Original Study
Clinical Characteristics and Treatment Outcome of Chinese Patients With Systemic Amyloid Light-Chain Amyloidosis: A Retrospective Single-Center Analysis

https://doi.org/10.1016/j.clml.2015.11.001Get rights and content

Abstract

Background

Amyloid light-chain (AL) amyloidosis is a disease caused by tissue deposition of light-chain proteins in vital organs that results in progressive organ damage. We analyzed the clinical characteristics of 123 AL amyloidosis patients and performed an overall survival (OS) analysis to identify critical baseline factors.

Patients and Methods

Patients (median age, 54 years) were diagnosed with organ involvement of kidney (98.4%), gastrointestinal (73%), cardiac (56%), liver (13%), or nervous system (10%), and multiorgan involvement was observed in 91% of patients. Treatment regimens of transplantation, bortezomib plus dexamethasone, melphalan plus dexamethasone, and prednisone-based regimens or no treatment resulted in 3-year OS rates of 72%, 60%, 55%, and 41%, respectively.

Results

Median OS was 38 months and was affected by age (≥ 65 years), hypoalbuminemia, renal failure, heart involvement, and organ response time (within 3 months). Multivariate analysis indicated that these were independent prognostic factors on OS except for age.

Conclusion

The AL amyloidosis patients in this study presented somewhat different features and outcomes compared to others, with younger age and higher rates of organ involvement.

Introduction

Amyloid light-chain (AL) amyloidosis is a systemic disease with deposition of misfolded protein fibrils in various tissues and organs. The amorphous amyloid fibrils are derived from monoclonal immunoglobulin light chains, which are produced by an underlying clonal plasma cell dyscrasia.1 AL amyloidosis is an uncommon disease, affecting 5 to 12 people per million per year.2 The symptoms are often nonspecific, leading to delays in diagnosis and advanced organ dysfunction when treatment is initiated. The overall prognosis of this disease is poor because accumulation of pathogenic amyloid deposits in vital tissues or organs such as the heart, kidneys, liver, gastrointestinal tract, or nerves can cause substantial morbidity and often leads to rapidly progressive organ failure and death.3, 4

Because the mechanism of the formation of amyloid fibril and organ involvement is still unclear, there is no specific therapeutic option available targeting amyloidosis. The main and direct treatment of AL amyloidosis is to suppress malignant plasma cell clones, as in multiple myeloma.5 Intensive chemotherapy regimens, including high-dose melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) and the combination of melphalan with dexamethasone (MD),6, 7, 8 have been provided to AL amyloidosis patients, resulting in significantly improved prognosis.9 Use of novel agents such as bortezomib and immunomodulatory drugs have also exhibited promising outcomes.10, 11 However, the efficacy of the various treatments is difficult to define and somewhat controversial.12 Furthermore, prognosis depend on multiple factors, such as patient age, physical conditions, and more important the severity of organ involvement and the type and number of organs already affected. Accumulation of documented clinical data from larger patient populations of different geographical regions will be beneficial for better diagnosis, prognosis evaluation, and formulating treatment regimens at treatment centers.

Currently, relevant studies of AL amyloidosis are mainly concentrated in more advanced countries in Europe and the United States. Reports on the diagnosis and therapeutics of AL amyloidosis in disadvantaged developing countries in Asia, including China, are scarce. We thus performed a retrospective analysis of 123 AL amyloidosis patients from a single center in China. We focused on clinical manifestation, disease response, and treatment outcome of AL amyloidosis. The results directly benefit current practice of AL amyloidosis diagnosis and therapies for favorable patient outcomes. Additionally the study contributes to the enlargement of existing data pool for future meta-analysis.

Section snippets

Ethical Statement

This study was approved by the Clinical Research Ethics Committee of Jinling Hospital, Nanjing, China. Written informed consent was waived by the ethics committee.

Patients and Diagnosis

The reported patient population consisted of 123 patients with AL amyloidosis admitted to the Jinling Hospital in Nanjing, China, between 2000 and 2010. AL amyloidosis was diagnosed and confirmed by biopsy in combination with clinical signs of organ involvement according to the Consensus Criteria.13 Amyloidosis of AL subtype was

Patient Characteristics

Table 1 summarizes the important patient characteristics. The median age at diagnosis was 54 years, and the median time from onset of symptoms to diagnosis was 7 months. The immunohistochemical stain identified 86 patients (84%) with λ light-chain isotype and 14 patients (14%) with κ. Types of amyloidosis in 23 cases were undetermined. The distribution of immunoglobulin heavy chains was as follows: immunofixation electrophoresis was positive in 84 cases including 6 cases of immunoglobulin (Ig)

Discussion

AL amyloidosis is the most common form of systemic amyloidosis, and it accounts for approximately 80% of all amyloidosis. The disease commonly occurs in the elderly, with a median age at onset of 62 years in Western countries.15 However, the median age of the 123 patients in our center was 54 years—8 years younger than in Western countries. This could represent a real difference, considering possible delayed diagnosis, at our center. Systemic AL amyloidosis, as a rare and severe disease, has no

Conclusion

This retrospective study reports the detailed clinical presentations of AL amyloidosis patients and their treatment outcomes in a single center of China. This group of Chinese patients was generally younger, with more male patients and more organ involvement compared to other studies. As expected, the clinical presentation, treatment selection, and outcomes were somewhat different from patient series of other countries, but factors identified as critical to prognosis were similar, such as heart

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgments

We thank all the doctors and nurses of Jinling Hospital, and in particular our many colleagues, for referring and providing clinical data. We thank all the patients who participated in this study and who sought care at our center.

References (26)

  • V. Sanchorawala

    Light-chain (AL) amyloidosis: diagnosis and treatment

    Clin J Am Soc Nephrol

    (2006)
  • R.L. Comenzo

    Amyloidosis

    Curr Treat Options Oncol

    (2006)
  • H.J. Jun et al.

    Clinical features and treatment outcome of primary systemic light-chain amyloidosis in Korea: results of multicenter analysis

    Am J Hematol

    (2013)

    • Cited by (0)

    View full text
    Copyright © 2016 Elsevier Inc. All rights reserved.