Serum levels of free light chain before and after chemotherapy in primary systemic AL amyloidosis

Intern Med. 2005 May;44(5):428-33. doi: 10.2169/internalmedicine.44.428.

Abstract

Objective: Immunoglobulin-related free light chains (FLCs) in serum have recently become quantitatively detectable using the nephelometric assay in plasma cell disorders, including multiple myeloma and AL amyloidosis. To investigate whether FLCs are useful as a diagnostic and therapeutic marker in Japanese patients with primary systemic AL amyloidosis, we determined these values in serum before and after chemotherapy.

Patients and methods: The serum FLC analysis was carried out in 25 patients with primary systemic AL amyloidosis (mean age, 60.1+/-8.4 years). All of the patients were shown to have either ALkappa- or ALlambda-immunoreactive amyloid deposits on biopsied tissues. Thirteen patients were treated with VAD (vincristine, doxorubicin and dexamethasone) alone (n=6) or VAD and subsequent high-dose melphalan followed by autologous stem cell support (n=7), and serum FLCs were serially determined before and after the chemotherapy.

Results: Before chemotherapy the amyloidogenic FLC was elevated in serum with or without abnormal e/e ratios in 24 patients, including 5 with undetectable M-protein in both serum and urine on immunofixation. After chemotherapy the amyloidogenic FLC in serum was significantly decreased irrespective of high-dose melphalan (p<0.05), and all the patients with normalized kappa/lambda ratios showed a good prognosis.

Conclusions: With respect to sensitivity and quantification serum FLCs will be a key marker for diagnosis and therapeutic effects in primary systemic AL amyloidosis. The prognosis of patients with this disease may be improved if the kappa/lambda ratio in serum can be normalized by intensive chemotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyloidosis / blood*
  • Amyloidosis / pathology
  • Amyloidosis / therapy
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers / blood
  • Biopsy
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Immunoassay
  • Immunoglobulin Light Chains / blood*
  • Immunoglobulin kappa-Chains / blood
  • Immunoglobulin lambda-Chains / blood
  • Incidence
  • Infusions, Intravenous
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Japan / epidemiology
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Melphalan / administration & dosage
  • Melphalan / therapeutic use*
  • Middle Aged
  • Myeloma Proteins / metabolism
  • Nephelometry and Turbidimetry
  • Peripheral Blood Stem Cell Transplantation
  • Retrospective Studies
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / therapeutic use

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers
  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Myeloma Proteins
  • multiple myeloma M-proteins
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Melphalan

Supplementary concepts

  • VAD protocol