The role of magnetic resonance imaging‐T2* in the evaluation of iron overload early in hereditary hemochromatosis. A cross‐sectional study with 159 patients

Abstract

in solid organ malignancies, including melanoma, ovarian, breast, and especially, colorectal cancers, where a higher degree of tumor-infiltrating lymphocytes (TIL) predicts improved survival independent of TNM (tumor, node, metastases) staging [1]. TIL have also shown prognostic value in various lymphoid hematological malignancies. In AML, evidence of immune modulation is seen in the "graft-versus-leukemia" effects post-allogeneic SCT together with promising preclinical activity of novel immune therapies. Furthermore, higher peripheral blood lymphocyte recovery after induction chemotherapy [2] and allogeneic SCT for AML [3] have predicted improved overall survival (OS). The prognostic significance of immune status at diagnosis has not been defined in AML. We therefore investigated whether degree of T lymphocyte infiltration within CN-AML diagnostic bone marrow trephines, which we have labeled the "leukemia-infiltrating lymphocyte" (LIL) index, had prognostic value.Patients diagnosed with CN-AML at an adult tertiary center between 2006 and 2013, treated with intensive chemotherapy and who had suitable stored, diagnostic bone marrow trephines were analyzed with institutional ethics approval. Trephines were formalinfixed, decalcified in EDTA, and processed through to paraffin. Immunostaining for pan-T cell marker, CD3, and cytotoxic markers, CD8 and Granzyme B (GB), was performed at the time of analysis using routine methods. CD4 immunostaining was attempted, however high levels of non-specific staining precluded quantitative analysis. Positive cells were quantified using FijiV C image analysis software (v1.48o) from photographs taken at 3200 magnification of three representative areas of each trephine, expressed as a percentage of total cells and averaged over the three images.The cohort included 53 patients (51% male, median age 51 years (range 19-78)) followed-up over a median of 25.9 months (range 0.17-102.6 months). Most patients (96%) had de novo AML, 47 patients (89%) achieved CR (29 (62%) of whom relapsed), 21 (40%) underwent allogeneic SCT (10 in second CR) and 20 (38%) died. From a mean of 13,768 cells per trephine analyzed, median CD3% was 4.64% (range 0.56-37.24%) (Fig. 1A,B), CD8% was 5.08% (range 0.43-43.5%) and GB% was 0.34% (range 0-10.11%). In univariate Cox regression analyses, significant risk factors for death were higher aspirate blast% (P 5 0.006), primary refractory disease (P 5 0.03), and relapse (P 5 0.04). Increasing age (P 5 0.093), FLT3-ITD positive(pos) (P 5 0.099), and CD3% (P 5 0.079) approached significance. Gender, preceding myelodysplastic syndrome, allograft, NPM1 mutation (NPM1 mut ), CD8%, and GB% were not significant. In Cox regression multivariate analyses, combining T cell numbers with the relevant univariate factors (i.e., P < 0.1), higher CD3 and CD8 were independent predictors of OS (CD3: hazard ratio (HR) 0.929 for death, 95% CI 0.870-0.992, P 5 0.029; CD8: HR 0.920, 95% CI 0.869-0.973, P 5 0.004). Patients were divided into quartiles to determine whether incremental d...

Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome

“…Several frequent conditions are associated with congenital cataract, ( 5 ) and because of that, the search for mutation in the FTL gene is rarely included in the evaluation of congenital cataract, and most patients affected by this syndrome end up being evaluated by hyperferritinemia. As mutations in the HFE gene associated with hemochromatosis are frequent in our population, ( 7 , 9 - 11 ) this is often the main presumptive diagnosis for these patients. The HFE gene is located on 6p22.2 and encodes a membrane protein that is thought to control iron absorption, by regulating the interaction of the transferrin receptor with transferrin.…”

Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect

“…MRI scan of the liver is, in the experienced setting, a good method for quantitative measurement of the liver iron content [50, 56, 57]. There exists no common consensus on the methodology, so each center has to develop its own program and calibrate their scanner using objects with known iron concentrations.…”

Hepatic iron overload identified by magnetic resonance imaging-based T2* is a predictor of non-diagnostic elastography

“…Non-invasive magnetic resonance imaging, has recently been favored as an initial diagnostic test for assessing iron overload via the parameter T2*, an exponential decay constant that can be calculated from a single gradient-echo sequence with multiple echo times. T2* sequences have demonstrated a high sensitivity in detecting hepatic as well as cardiac iron deposition, even in the early stages of the disease (11)(12)(13)(14)(15), and T2* values have been shown to correlate well with biopsy-proven liver iron concentrations (16,17). Unlike the small samples obtained from liver biopsy, T2* includes data from a large cross-section of the liver.…”