The objective of this study was to review (1) the factors that have been linked to prediction of clinical outcome and survival in amyloidosis and (2) the available studies on the therapy for localized and systemic forms of amyloidosis. We made a retrospective review of the relevant literature on treatment and prognosis in localized and systemic amyloidosis dating back to 1975. The most important prognostic factors in amyloidosis are the presence of congestive heart failure, beta 2-microglobulin, and whether peripheral neuropathy dominates the presentation. The presence of a monoclonal light chain in serum or urine, multiple myeloma, and hepatic involvement are also important adverse factors. Colchicine is beneficial in treating familial Mediterranean fever and may play a role in managing secondary amyloidosis in inflammatory bowel disease. Chlorambucil is particularly useful in juvenile rheumatoid arthritis with amyloidosis. Dimethyl sulfoxide provides benefit in bladder and lichen amyloidosis. A trial of alkylating agent-based chemotherapy is reasonable in symptomatic primary systemic amyloidosis. Advances have been made in the treatment of amyloidosis and include chemotherapy, dialysis, transplantation, and improved supportive care. Definite disease regressions with long-term survival (> 10 years) are seen. Unfortunately, alternatives still need to be developed: Of 859 patients with primary systemic amyloidosis seen at the Mayo Clinic from 1982 to 1992, the median survival was 2.1 years.

Amyloidosis↗

PubMed1994

Detection of peripheral blood plasma cells as a predictor of disease course in patients with smouldering multiple myeloma.

We evaluated the number and labelling index of circulating peripheral blood monoclonal plasma cells (PBPC) in 57 patients with newly diagnosed smouldering multiple myeloma (SMM) to determine if these measurements could distinguish SMM from active multiple myeloma (MM). The PBPC were detected by a sensitive slide-based immunofluorescence procedure that identified PC by their morphology and monoclonal light chain staining. The presence of abnormal PBPC (defined as an increase in number or proliferative rate of circulating monoclonal plasma cells) was correlated with patient status at 6 and 12 months after testing. 16 of the 57 patients progressed within 12 months and 63% of these had abnormal PBPC. In contrast, only 10% (4/41) of those patients who remained stable had abnormal PBPC. The median time to progression for patients with abnormal PBPC was 0.75 years, compared to 2.5 years for those patients without abnormal PBPC (P < 0.01). The detection of PBPC is important and helps to identify patients with active MM when other parameters suggest SMM. The lack of abnormal PBPC suggests SMM, and these patients may have a stable course without the need for immediate chemotherapy.

Adult↗

PubMed1994

IgD monoclonal gammopathy with long-term follow-up.

The presence of a serum IgD monoclonal protein (M-protein) is usually indicative of a malignant plasma cell disorder. However, one case of well-documented benign monoclonal gammopathy (BMG) of IgD type has been reported. We describe another patient with IgD monoclonal gammopathy of undetermined significance (MGUS) with long-term follow-up. In this patient an IgD lambda M-protein was found on routine serum electrophoresis. She is alive and has no evidence of multiple myeloma or amyloidosis after 8 years of follow-up. Although IgD MGUS is exceedingly rare, this case demonstrates that the presence of a serum IgD M-protein is not necessarily synonymous with a malignant plasma cell process.

Female↗

PubMed1994

Expression of shared idiotypes by paraproteins from patients with monoclonal gammopathy of undetermined significance.

We have previously demonstrated the expression of shared idiotypes by the paraproteins from approximately one-quarter of patients with multiple myeloma (MM). We have now investigated whether similar cross-reactivity is expressed in the paraproteins of patients with monoclonal gammopathy of undetermined significance (MGUS), using a panel of 32 monoclonal antibodies (MAB) generated against follicular B cell lymphomas. The paraproteins from 76/409 (19%) patients with MGUS reacted with at least one of 23 different anti-idiotypic antibodies used in this study. 18 MABs demonstrated reactivity with more than one patient's paraprotein. Moreover, 10 MABs reacted frequently (with 5-22 paraproteins). Over half (41/76) of the reactive patients' paraproteins reacted with more than one MAB from this panel. This frequency of anti-idiotypic reactivity was similar to that of previously studied patients with myeloma, chronic lymphocytic leukaemia (CLL), and follicular B-cell lymphomas. There was no correlation between specific anti-idiotypic reactivity and the propensity to develop serious disease (MM, macroglobulinaemia, amyloidosis, or other lymphoproliferative disorders) in patients with MGUS. These results suggest that MGUS is derived from cells producing antibodies that are similar to those of other B-cell malignancies and that the pattern of idiotype expression is irrelevant to malignant potential.

Antibodies, Monoclonal↗

PubMed1994

Monoclonal proteins and renal disease.

