above normal value; among them, 31/32 cases had LIC above normal value, median 117 micromoles/gdw (30->300). The group with ferritin above normal value (n=38) differed significantly from the group with ferritin of normal range in terms of number of BU transfused (p<10 ⁻³), level of AST(p<0.017) and ALT (p<0.009). However, the risk of occurrence of liver dysfunction (AST or ALT above normal) was slightly different between the normal ferritin (8/27) and high ferritin (19/38) groups (chi 2 non-significant). In addition, in the group having received more than 20 BU (n=24) compared to the group having received less than 20 BU (n=36), there was no significant difference in the risk of occurrence of liver dysfunction but there was a significant difference between these two groups in terms of ferritin (p<10–3)(t-test) and LIC results (p=0.013)(t-test). There was no significant difference regarding glycemia. No patients had clinical cardiac disease or were arythmic.

Conclusion The magnitude of persistent iron overload in long BM transplant survivors correlates closely to the number of BU received and is well quantified by MRI. In this group having no cofactor of iron toxicity, our results suggest that the impact in the medium term of post transfusionnal iron overload on liver dysfunction, diabetes mellitus and cardiac disease is moderate.