Current issues of ACP Journal Club are published in Annals of Internal Medicine


Prognosis

Predicting survival in primary amyloidosis

ACP J Club. 1991 Mar-April;114:59. doi:10.7326/ACPJC-1991-114-2-059


Source Citation

Gertz MA, Kyle RA, Greipp PR, Katzmann JA, O'Fallon WM. Beta2-microglobulin predicts survival in primary systemic amyloidosis. Am J Med. 1990;89:609-14. [PubMed ID: 2239980]


Abstract

Objective

To assess whether β2-microglobulin levels predict survival or response to therapy in patients with primary systemic amyloidosis without associated multiple myeloma.

Design

Inception cohort of untreated patients assembled as part of 2 sequential studies of therapy.

Setting

A tertiary care center at the Mayo Clinic, Rochester, Minnesota.

Patients

The study sample comprised 153 patients with biopsy-proven, previously untreated, primary systemic amyloidosis. Patients were excluded because of overt multiple myeloma; senile, secondary, familial, or localized amyloidosis; or the carpal tunnel syndrome as their only manifestation of primary amyloidosis.

Assessment of prognostic factors

Serum β2-microglobulin estimations were available in 131 patients at presentation. All patients were followed until death or for a minimum of 8 years. Normal was defined as ≤ 2.7 mg/mL.

Main results

The median survival of the entire group was 21.1 months; the 1-, 3-, and 5-year survival rates were 63%, 34%, and 20%, respectively. The median survival of patients with increased β2-microglobulin levels was 10.8 months compared with 32.9 months in those with normal β2-microglobulin levels (P < 0.001). When the analysis was restricted to patients with normal renal function, the median survival for elevated β2-microglobulin level and normal level were 9.1 months and 39.4 months, respectively (P < 0.001). Using a multivariate proportional- hazards statistical model, congestive cardiac failure (P < 0.001) and elevated β2-micro- globulin levels (P = 0.05) were associated with poor outcomes. After adjustment for the presence of cardiac failure, β2-microglobulin levels remained significant. There was no association of β2-micro- globulin with response to therapy or with the type of urinary light chain.

Conclusion

The serum β2-microglobulin level appears to offer a useful way of identifying a subset of patients with primary amyloidosis with unfavorable outcomes.

Source of funding: In part, the Quade Amyloidosis Research Fund, Mayo Foundation.

Address for article reprint: Dr. M. Gertz, Dysproteinemia Clinic, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.


Commentary

Gertz and colleagues are experts in the field of dysproteinemias, and work in a tertiary care center that has provided important information about primary amyloidosis for over 10 years. Included in this work has been the difficult but fruitful delineation of variables that indicate prognosis among patients with plasma cell dyscrasias, which has contributed in particular to a better staging of multiple myeloma with the use of the β2-microglobulin (1).

Primary systemic amyloidosis is a plasma cell dyscrasia that shares many features with multiple myeloma. This investigation used methods from the authors' previous work with multiple myeloma to select an inception cohort of patients with primary systemic amyloidosis and to clarify subsets of patients using β2-microglobulin. The patients were carefully characterized, with their diagnosis confirmed by biopsy, and were all followed for at least 8 years. Although the inception cohort was taken from 2 separate studies, the selection criteria were constant, and no significant difference occured in survival between treatment groups.

The results support the value of β2-microglobulin as an independent indicator of prognosis for patients with primary systemic amyloidosis. Unfortunately, further work is needed to find indicators of response to therapy, as neither β2-microglobulin nor any of the other factors that were studied predicted this.

Salvatore J. Scialla, MD
Hematology and Oncology Associates of Northeastern PAScranton, Pennsylvania, USA


Commentary Addendum

More recently, Kyle and colleagues have published a long-term survival study based on the Mayo experience suggesting that congestive heart failure, older age, renal insufficiency, bone marrow plasmacytosis >20%, platelet count of <109/L, and peripheral neuropathy are unfavorable prognostic feature (2). Furthermore, currently available therapies unfortunately do not seem to be able to reverse the poor prognosis (3, 4).


Reference

1. Greipp PR, Katzmann JA, O'Fallon WM, Kyle RA. Value of β2 microglobulin level and plasma cell labeling indices as prognostic factors in patients with newly diagnosed myeloma. Blood. 1988;72:219-23.

2. Kyle RA, Gertz MA, Greipp PR, et al. Long-term survival (10 years or more) in 30 patients with primary amyloidosis. Blood. 1999;93:1062-6.

3. Kyle RA. High-dose therapy in multiple myeloma and primary amyloidosis: an overview. Semin Oncol. 1999;26:74-83.

4. Gertz MA, Lacy MQ, Lust JA, et al. Prospective randomized trial of melphalan and prednisone versus vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis. J Clin Oncol. 1999;17:262-7.