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


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.
Matsuda
Masayuki
M
Third Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Yamada
Toshiyuki
T
Gono
Takahisa
T
Shimojima
Yasuhiro
Y
Ishii
Wataru
W
Fushimi
Tomohisa
T
Sakashita
Kazuo
K
Koike
Kenichi
K
Ikeda
Shu-ichi
S
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000097:blood* / Q000473:pathology / Q000628:therapy; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007118:Immunoassay; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D015994:Incidence; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009194:Myeloma Proteins / Q000378:metabolism; D009391:Nephelometry and Turbidimetry; D036102:Peripheral Blood Stem Cell Transplantation; D012189:Retrospective Studies; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D008558:Melphalan