Rochester, MN, USA
NOTE: THE AUDIO FOR THIS PRESENTATION IS NOT AVAILABLE DUE TO TECHNICAL PROBLEMS WITH THE RECORDING.
Light chain deposition disease (LCDD) is a plasma cell dyscrasia characterized by non-amyloid deposits in various organs. It is the most common form of monoclonal immunoglobulin deposition disease which includes light heavy chain deposition disease (LHCDD) and heavy chain deposition disease (HCDD). Light chain deposition disease was first described by Randall et al. in 1976 but non-amyloidotic kidney disease resembling diabetes had been reported since the 1950’s.(1)
The true incidence of LCDD is unknown. Autopsy data of myeloma patients suggest the rate of LCDD is approximately 5%.(2) This is compared to 9% for AL amyloidosis and 32% for cast nephropathy in the same study. The rate appears to be much higher amongst patients with a monoclonal gammopathy who underwent a kidney biopsy. In this study, LCDD was found in 11.6% and LHCDD in 4.1%.(3) Rates of cast nephropathy and AL amyloidosis were found in only 10.7% of the patients.
Light chain deposition disease occurs in the sixth decade of life. The age however ranges from 28 to 94 years.(4) There may be a slightly higher incidence in males. Nearly every patient presents with renal manifestations. This includes renal insufficiency, proteinuria and hypertension. Extrarenal manifestation occurs in about 35% of the patients. Nearly every organ can be involved with the most commonly reported being the heart and liver. Lung, gut, peripheral nerves, autonomic nervous system, muscle, salivary gland, carpel tunnel and brain may become involved.(5)
There is a definite predilection for kappa light chain in LCDD. Nearly 74% of patients with LCDD have a monoclonal kappa light chain. Proportion may be higher in smaller series. There also appears to be an overrepresentation of the κI subtype in this disease. Protein analysis revealed in increased hydrophobicity in these light chains.(6) One study suggests the mutations are at the somatic level and appears to be concentrated in the CDR regions of the gene.
Many patients with LCDD also have multiple myeloma. The rate of myeloma varies from 37% to 65%.(4,7) This variation may explain the differences in life expectancy reported in these patients in the literature. The median survival varies from 18 months to over 5 years. The myeloma rate in the study with the longest survival was 37% compared with over 50% in studies with shorter median survivals. However, another study suggests the histologic pattern may be more important in determining survival. In this study, the presence of myeloma did not affect survival but patients who had LHCDD had a significantly shorter survival.(8)
There is a great variation in the treatment of LCDD. Some patients with renal limited disease without myeloma may not receive any disease directed therapy. Others are given steroids and cytotoxic agents similar to those used in the treatment of multiple myeloma with varying success. One study suggests those who received vincristine-doxorubicin-dexamethasone/ methylprednisolone may have a better outcome. These patients were also more likely to have multiple myeloma.4
High dose melphalan with stem cell rescue has also been used in these patients. The experience has been small but so far appears to be beneficial with a low treatment mortality rate. Royer et al reported their experience with 11 patients, 10 of whom had multiple myeloma.(9) After stem cell transplant, 6 patients achieved hematologic complete response and 2 had very good partial response. Responders were also noted to have organ response including improvement in heart, liver and kidney function. Three patients relapsed after stem cell transplant and 1 died as a result of progressive myeloma. Boston University reported their experience with stem cell transplant in 6 LCDD patients without myeloma.(10) Complete hematologic response was achieved in 86%. All had normalized their serum free light chain levels. All were alive at a median follow-up of 12 months. It appears that high dose melphalan followed by autologous stem cell transplant may be the treatment of choice for these patients regardless of their myeloma status. It provides the patient with the highest chance of achieving hematologic CR with a low treatment related mortality rate.
1. Randall RE, Williamson WC, Jr., Mullinax F, Tung MY, Still WJ. Manifestations of systemic light chain deposition. American Journal of Medicine. 1976;60:293-299.
2. Ivanyi B. Renal complications in multiple myeloma. Acta Morphologica Hungarica. 1989;37:235-243.
3. Paueksakon P, Revelo MP, Horn RG, Shappell S, Fogo AB. Monoclonal gammopathy: significance and possible causality in renal disease. American Journal of Kidney Diseases. 2003;42:87-95.
4. Pozzi C, D'Amico M, Fogazzi GB, et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. American Journal of Kidney Diseases. 2003;42:1154-1163.
5. Buxbaum J, Gallo G. Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases. Hematology - Oncology Clinics of North America. 1999;13:1235-1248.
6. Vidal R, Goni F, Stevens F, et al. Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: potential effects on aberrant protein conformation and deposition. American Journal of Pathology. 1999;155:2009-2017.
7. Heilman RL, Velosa JA, Holley KE, Offord KP, Kyle RA. Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. American Journal of Kidney Diseases. 1992;20:34-41.
8. Lin J, Markowitz GS, Valeri AM, et al. Renal monoclonal immunoglobulin deposition disease: the disease spectrum. Journal of the American Society of Nephrology. 2001;12:1482-1492.
9. Royer B, Arnulf B, Martinez F, et al. High dose chemotherapy in light chain or light and heavy chain deposition disease. Kidney International. 2004;65:642-648.
10. Weichman K, Dember LM, Prokaeva T, et al. Clinical and molecular characteristics of patients with non-amyloid light chain deposition disorders, and outcome following treatment with high-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplantation. 2006;38:339-343.