melphalan and Amyloid-Neuropathies

Primary AL amyloid polyneuropathy (AL-PN) and neuropathy due to POEMS syndrome (POEMS-N) are rare, associated with a monoclonal gammopathy (MG) IgGλ or IgAλ at a low rate and systemic manifestations. They are invalidating and life-threatening.. AL-PN usually mimics small fiber length-dependent axonal polyneuropathies, but also multifocal or painful neuropathies, POEMS-N corresponds to a rapid ascending CIDP with MG. To confirm the diagnosis of AL-PN, initial investigations should identify amyloidosis on nerve or accessory salivary glands, to establish the type of amyloid after serum free light-chain (FLC) measurements. For the diagnosis of N-POEMS, diagnosis is based on the presence of four criteria proposed by Dispenzieri. These neuropathies are associated with biomarkers, useful for diagnosis and treatment monitoring: elevated serum level of FLC monoclonal in (AL-PN) or VEGF (N-POEMS).. Early diagnosis of these neuropathies and early treatment using high-dose melphalan associated with an autologous hematopoietic stem cell graft or low monthly doses can improve the clinical manifestations and patient survival.. Systematic search for monoclonal gammopathy by immunofixation and serum free light chains is very useful for the management of progressive peripheral neuropathies of unknown origin.

Topics: Amyloid; Amyloid Neuropathies; Biomarkers; Biopsy; Castleman Disease; Combined Modality Therapy; Drug Therapy, Combination; Early Diagnosis; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin lambda-Chains; Melphalan; Paraproteinemias; Peripheral Nerves; POEMS Syndrome; Prednisone; Salivary Glands, Minor; Skin; Thalidomide; Vascular Endothelial Growth Factor A

We report 2 patients with polyneuropathy associated with amyloid derived from light chains (AL) who were treated successfully with high-dose melphalan followed by autologous peripheral blood stem cell transplantation (HDM/SCT). Neuropathic symptoms improved in conjunction with normalization of serum-free light chains. In addition to amyloid deposits in tissues, an amyloidogenic light chain itself produced by abnormal plasma cells might be harmful to peripheral nerve function, and thus HDM/SCT seems to be a promising therapy for primary AL amyloid polyneuropathy.

Topics: Adult; Amyloid Neuropathies; Biopsy; Diagnosis, Differential; Dose-Response Relationship, Drug; Electromyography; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Muscle, Skeletal; Myeloablative Agonists; Stem Cell Transplantation; Transplantation, Autologous

Patients with AL amyloidosis can benefit from high-dose chemotherapy and autologous stem cell transplantation (ASCT). Transplantation can be challenging due to fluid shifts, sepsis, and cardiac dysrhythmias. Amyloidosis may present with autonomic neuropathy (AN) that renders peritransplant care problematic. The purpose of this study was to determine the outcome of patients with AN during and after ASCT.. We performed a case-control study of patients with AL amyloidosis with associated AN and compared them to a large matched cohort without AN who also underwent ASCT.. We identified 13 patients with AN who underwent ASCT and a matched control group of 95 patients without AN. Patients with AN had more organs involved (median 2.5 vs 1, p < 0.001) and the conditioning dose of melphalan was often reduced by 30% compared to controls without AN (p = 0.0015). Median duration of hospitalization was similar for both cohorts, as were engraftment kinetics. Atrial fibrillation occurred in all patients with AN but in only 1 control patient (p < 0.0001). Median overall survival (OS) for patients with AN was 29 months but >60 months for controls (p < 0.0001). On univariate analysis, cardiac involvement (p = 0.0132), AN (p = 0.0011), glomerular filtration rate (p = 0.038), number of organs involved (p = 0.0064), and NT-pro-BNP (p = 0.039) all had an impact on OS. On multivariate analysis, AN retained an independent adverse impact on OS.. Patients with autonomic neuropathy secondary to AL amyloidosis can undergo autologous stem cell transplantation with relative safety. Autonomic neuropathy is an independent, adverse determinant of survival in these patients.

Topics: Adult; Aged; Amyloid Neuropathies; Antineoplastic Agents, Alkylating; Autonomic Nervous System Diseases; Case-Control Studies; Chi-Square Distribution; Combined Modality Therapy; Databases, Factual; Female; Heart; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Male; Melphalan; Middle Aged; Prognosis; Statistics, Nonparametric; Transplantation Conditioning; Treatment Outcome