Clinical study
Stem cell transplantation for the management of primary systemic amyloidosis

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Abstract

Purpose

To review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution.

Subjects and methods

Sixty-six patients with biopsy-proven amyloidosis received transplants between March 1996 and January 2001. All patients had evidence of a clonal plasma cell dyscrasia; those with nonimmunoglobulin forms of amyloidosis were excluded, as were those who had no symptoms of amyloidosis, purpura, carpal tunnel syndrome, or symptomatic multiple myeloma.

Results

Amyloid was seen clinically in the kidneys (n = 45 patients), heart (n = 32), peripheral nerves (n = 11), and liver (n = 11). A monoclonal protein was found in the serum in 46 patients and in the urine in 57 patients. The median daily urinary protein loss was 4.1 g. Septal thickness, measured by echocardiography, ranged from 7 to 24 mm (median, 12 mm); 8 patients had a septal thickness ≥16 mm. Ten patients received transplants 1 year or more after diagnosis. All patients received melphalan-based chemotherapy; 17 patients were conditioned with total body irradiation. Nine patients required dialysis, 7 of whom died. Treatment-related mortality for stem cell transplantation was 14% (9/66). After a median of 25 months of follow-up after transplantation, the percentage of patients alive with one organ involved was 91% (31 of 34); two organs, 82% (18 of 22); three organs, 33% (3 of 9); and four organs, 0% (0 of 1). Hematologic responses were seen in 33 patients and organ responses in 32 patients. The 2-year actuarial survival of all patients was 70%.

Conclusion

The number of organs involved before stem cell transplantation for amyloidosis is the most important factor in predicting subsequent survival. Stem cell transplantation should be considered as a treatment option for selected patients with amyloidosis.

Section snippets

Methods

Amyloidosis was confirmed with a Congo red–stained tissue biopsy specimen in all patients. Patients whose disease was limited to only cutaneous involvement, purpura, or carpal tunnel syndrome were excluded. The diagnosis of light-chain amyloid required a serum or urine monoclonal light chain or the presence of clonal plasma cells in the bone marrow (5). Baseline evaluation of patients included immunofixation of serum and urine and an echocardiogram. For the purpose of counting organ

Results

We studied 66 patients who underwent transplantation between March 8, 1996, and January 17, 2001 (Table 1). All except 5 patients had evidence of an M protein in urine or serum (Table 2 ); 23 (35%) had κ light chains and 43 (65%) had λ light chains. At the time of diagnosis, signs or symptoms of amyloid were seen in the kidney in 45 patients (68%), the heart in 32 patients (48%), peripheral nerves in 11 patients (17%), the liver in 11 patients (17%), and the autonomic nervous system in 4

Discussion

Melphalan and prednisone have been used to treat amyloidosis since 1971 (10), but only a minority of patients respond, and the median survival does not exceed 2 years 11, 12. Because stem cell transplantation benefits patients with multiple myeloma (13), its use in the management of amyloidosis is logical (14). An initial report showed a clinical response in 5 patients who underwent autologous stem cell transplantation (15). With greater experience, the hematologic response rate was 62% and the

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    This study was supported in part by the Mayo Hematology Malignancies Program, Rochester, Minnesota.

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