Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation

Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranulom

Sex differences in wild-type transthyretin amyloidosis: An analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive disease resulting from the accumulation of wild-type transthyretin (TTR) amyloid fibrils, and is diagnosed primarily in males. This analysis examined sex differences in patients with ATTRwt amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). METHODS: THAOS is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of TTR mutations. THAOS data were analyzed to identify potential differences in demographic and clinical characteristics between males and females with ATTRwt amyloidosis (data cutoff: August 1, 2021). RESULTS: Of 1386 patients with ATTRwt amyloidosis, 84 (6%) were female and 1302 (94%) were male. Females had a higher median age at enrollment (80 vs. 78 years; p = 0.002) and symptom onset (75 vs. 73 years; p = 0.045) than males. Mean left ventricular (LV) ejection fraction was higher (53% vs. 48%; p = 0.001) and mean LV diastolic diameter lower (42 vs. 46 mm; p \u3c 0.001) in females versus males, but sex was not identified as a predictor of LV mean wall thickness adjusted for height (beta coefficient - 0.22; p = 0.460) or a predominantly cardiac phenotype (odds ratio 1.60; p = 0.191). Modified polyneuropathy disability scores differed between groups (p \u3c 0.001), with a larger proportion of scores ≥ IIIa among females (23% vs. 7%). CONCLUSIONS: Females with ATTRwt amyloidosis in THAOS tended to present at a later age and showed signs of less severe cardiac impairment and more severe walking impairment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00628745

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS):14-year update

Abstract Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.http://deepblue.lib.umich.edu/bitstream/2027.42/173793/1/13023_2022_Article_2359.pd

Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice

Patient-reported outcomes in AL amyloidosis have not been well-studied. We analyzed health-related quality of life (HRQOL) and AL amyloidosis symptoms data from the phase 3 TOURMALINE-AL1 trial (NCT01659658) (ixazomib-dexamethasone, n = 85; physician's choice of chemotherapy [PC], n = 83). HRQOL and symptom burden were measured with the SF-36v2, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG-Ntx), and an amyloidosis symptom questionnaire (ASQ). Score changes during treatment were analyzed descriptively and using repeated-measures linear mixed models; analyses were not adjusted for multiplicity. Least-squares (LS) mean changes from baseline were significantly higher (better HRQOL) for ixazomib-dexamethasone at several cycles for SF-36v2 Role Physical and Vitality subscales (p <.05); no subscales demonstrated significant differences favoring PC. For FACT/GOG-Ntx, small but significant differences in LS mean changes favored ixazomib-dexamethasone over PC at multiple cycles for seven items and both summary scores; significant differences favored PC for one item (trouble hearing) at multiple cycles. ASQ total score trended downward (lower burden) in both arms; significant LS mean differences favored ixazomib-dexamethasone over PC at some cycles (p <.05). Patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone experienced HRQOL and symptoms that were similar to or trended better than patients treated with PC despite longer duration of therapy

Prognosis of Transthyretin Cardiac Amyloidosis Without Heart Failure Symptoms.

BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. OBJECTIVES The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. METHODS Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. RESULTS A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). CONCLUSIONS After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.This work was supported by grants from Instituto de Salud Carlos III (PI18/0765 and PI20/01379). Dr Gonzalez-Lopez has received speaker fees from Pfizer and Alnylam; has received consulting fees from Pfizer and Proclara; and has received research and educational support to her institution from Pfizer, BridgeBio, and Alnylam. Dr Obici has received speaker and consulting fees from Pfizer, Alnylam, and Akcea. Dr AbouEzzeddine has received research grant support from Pfizer. Dr Mussinelli has received speaker fees from Pfizer and Akcea. Dr Dispenzieri has received consulting fees from Janssen and Akcea; and has received research support from Pfizer, Alnylam, Celgene, and Takeda. Dr Perlini has received speaker and consulting fees from Pfizer, Alnylam, and Akcea. Dr Palladini has received speaker fees from Janssen-Cilag, Pfizer, and Siemens; and has participated on an advisory board for Janssen Cilag. Dr Damy has received research grants or consulting fees from Alnylam, Akcea, Pfizer, and Prothena. Dr Grogan has received research grant support and consulting fees to her institution from Alnylam, Eidos, Pfizer, and Prothena. Dr Maurer has received grant support from National Institutes of Health (R01HL139671-01, R21AG058348, and K24AG036778); has received consulting income from Pfizer, GlaxoSmithKline, Eidos, Prothena, Akcea, and Alnylam; and has received clinical trial funding to his institution from Pfizer, Prothena, Eidos, and Alnylam. Dr Garcia-Pavia has received speaker fees from Pfizer, BridgeBio, Alnylam, and Ionis; has received consulting fees from Pfizer, BridgeBio, AstraZeneca, NovoNordisk, Neuroimmune, Alnylam, Alexion, and Attralus; and has received research and educational support to his institution from Pfizer, BridgeBio, and Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S