Renal insufficiency, which is present initially in almost half of patients with multiple myeloma, usually results from myeloma kidney or hypercalcemia. Neither the class of light chain nor the isoelectric point plays an important role in kidney failure. Acute renal failure must be treated with appropriate fluids and with electrolytes and hemodialysis if necessary. Plasma exchange may be helpful, but has not been proven as such. The presence of a nephrotic syndrome and a monoclonal kappa or lambda light chain in the urine almost always indicates primary amyloidosis (AL) or light-chain deposition disease. Amyloid fibrils must be distinguished from the fibrils of immunotactoid glomerulopathy.

Amyloidosis↗

PubMed1994

Immunoglobulin D multiple myeloma: presenting features, response to therapy, and survival in a series of 53 cases.

PURPOSE: To analyze the clinical and laboratory characteristics, response to therapy, and survival in 53 patients with immunoglobulin D (IgD) multiple myeloma (MM) from a single institution. PATIENTS AND METHODS: Records of all Mayo Clinic patients with IgD MM seen between January 1, 1965 and December 31, 1992 were reviewed. Survival curves were plotted according to the Kaplan-Meier method and statistically compared using the log-rank test. RESULTS: The main presenting features were bone pain (72%), fatigue (36%), weight loss (32%), extramedullary plasmacytomas (19%), and associated amyloidosis (19%). Renal function impairment and hypercalcemia were present in 33% and 22% of patients, respectively. The serum electrophoretic pattern showed an M-spike in only 60% of the patients, the remaining having either hypogammaglobulinemia or a normal-appearing pattern. Bence Jones proteinuria was identified in 96%. The type of light chain was lambda in 60% of the patients, kappa in 38%, and indeterminate in 2%. Among 45 patients assessable for response, the objective response rate was 58%. The median duration of survival in the whole series was 21 months. There was a trend for longer survival in patients given combination chemotherapy (median, 20 v 64 months; P = .09). The proportions of patients alive at 3 and 5 years were 36% and 21%, respectively. CONCLUSION: Patients with IgD myeloma usually present with a small or no visible monoclonal spike on serum electrophoresis and light-chain proteinuria, thus resembling Bence Jones myeloma. Response to therapy is similar to that observed in other myeloma types. Although the median duration of survival is shorter than that currently achieved in patients with myeloma, one third and one fifth survive for more than 3 and 5 years, respectively.

Adult↗

PubMed1994

Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945.

PURPOSE: Incidence rates of multiple myeloma appear to have increased in recent decades, but it is difficult to compare the incidence rates over time because of changes in laboratory procedures, differences in diagnostic criteria, and variations in indexing of medical records. However, Olmsted County, Minnesota, provides a rare opportunity to minimize these limitations, because the medical care has been provided mainly by the Mayo Clinic. PATIENTS AND METHODS: Records of Olmsted County residents with a diagnosis of multiple myeloma from January 1, 1978 through December 31, 1990 were reviewed. Criteria for diagnosis and residency were the same as in previous Olmsted County studies. RESULTS: The incidence rate per 100,000 age-adjusted to the 1950 United States white population was 5.4 for males and 2.8 for females; the overall rate was 4.1. The rates were age-adjusted to the 1950 United States population for comparison with earlier data from this population. The rates increased with age for both sexes. There was no significant change in incidence rates from 1945 through 1990. A comparison of the median age for Olmsted County patients with the age of those referred to the Mayo Clinic from elsewhere indicated that the local patients were appreciably older (74 v. 62 years, respectively). Thirty-two of 55 patients (58%) with multiple myeloma from 1978 through 1990 had a monoclonal plasma-cell proliferative process before the diagnosis of multiple myeloma. CONCLUSION: The incidence rate of multiple myeloma in Olmsted County, Minnesota, has not changed significantly during the past 46 years. We believe that reports of increasing rates over time are mainly due to improved case ascertainment.

Adolescent↗

PubMed1994

Myeloma and related disorders.

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

The monoclonal gammopathies.

Each monoclonal protein (M-protein, or myeloma protein) consists of two heavy polypeptide chains of the same class and subclass and two light polypeptide chains of the same type. Electrophoresis on cellulose acetate membranes is satisfactory for screening, although agarose electrophoresis is more sensitive for detecting small M-proteins. Immunoelectrophoresis should be performed when myeloma, macroglobulinemia, amyloidosis, or a related disorder is suspected. Immunofixation is useful when results of immunoelectrophoresis are equivocal. The recognition of a Bence Jones protein depends on the demonstration of a monoclonal light chain by immunoelectrophoresis or immunofixation of an adequately concentrated urine specimen. The differential diagnosis of an M-protein includes monoclonal gammopathy of undetermined significance (benign monoclonal gammopathy), multiple myeloma, solitary plasmacytoma of bone or extramedullary plasmacytoma, macroglobulinemia, lymphoma, chronic lymphocytic leukemia, and primary systemic amyloidosis.

