Management of Patients With Erythropoietic Protoporphyria-Related Progressive Liver Disease.

Erythropoietic protoporphyria (EPP) is an inherited metabolic disorder of heme synthesis resulting from overproduction of protoporphyrin IX (PPIX), which can lead to progressive liver disease characterized by recurrent EPP crises and end-stage liver disease. We used the Australian Transplant Registry to identify 5 patients referred for liver transplantation between 2008 and 2017. A total of 4 patients had EPP secondary to ferrochelatase deficiency, and 1 patient had X-linked EPP. No patient had follow-up with a specialist prior to the diagnosis of progressive liver disease. There were 3 patients who underwent orthotopic liver transplantation, whereas 2 died while on the transplant waiting list. Parenteral PPIX-lowering therapy was used in 4 patients and was effective in 3 patients, although 2 of these had rebound porphyria and worsening liver function following a decrease in the intensity of therapy. Early disease recurrence in the allograft following transplantation occurred in 2 patients requiring red cell exchange (RCE) to successfully attain and maintain low PPIX levels, but RCE was associated with hemosiderosis in 1 patient. Allogeneic stem cell transplantation (AlloSCT) was performed in 2 patients. One failed engraftment twice, whereas the second rejected the first graft but achieved full donor chimerism with a second graft and increased immunosuppression. In conclusion, our observations suggest that progressive liver disease needs parenteral PPIX-lowering treatment with the intensity adjusted to achieve a target Erc-PPIX level. Because EPP liver disease is universally recurrent, AlloSCT should be considered in all patients with adequate immunosuppression to facilitate engraftment. RCE appears to be effective for recurrent EPP liver disease but is associated with an increased risk of iron overload.

Combination bone marrow imaging using positron emission tomography (PET)-MRI in plasma cell dyscrasias: correlation with prognostic laboratory values and clinicopathological diagnosis.

OBJECTIVE: This prospective observational study of positron emission tomography (PET)-MRI findings in 16 consecutive newly diagnosed patients with a plasma cell dyscrasia describes and compares MRI-detected myeloma lesions with 18F-fludeoxyglucose PET-avid myeloma lesions, and correlates quantitative imaging findings to a range of biochemical and prognostic parameters. METHODS: Simultaneously acquired whole body PET and MRI images were evaluated qualitatively for the presence of focal or generalised abnormalities of bone marrow (BM) on either modality. Quantitative analysis comprised mean standardised uptake values (SUVmean) and fractional water content of the BM measured from PET and chemical shift MRI images of the second to fourth lumbar vertebrae. RESULTS: Final diagnoses comprised symptomatic myeloma (n = 10), asymptomatic myeloma (n = 4) and monoclonal gammopathy of uncertain significance (n = 2). 8/10 patients with symptomatic myeloma demonstrated BM abnormalities on qualitative assessment of MRI compared to 4/10 on PET. BM SUVmean inversely correlated with serum albumin (r = 0.57, p = 0.017). BM water fraction correlated with trephine cellularity and blood platelet count (r = 0.78, p = 0.00039 and r = 0.61, p = 0.0013 respectively). BM water fraction correlated with SUVmean in patients with low plasma cell burden (r = 0.91, p = 0.0015) but not in patients with high plasma cell burden (r = 0.18, p = 0.61). CONCLUSION: PET-MRI shows promise in both morphological and functional multiparametric quantitative assessment of myeloma. ADVANCES IN KNOWLEDGE: For the first time, multiparametric imaging in myeloma has been shown to predict BM abnormalities and correlate with known biochemical prognostic markers, moving PET-MRI beyond simple diagnostic applications into potential prognostic and treatment selection applications.