Peripheral Neuropathy in AL Amyloidosis: Clinical Presentations and Outcomes of Current Therapies
Pitcha Chompoopong1, Eli Muchtar2, Michelle Mauermann2
1University of Minnesota, 2Mayo Clinic
Objective:
To evaluate clinical presentations and treatment outcomes of neuropathy in AL amyloidosis.
Background:
AL amyloidosis leads to progressive and life-threatening organ failure. Systemic treatment has advanced in recent years, but neuropathy outcomes have not been studied.
Design/Methods:
We reviewed medical records of all newly diagnosed patients with AL amyloidosis seen at Mayo Clinic from 2000-2015. Peripheral neuropathy was assessed based on physical examination, Neuropathy Impairment Score (NIS), electrodiagnostic, autonomic, and thermoregulatory sweat studies.
Results:
Among 1,583 patients with AL amyloidosis, 170(10.7%) had objective evidence of neuropathy. About half (n=84, 49%) presented with length-dependent peripheral neuropathy. One quarter (n=44, 26%) had autonomic neuropathy without significant somatic symptoms. Other clinical presentations included polyradiculoneuropathy (n=32), small-fiber neuropathy (n=9), and multiple mononeuropathies (n=1). Concomitant myopathy was observed in 32(19%). Median duration of neuropathic symptoms before diagnosis was 12 months. The monoclonal light chain was lambda in 135 (79%). Neuropathy was the sole organ involved in 13(8%) patients while the rest had other organ involvements (cardiac, n=124; renal, n=80; gastrointestinal, n=39; liver, n=13). Seventy-seven patients had repeat evaluation of neuropathy at median follow-up time of 2.6 years from diagnosis; 46(60%) progressed. Stabilization of NIS and electrodiagnostic findings was observed in 19(24%) patients who received autologous stem cell therapy (ASCT, n=11), melphalan-dexamethasone (n=5), bortezomib-based regimen (n=2), and dexamethasone (n=1). Twelve(16%) patients (ASCT, n=8; melphalan-dexamethasone, n=4) had improvement in neuropathic pain, NIS, electrodiagnostic, or autonomic study findings. Median survival was 32 months. When compared to AL amyloidosis patients without neuropathy, patients with neuropathy had similar distribution of cardiac staging, but increased number of involved organs (p<0.001) and worse overall survival.
Conclusions:
Neuropathy in AL amyloidosis frequently presents with length-dependent peripheral neuropathy or autonomic neuropathy with relentless progression. However, with advances in therapeutic options, stabilization and even improvement in neuropathy can occur. Patients with neuropathy have worse survival compared to those without.