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Biomedical subjects

J P Garton

Publications and source records attributed to J P Garton.

11 recordsLinked to original sources
PubMed1995

Epoetin alfa for the treatment of the anemia of multiple myeloma. A prospective, randomized, placebo-controlled, double-blind trial.

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

Refractory and relapsing multiple myeloma treated by blood stem cell transplantation.

Between June 1989 and June 1992, 12 patients with advanced multiple myeloma underwent peripheral blood stem cell autotransplantation after high-dose chemotherapy and radiotherapy. The conditioning regimen included melphalan (140 mg/m2), high-dose cyclophosphamide (120 mg/kg), methylprednisolone (2 g daily x 7), and total body irradiation (9-12 Gy). Transplant morbidity included severe mucositis (n = 7) and acute renal failure (n = 2) related to infusion of the stem cells. Engraftment was delayed (n = 4) in this heavily pretreated population, and two patients had complete graft failure. Despite the advanced nature and chemotherapy-refractory state of their disease, 11 of 11 evaluable patients achieved an objective response. Six patients survived to leave the hospital, and four remain alive--one died of acute leukemia induced by prior melphalan exposure. Three of the four are relapse-free at a median of 24.9 months (range, 18-28 months). Some patients with advanced refractory multiple myeloma can achieve objective responses from highdose chemoradiotherapy with peripheral blood stem cell rescue. Harvesting peripheral blood stem cells from high-risk patients early in their disease for later use may decrease the risk of graft failure. Peripheral blood stem cell transplantation after high-dose chemotherapy and total body irradiation can produce durable responses in patients with advanced refractory myeloma.

Acute Kidney Injury↗
PubMed1995

A phase II study of high-dose methylprednisolone in refractory or relapsed multiple myeloma.

A single-arm, phase II perspective clinical trial was done in a tertiary care setting to determine the efficacy of high-dose methylprednisolone in the treatment of patients with refractory or relapsed multiple myeloma. Twenty patients who had failed at least one chemotherapeutic regimen received methylprednisolone (2 g) intravenously three times weekly for 8 weeks. After 8 weeks, responders were placed on a maintenance phase of 2 g intravenously weekly with an 8-week reinduction at the time of relapse. Five patients died within the first month of therapy. There were two complete responses, two objective responses and three minor responses. The median survival for all 20 patients was 2.2 months. Median survival for the seven responders was 19 months, with a relapse-free survival of 15 months. Five patients survived at least 16 months. High-dose methylprednisolone is an easily administered, relatively nontoxic, and effective therapy in a subset of patients with multiple myeloma.

Adult↗
PubMed1991

Rheumatic manifestations in myelodysplastic syndromes.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis with possible transformation to acute nonlymphocytic leukemia. We describe a patient with refractory anemia with excess blasts with unusual rheumatic manifestations of vasculitis, migratory synovitis, arthralgias, and myalgias. A retrospective review over a 6-month period of 162 patients with myelodysplastic syndromes found 16 patients (10%) with several rheumatic manifestations. We divided these manifestations into 4 different categories: cutaneous vasculitis, "lupus-like syndrome," neuropathy, and patients with both a rheumatic disease and a myelodysplastic syndrome. There were 7 with cutaneous vasculitis including leukocytoclastic vasculitis and other individual cases of urticarial vasculitis and panniculitis; 3 with lupus-like manifestations with histological evidence of an inflammatory process; 3 with neuropathic manifestations including peripheral neuropathy, mononeuritis with foot drop, and chronic inflammatory demyelinating polyneuropathy; and 3 patients in which their myelodysplastic syndrome was diagnosed after their rheumatic disease was known, including rheumatoid arthritis. Sjögren's syndrome and mixed connective tissue disease. The class with refractory anemia with excess blasts had 9 patients with rheumatic manifestations but also had the largest number of patients in the study (46/162 or 29%). Three of the 16 patients died, all from the refractory anemia with excess blasts class, reflecting the known mortality in this group of patients. We believe there is a significant association between myelodysplastic syndromes and rheumatic manifestations.

