Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only.

PURPOSE: A clinical trial designed to test whether treatment with melphalan, prednisone, and colchicine (MPC) is superior to colchicine (C) alone was performed in patients with primary amyloidosis (AL), a nonmalignant plasma cell dyscrasia. PATIENTS AND METHODS: Patients were randomized to MPC or C with stratification according to sex, time from diagnosis to study entry (ie, less than 3 months or 3 to 12 months), and dominant organ system involvement (ie, cardiac, renal, neurologic, or others). Data were gathered monthly from patients, quarterly from physicians, and annually in the Clinical Research Center. One hundred consecutive patients with AL amyloidosis admitted between 1987 and 1992 who met eligibility requirements were treated and followed for a minimum of 18 months. Fifty patients (group A) received daily oral colchicine and 50 patients (group B) received cycles of oral melphalan and prednisone every 6 weeks for 1 year as well as colchicine. RESULTS: The principal outcome measure was median survival, which was compared in the two treatment groups and in the subgroups. The overall survival of all patients from study entry was 8.4 months. Comparing group A (C) to group B (MPC), the survival was 6.7 months versus 12.2 months (P = 0.087). Both treatment groups had poor survival for patients in the cardiac subgroup, longest survival in the renal group, and significant differences favoring MPC treatment only in patients whose major system manifestations were neurologic (P = 0.037) or other (P = 0.007). Multivariate analysis showed a strongly significant treatment effect (P = 0.003) and improved survival associated with not having cardiac or gastrointestinal involvement. CONCLUSIONS: MPC was advantageous for patients whose major manifestations of amyloid disease were other than cardiac or renal. Better survival regardless of treatment was noted in patients for whom a satisfactory supportive treatment such as transplant or dialysis exists for their organ failure.

Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973).

Primary amyloidosis has a variable course, but is generally associated with a short life expectancy. To date, no specific therapy has been available. Fifty-three patients with AL amyloidosis seen between 1976 and 1983 were treated with colchicine, and their clinical course and survival were compared with that in 29 other patients seen between 1961 and 1973. Of the variables measured, the treatment, the patient's sex, and the time interval from diagnosis to referral of treatment were significantly associated with length of survival. Median survival for the colchicine-treated patients was 17 months, compared with six months for the non-colchicine-treated patients. A surprising finding was the longer life span in female patients (median eight months versus four and a half months in the non-colchicine-treated group, and 25.5 months versus 10 month in the colchicine-treated group). The study suggests that colchicine has improved the life expectancy in AL amyloidosis. Although it is not a specific therapy, it may be a reasonable form of adjunctive treatment in this complex disorder.

Lowered prealbumin levels in patients with familial amyloid polyneuropathy (FAP) and their non-affected but at risk relatives.

Amyloid fibrils in familial amyloid polyneuropathy, the familial (AF) form of systemic amyloidosis, are composed of the monomeric unit (14,000 MW) of prealbumin molecules. By radioimmunoassay, the serum level of prealbumin was measured in 25 patients from 12 different kinships with this dominantly inherited form of amyloidosis and 56 unaffected, but at risk, relatives from two of the kinships. Results were compared to prealbumin levels in normal individuals and patients with primary (AL) and secondary (AA) forms of systemic amyloidosis. Significantly lowered prealbumin levels were found in the AF patients (149.2 micrograms/ml) and their at risk relatives (169.0 micrograms/ml) when compared to normal individuals (232.9 micrograms/ml), AL patients (221.9 micrograms/ml) and AA patients (211.7 micrograms/ml). No abnormality was found in levels of retinol binding protein (RBP), which is carried by prealbumin, in the serum of either the AF patients or their relatives. The depressed prealbumin levels may indicate a structural variant molecular form, an extra hepatic synthesis or an abnormality in catabolism of this protein that is present prior to the clinical or histopathologic onset of the AF disease.

Familial amyloid polyneuropathy. Demonstration of prealbumin in a kinship of German/English ancestry with onset in the seventh decade.

A family with autosomal dominant transmitted familial amyloid polyneuropathy residing in Texas is described. Clinically, the prominent sensory and severe autonomic nervous system involvement resembles the Andrade (Portuguese) type I familial amyloid polyneuropathy but is unique in that the age of onset is in the seventh decade in all family members affected to date. Using an immunoperoxidase technique, prealbumin was demonstrated in the amyloid deposits. This finding suggests that this family shares biochemical as well as clinical characteristics consistent with similar kinships with type I familial amyloid polyneuropathy of diverse geographic origin.

Use of abdominal fat tissue aspirate in the diagnosis of systemic amyloidosis.

The needle aspirate of abdominal fat was investigated for its sensitivity in giving a tissue diagnosis in 32 consecutive patients with systemic amyloidosis. The fat tissue aspirate was stained with Congo red and examined with a polarizing microscope. Positive results were obtained in 95% (18/19) of patients with primary (AL) amyloidosis, 66% (4/6) of patients with secondary (AA) amyloidosis, and 86% (6/7) of patients with the heredofamilial (AF) form. The overall positive yield was 88% (28/32). Abdominal fat tissue aspiration is proposed as a simple, rapid, and effective technique for the diagnosis of amyloidosis. The prevalence of positive results in known amyloid disease are comparable with the rectal biopsy specimen and are more frequent than gingival or skin biopsy specimens.

Juvenile rheumatoid arthritis with renal amyloidosis: a 23-year survival.

A 14-year-old girl with juvenile rheumatoid arthritis developed severe renal amyloidosis and presented with nephrosis and renal failure. Renal function returned to normal in a year and over 23 years, serial biopsies showed remarkable, biopsy-proven regression of amyloid deposits. Amyloid was not found in skin, gum or rectal biopsies. This case demonstrates an improved prognosis and apparent reversibility.