Iron overload in allogeneic hematopoietic cell transplantation outcome: a meta-analysis.

An elevated ferritin level before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and nonrelapse mortality. Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC > 7 mg/g dry weight (primary endpoint) was 1.4 (P = .18). In contrast, ferritin >1000 ng/mL was a significant prognostic factor (HR for mortality, 1.7; P = .036). There was, however, no significant association between ferritin > 2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT.

Prognostic impact of pretransplant iron overload measured with magnetic resonance imaging on severe infections in allogeneic stem cell transplantation.

OBJECTIVE: Infections and graft-versus-host disease (GVHD) are the main causes of transplant-related mortality (TRM) of patients undergoing allo-SCT. The role of iron overload (IO) has been debated in this context. Studies, performed with non-specific surrogate markers of iron, suggest that IO predicts poor outcome after allo-SCT. METHODS: In this prospective study, we quantified pretransplant IO with MRI-based hepatic iron concentration (HIC) measurement; the degree of IO was used to predict infections, GVHD, and mortality after allo-SCT. Logistic univariate, multivariate, and Cox's regression analyses were performed. RESULTS: Iron overload was present in 78% of the patients (HIC>36 µmol/g). The median HIC was 98 µmol/g (range 5-348). There were no cases of cardiac iron excess. IO was significantly associated with severe infections during the early post-transplant period (for every 10 µmol/g increase OR: 1.15, 95% CI 1.05-1.26, P = 0.003). The odds for severe infections increased 6.5- (>125 µmol/g OR: 6.5, P = 0.013) to 14-fold (>269 µmol/g OR: 14.1, P = 0.040) with increasing HIC. IO was found to be associated with reduced risk of acute and chronic GVHD. Although TRM was due to infection-related deaths, IO was not associated with TRM or OS. CONCLUSION: Pretransplant IO, measured with a direct MRI-based measurement, predicts severe infections in the early post-transplant period.

Fractional anisotropy and mean diffusivity parameters of the brain white matter tracts in preterm infants: reproducibility of region-of-interest measurements.

BACKGROUND: Diffusion tensor parameters can be analysed by fitting regions of interest (ROIs) to selected brain structures. The clinical usefulness of these measurements is influenced by their reproducibility and validity. OBJECTIVE: To investigate the reproducibility of fractional anisotropy (FA) and mean diffusivity (MD) measurements. MATERIAL AND METHODS: Seventy-six infants were imaged once at term-equivalent age. We measured several brain regions. Reproducibility was assessed using intraclass correlation coefficient and Bland-Altman method. RESULTS: Intra-observer reproducibility was excellent for FA in the calcarine cortex (right) and frontal white matter (left), and for MD in the corpus callosum (anterior), internal capsule, corona radiata, putamen, frontal white matter, optic radiation (left), thalamus (right) and calcarine cortex (right). Inter-observer reproducibility was excellent for FA in the corpus callosum (posterior) and for MD in the internal capsule and corona radiata (right). Inter-observer reproducibility was poor for FA in frontal and posterior white matter (right) and for MD in the inferior colliculus (right). Reproducibility was fair to good in other areas. The Bland-Altman plots showed no considerable bias, and variance was independent of the mean value. CONCLUSION: Reproducibility of ROI measurement was fair to good for both FA and MD.

Quantitative liver iron measurement by magnetic resonance imaging: in vitro and in vivo assessment of the liver to muscle signal intensity and the R2* methods.

PURPOSE: To evaluate the liver-to-muscle signal intensity and R2* methods to gain a transferable, clinical application for liver iron measurement. MATERIALS AND METHODS: Sixteen liver phantoms and 33 human subjects were examined using three 1.5-T MRI scanners from two different vendors. Phantom-to-muscle and liver-to-muscle signal intensity ratios were analyzed to determine MRI estimated phantom and hepatic iron concentration (M-PIC and M-HIC, respectively). R2* was calculated for the phantoms and the liver of human subjects. Seven patients' biochemical hepatic iron concentration was obtained. RESULTS: M-PIC and R2* results of three scanners correlated linearly to phantom iron concentrations (r=0.984 to 0.989 and r=0.972 to 0.981, respectively), and no significant difference between the scanners was found (P=.482 and P=.846, respectively) in vitro. The patients' R2* correlated linearly to M-HIC of the standard scanner (r=0.981). M-HIC values did not differ from those obtained from the biopsy specimens (P=.230). The difference in M-HIC was significant, but the difference in R2* was not significant between the scanners (P<.0001 and P=.505, respectively) in vivo. CONCLUSION: Both methods, M-HIC and R2*, are reliable iron concentration indicators with linear dependence on iron concentration in vivo and in vitro. The R2* method was found to be comparable among different scanners. Transferability testing is needed for the use of the methods at various scanners.

Functional evaluation of microvascular free flaps with positron emission tomography.

BACKGROUND: The aim of this study was to assess blood flow (BF) of microvascular free flaps studied with positron emission tomography (PET) in patients with head and neck squamous cell cancer (HNSCC) undergoing major radical surgery 3-4 weeks after high-dose radiotherapy. METHODS: Five patients underwent resection of the HNSCC of the oral cavity followed by microvascular reconstruction with a radial forearm flap. Regional BF in oral and neck tissues was measured with PET using radiolabelled water ([15O]H2O) twice (1-2 and 12-14 days, respectively) following radical surgery. RESULTS: In the first postoperative PET study, the median BF in the cutaneous flap area was 5.1 mL/100 g/min, and in the muscle contra-lateral to the recipient site 19.9 mL/100 g/min. A low flap-to-muscle BF ratio appeared to correlate with circulatory incongruity, and thus with poorer flap success. The follow-up study on the second postoperative week supported the results of the primary PET scan. CONCLUSIONS: This pilot study suggests that PET using [15O]H2O is a feasible method to quantitatively evaluate BF of the whole free flap in patients operated on for oral