Amyloidosis↗

PubMed1993

Newer approaches to the management of multiple myeloma.

Patients with multiple myeloma must be distinguished from those with monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Therapy should be reserved for patients with active or symptomatic multiple myeloma. The pertinent literature on the diagnosis of multiple myeloma, prognostic factors, chemotherapy, and allogeneic bone marrow transplantation, as well as autologous peripheral blood or bone marrow stem cells for rescue, was reviewed. The two most powerful prognostic factors for multiple myeloma are the bone marrow plasma cell labeling index and the beta 2-microglobulin level. Chemotherapy is the preferred initial treatment for overt, symptomatic multiple myeloma. Combinations of alkylating agents produce a higher response rate, but the survival is the same as treatment with melphalan and prednisone. The combination of alpha 2-interferon with multiple alkylating agents produces a good response. alpha 2-Interferon prolongs the duration of the plateau state after a response to chemotherapy, but it apparently does not prolong survival. Allogeneic bone marrow transplantation is possible for only 5-10% of patients with multiple myeloma. Its advantage is that the graft contains no tumor cells that can subsequently produce a relapse. However, there is a significant early mortality, the risk of graft versus host disease is troublesome, and relapse of multiple myeloma is common. Autologous bone marrow transplantation is applicable for more patients because the age limit is higher and a matched donor is unnecessary. However, two major problems exist: (1) eradication of multiple myeloma from the patient may not occur even with large doses of chemotherapy and irradiation, and (2) infused autologous bone marrow or peripheral blood stem cells contaminated by myeloma cells or their precursors may be responsible for relapse.

Antineoplastic Agents↗

PubMed1993

Coexistence of aneuploid subclones within a myeloma cell line that exhibits clonal immunoglobulin gene rearrangement: clinical implications.

A new human myeloma cell line, ANBL-6, was established and characterized at the genotypic and phenotypic levels. The cells exhibit a clonally rearranged immunoglobulin gene locus and resemble plasma cells morphologically. The ANBL-6 cells also exhibited an absolute dependence on exogenous interleukin 6 for growth. Of interest, DNA ploidy analysis suggested the existence of a near-diploid as well as a near-tetraploid population in this cell line. Cytogenetic studies confirmed the existence of two aneuploid karyotypes and further revealed a clonal relationship between the two karyotypes, as evidenced by numerous shared structural abnormalities. To determine whether the near-diploid cells functioned as stem cells for the near-tetraploid population, the near-diploid population was separated via flow cytometry and recultured prior to ploidy analysis. This population was observed to remain predominantly near-diploid over time, suggesting that these cells did not function as stem cells for the near-tetraploid population. However, the near-tetraploid cells did exhibit a growth advantage in vitro. Moreover, sequential ploidy analysis performed retrospectively on fresh bone marrow cells from the patient also suggested that there was an expansion of the near-tetraploid population during clinical relapse. These results suggest that both populations are self-regenerating and reflect the consequences of clonal evolution in the myeloma tumor. The coexistence of clonally related subclones with shared chromosomal abnormalities, however, suggests that the near-tetraploid subclone was derived from the near-diploid subclone at an unknown time during tumorigenesis.

Aneuploidy↗

PubMed1993

Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma.

BACKGROUND: The analysis of peripheral blood mononuclear cells for plasma cells and B-cell surface light chain ratios may provide additional insight on the pathogenesis of multiple myeloma and predict disease activity. The goals of this study were to correlate these parameters with clinically determined disease activity and establish a cutoff value of circulating plasma cells that could be used in future clinical trials. METHODS: Peripheral blood samples from 84 patients with monoclonal gammopathies were analyzed by an immunofluorescence, slide-based, labeling index (LI) technique for detection of plasma cells, the LI, and light chain ratios. These parameters were compared with disease activity. RESULTS: Of the 84 patients studied, 27% had inactive and 73% had active disease. The mean number of plasma cells for patients with inactive disease was 0.61 x 10(6)/l, compared with 139.6 x 10(6)/l for patients with active disease (P < 0.001). The mean ratios of involved to uninvolved light chain percentages for patients with inactive and active disease were 1.6 and 9.2, respectively (P = 0.002). The absolute number of plasma cells better predicted disease activity than the light chain ratio. By use of a cutoff value of 3 x 10(6)/l, 67% of patients with active disease were determined to have 3 x 10(6)/l or more plasma cells, and 96% of those with inactive disease had less than 3 x 10(6)/l plasma cells. CONCLUSIONS: These results suggest that detection of circulating plasma cells is a marker of disease activity in patients with plasma cell disorders and that an appropriate cutoff value is 3 x 10(6)/l or more circulating plasma cells.

Blood Cell Count↗

PubMed1993

Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma.

The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.

Adult↗