Adult↗
PubMed1987

The spectrum of IgM monoclonal gammopathy in 430 cases.

IgM monoclonal gammopathy consists of a broad spectrum of diseases, ranging from apparently benign to malignant conditions. In a long-term follow-up study of 430 patients in whom a monoclonal IgM serum protein had been identified, 242 (56%) had monoclonal gammopathy of undetermined significance, 71 (17%) had Waldenström's macroglobulinemia, 28 (7%) had lymphoma, 21 (5%) had chronic lymphocytic leukemia, 6 (1%) had primary amyloidosis, and 62 (14%) had other malignant lymphoproliferative diseases. More than two-thirds of the patients died, and the most common cause of death was a lymphoid malignant process. Almost a fifth of the patients with an apparently benign monoclonal gammopathy subsequently had a lymphoid malignant lesion (in one patient, more than 20 years after the detection of the serum M protein). The median duration of time from the recognition of the M protein until the development of a malignant lymphoid disease ranged from 4 to 9 years. An increased number of lymphocytes or plasma cells on bone marrow examination was not a reliable indicator of the likelihood of such an outcome. Thus, follow-up of these patients should be conducted indefinitely.

Adult↗
PubMed1986

Primary amyloidosis (AL) in families.

We report the occurrence of immunoglobulin-related amyloidosis (AL) in three separate families, each family having two members affected. None of the six patients had evidence to suggest the presence of familial amyloidosis (AF). Previously, immunoglobulin-related amyloidosis (AL) was considered to be a sporadic disease process. Because of the occasional familial occurrence of other monoclonal gammopathies such as monoclonal gammopathy of undetermined significance, multiple myeloma, and macroglobulinemia of Waldenström, amyloidosis (AL) should be added to the list of immunopathies with a familial predisposition.

Adult↗
PubMed1986

A monoclonal antibody reactive with a subset of human plasma cells.

A mouse monoclonal antibody (R1-3) raised against a human plasmacytoma xenograft and reactive with human plasma cells is described. The antibody reacts with a subset of plasma cells and lymphocytes, but is nonreactive with granulocytes, normoblasts, thymus, spleen or T lymphocytes. Flow cytometer double labelling experiments showed that approximately 50% of R1-3 positive bone marrow cells expressed surface immunoglobulin, but no R1-3 positive cells also expressed B1 or Leu 4. In a myeloma patient the R1-3 reactive cells were found to have a higher rate of DNA proliferation and were aneuploid as determined by flow cytometry. The R1-3 antigen is expressed on late B lymphocytes and early plasma cells.

Animals↗
PubMed1985

Primary systemic amyloidosis. Comparison of melphalan/prednisone versus colchicine.

This is the first prospectively randomized study of the use of melphalan/prednisone and colchicine in the treatment of primary systemic amyloidosis. One hundred one patients were stratified according to their dominant clinical manifestation. Forty-nine patients initially received melphalan/prednisone and eight subsequently had colchicine added to their regimen. Fifty-two patients initially received colchicine and 35 subsequently required melphalan/prednisone because of progressive disease. There was no difference in survival when the two groups were analyzed in aggregate (melphalan/prednisone, 25.2 months versus colchicine, 18 months; p = 0.23). When the survival of patients receiving only one regimen was analyzed or when survival was analyzed from the time of entry into the study to the time of death or progression of disease, significant differences (p less than 0.001 and p less than 0.0001, respectively) were evident, favoring melphalan/prednisone. This study suggests that melphalan/prednisone is superior to colchicine in the treatment of primary amyloidosis, but to confirm this impression, a study without a crossover group is necessary.

Amyloidosis↗
PubMed1984

Multiple myeloma: circulating lymphocytes that express plasma cell antigens.

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1-3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

Antigens, Surface↗