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. Sattianayagam PT, Gibbs SDJ, Rowczenio D, Pinney JH, Wechalekar AD, Gilbertson JA, Hawkins PN, Lachmann HJ, Gillmore JD (University College London Medical School, London, UK). Hereditary lysozyme amyloidosis - phenotypic heterogeneity and the role of solid organ transplantation. J Intern Med 2012; 272: 36-44. Objectives. Lysozyme amyloidosis (ALys) is a form of hereditary systemic non-neuropathic amyloidosis, which is inherited in an autosomal dominant fashion. Lysozyme, which is the amyloidogenic precursor protein in ALys, is a ubiquitous bacteriolytic enzyme synthesized by hepatocytes, polymorphs and macrophages. The aim of this study is to describe the phenotype and outcome of patients with ALys including the role of solid organ transplantation. Design. Retrospective evaluation of patients with ALys. Setting. UK National Amyloidosis Centre. Patients. All 16 patients with ALys followed at the centre. Results. A family history of amyloidosis was present in every affected individual. Although the phenotype was broadly similar amongst those from the same kindred, there were marked phenotypic differences between kindreds who possessed the same amyloidogenic mutation. Symptomatic gastrointestinal (GI) amyloid was prevalent, and macroscopically visible amyloidotic lesions were present in nine of 10 patients who underwent GI endoscopy. All symptomatic ALys individuals had hepatic amyloid. Four patients received orthotopic liver transplants (OLT), three for spontaneous hepatic rupture and one case, who had extensive hepatic amyloid and a strong family history of hepatic rupture, pre-emptively. All of the liver grafts were functioning at censor 1.7, 5.8, 9.0 and 11.0 years after OLT. Five patients had progressive amyloidotic renal dysfunction culminating in end-stage renal failure, three of whom underwent renal transplantation (RTx). There was no evidence of renal allograft dysfunction at censor 6.6, 1.8 and 0.8 years after RTx. Conclusions. Lysozyme amyloidosis is a disease of the GI tract, liver and kidneys, which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid-specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end-stage renal disease, respectively, with excellent outcomes in terms of medium-term graft function and patient survival. [ABSTRACT FROM AUTHOR]

BACKGROUND Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition ofamyloid fibrils oflight chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage ofpatients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53 . 3 % vs. 18.1%) (relative risk ratio, 2.9; 9596 confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P=0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.90/0, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7,8% and 4.30/0, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7°/0). Systemic administration-related reactions to daratumumab occurred in 7.3% ofthe patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression, (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.) [ABSTRACT FROM AUTHOR]