BACKGROUND: To determine the efficacy of epoetin alfa for the treatment of the anemia of multiple myeloma, a prospective, randomized, placebo-controlled, double-blind clinical trial enrolled 25 patients with the anemia of multiple myeloma and a hematocrit less than 0.30. METHODS: Epoetin alfa, 150 U/kg, or a matching volume of placebo was administered subcutaneously three times per week for 6 weeks. If the criterion for a response was not met, the dose was doubled. After 12 weeks, nonresponders in the placebo arm were switched to an open-label study of epoetin alfa at a dose of 150 U/kg for 6 weeks. After 6 weeks, the dose was doubled if no response was obtained. A partial response was defined as an increase of 6 percentage points or greater in the hematocrit without transfusion. A complete response required a final hematocrit of 0.38 or greater without transfusion. Complete responders had reduction of epoetin alfa to the lowest dose capable of maintaining the complete response. RESULTS: Twenty patients were evaluable for response to therapy. During the double-blind phase, six patients who were receiving epoetin alfa had a complete response, one had a partial response, and three were non-responders. No responses occurred in the placebo arm. In the open-label phase, of the 10 patients who were originally receiving placebo, three had a complete response, one had a partial response, and six were nonresponders. Chemotherapy, pretreatment serum erythropoietin levels, disease duration, and reticulocyte count did not predict the response to epoetin alfa. The median final dose for the responding group was 120 U/kg three times per week to maintain a hematocrit greater than 0.38. There was no effect on the course of the myeloma, and no hypertension was seen. CONCLUSION: Treatment with epoetin alfa is effective and safe in patients with the anemia of multiple myeloma.

Anemia↗

PubMed1995

Amyloidosis.

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Aged↗

PubMed1995

Hamilton Smith--Nobel Prize winner in medicine or physiology.

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History, 20th Century↗

PubMed1995

Monoclonal gammopathy of undetermined significance (MGUS).

MGUS is characterized by a serum M-protein concentration of less than 30 milligrams (3 g/dl), fewer than 10% plasma cells in the bone marrow, no or only small amounts of M-protein (Bence Jones protein) in the urine, the absence of lytic lesions, anaemia, hypercalcaemia and renal insufficiency, and most importantly, stability of the M-protein and failure of the development of additional abnormalities. Electrophoresis on agarose, followed by immunoelectrophoresis or immunofixation for the identification of the type of M-protein, is recommended. In 1994, 971 patients at the Mayo Clinic were found with a serum M-protein. The most frequent diagnosis was MGUS, which occurred in 52% of patients. MGUS is found in approximately 3% of people older than 70 years and in at least 1% of those aged over 50. The incidence of monoclonal gammopathies increases with advancing age and is higher in African-Americans than in Caucasians. Two hundred and forty-one patients from the Mayo Clinic with a monoclonal gammopathy but no evidence of MM, macroglobulinaemia, amyloidosis, lymphoma or related disorders were followed for 24-38 years. In 62 patients (26%), multiple myeloma, macroglobulinaemia, amyloidosis or a malignant lymphoproliferative disorder developed (the actuarial rate of development of serious disease at 10 years was 16%; at 20 years, 33%; and at 25 years, 40%). Thirty patients (12%) were alive and had a stable M-protein value. In 23 patients (10%), the serum M-protein level increased to 30 milligrams (3 g/dl) or more, but they did not require therapy for myeloma or related disorders. Fifty-two per cent of patients (126) died of unrelated diseases without the development of a malignant plasma cell lymphoproliferative disorder. The actual rate of development of serious disease was the same for those with IgG, IgA and IgM M-proteins. Differentiation of MGUS from myeloma or macroglobulinaemia is difficult. The M-protein value must be measured periodically and clinical evaluation carried out to determine whether or not serious disease has developed.

Diagnosis, Differential↗

PubMed1995

Phase III study comparing vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) chemotherapy with VAD plus recombinant interferon alfa-2 in refractory or relapsed multiple myeloma. An Eastern Cooperative Oncology Group study.

PURPOSE: This clinical trial was designed to compare the effectiveness of vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) with VAD plus interferon alfa-2 in patients with refractory or relapsed multiple myeloma. PATIENTS AND METHODS: Between January 1990 and May 1992, 47 eligible patients with multiple myeloma who had failed one prior chemotherapeutic regimen were accrued to a multiinstitutional prospective randomized clinical trial. The trial was halted early because of poor accrual. RESULTS: After a minimum follow-up of 13 months, the objective overall response rate was 28% (25% in the VAD group, 30% in the VAD plus interferon group). The response duration and overall survival were similar for the two treatment groups, with medians of 3.6 and 8.3 months, respectively. Life-threatening or lethal nonhematologic toxicity was seen in 27%. Interferon did not appear to increase the frequency of toxic responses. CONCLUSION: This study shows no advantage to the use of interferon combined with VAD in refractory or relapsing myeloma. However, the small sample size decreased the statistical power to recognize small differences if present. Moreover, the survival data do not suggest a clear advantage to the administration of vincristine or doxorubicin as a 96-hour infusion compared with results of studies using bolus administration combined with high-dose corticosteroids.

Adult↗

PubMed1995

Clinicopathological correlates of CD56 expression in multiple myeloma: a unique entity?

Prior studies have suggested that loss of plasma cell CD56 expression in multiple myeloma defines a unique patient subset and that CD56 expression reliably discriminates between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). We conducted a study of 68 untreated patients with MM from a single institution to define the clinicopathological correlates of CD56 expression. We find CD56 expression in 55% of MM. Lack of CD56 expression does not define a unique clinicopathological or prognostic entity in MM. Strong CD56 expression can also be found in MGUS and does not help to distinguish from MM.

Antigens, CD↗

PubMed1995

Detection of monoclonal plasma cells in the peripheral blood stem cell harvests of patients with multiple myeloma.

We evaluated the harvest product from 47 patients undergoing peripheral blood (BP) stem cell collections for monoclonal plasma cells (PC) using a sensitive immunofluorescence technique. 60% (28/47) had documented tumour cells in the apheresis product. The 32 patients in plateau had a mean of 1.62 x 10(6) PC/l v 74.64 x 10(6) in 15 relapsed patients (P < 0.01). 32% (6/19) of patients without any tumour cells in the initial sample had them detected on a subsequent apheresis sample. In four cases (all treated with GM-CSF) small numbers of tumour cells were detected initially but became undetectable on a subsequent sample.

Blood Component Removal↗

PubMed1995

Serial studies of peripheral blood myeloma cells in patients with multiple myeloma: when is the optimal time for stem cell harvest?

This study serially quantitated monoclonal plasma cells (PC) in the peripheral blood (PB) of 33 patients with multiple myeloma (MM) at diagnosis, after therapy, and at relapse using a sensitive immunofluorescence technique. The goal was to learn which disease phase is best for harvesting PB stem cells free of monoclonal PC. In 24 chemotherapy responders, 88% (21/24) had circulating PC at diagnosis; after therapy, 63% (15/24) had none, 33% (8/24) had < 3 x 10(6)/L, and only one had > or = 3 x 10(6)/L. In nine cases who failed to respond to initial chemotherapy, 89% (8/9) had high levels (> or = 3 x 10(6)/L) of circulating PC at diagnosis that remained high after therapy. In the relapse phase, 88% (21/24) had circulating PC and 63% (15/24) had high numbers. This study demonstrates that the PB is least likely to have circulating monoclonal PC during the period after successful chemotherapy. Patients who fail to respond to initial chemotherapy or are in relapse are likely to have tumor cells in the PB.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995