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Biomedical subjects

R A Kyle

Publications and source records attributed to R A Kyle.

At least 163 records · Page 9Linked to original sources
PubMed1997

Hepatic amyloidosis: clinical appraisal in 77 patients.

The purpose of this study was to assess prognostic factors and survival in patients with liver involvement in immunoglobulin light-chain amyloidosis. Comparisons were made with other patients with immunoglobulin light-chain amyloidosis who did not have liver involvement. A total of 77 consecutively seen patients were evaluated: 19 had hepatic amyloidosis and 58 had amyloidosis without liver involvement. Eighteen of 19 patients with liver amyloidosis could be histologically diagnosed without needle biopsy of the liver. All but 2 had a detectable free light chain in the serum or urine, distinguishing this from other infiltrative liver processes. Patients with liver amyloid had significantly higher alkaline phosphatase levels and C-reactive protein levels compared with patients without hepatic amyloid. The majority of patients had extrahepatic involvement predominantly in the kidney (47%) or heart (42%). The presence of hyposplenism was not a good screening test for the presence of hepatic amyloid. Seven of 19 patients responded to chemotherapy with objective regressions of the clinical manifestations of renal, hepatic, or cardiac involvement. We conclude that the survival of patients with liver involvement in amyloidosis is no different than other patients with amyloidosis. This results from the high proportion of patients having associated renal or cardiac involvement. Most patients can be diagnosed without a liver biopsy when a monoclonal protein is found in the serum or urine. Serum albumin and C-reactive protein levels appear to distinguish patients with liver involvement from those without.

Adult↗
PubMed1997

Monoclonal gammopathy of undetermined significance and solitary plasmacytoma. Implications for progression to overt multiple myeloma.

MGUS is characterized by the presence of a serum M-protein less than 3 g/dL; fewer than 10% plasma cells in the bone marrow; no, or only small amounts of, M-protein in the urine; absence of lytic lesions, anemia, hypercalcemia, and renal insufficiency; and, most importantly, stability of the M-protein and failure of development of other abnormalities, MGUS is found in approximately 3% of persons older than 70 years and in 1% of those 50 years or older. During long-term follow-up, approximately one fourth of patients develop multiple myeloma (MM), amyloidosis, macroglobulinemia, or a similar malignant lymphoproliferative disorder. Actuarial rate of development of serious disease was 16% at 10 years, 33% at 20 years, and 40% at 25 years in our experience. The interval from recognition of the M-protein to the diagnosis of MM ranged from 2 to 29 years (median, 10 years). The size of the M-protein, hemoglobin value, percentage of bone marrow plasma cells, amount of light-chain excretion, presence of hypercalcemia or renal insufficiency, and presence of lytic bone lesions are often helpful in differentiating MGUS from MM and macroglobulinemia. The plasma cell labeling index and the presence of circulating plasma cells in the peripheral blood are indicators of active disease; however, there are no findings at the diagnosis of MGUS that reliably distinguish patients who will remain stable from those in whom a malignant condition will develop. Thus, a physician must perform serial measurements of the M-protein in the serum and periodic evaluation of the pertinent clinical and laboratory features to determine whether MM, macroglobulinemia, systemic amyloidosis, or related disorders have developed. Solitary plasmacytoma is characterized by the presence of a tumor consisting of monoclonal plasma cells identical to those in MM. In addition, skeletal roentgenograms must show no lytic lesions, a bone marrow aspirate must contain no evidence of MM, and immunoelectrophoresis or immunofixation of the serum and concentrated urine should show no M-protein. Exceptions to the presence of an M-protein occur, but therapy of the solitary lesion often results in disappearance of the M-protein. Tumoricidal irradiation (4000 to 5000 cGy) for approximately 4 weeks is the treatment of choice. Overt MM occurs in approximately 50% of patients with solitary plasmacytoma. Progression occurs in most patients within 3 years. The three patterns of failure are (1) development of MM, (2) local recurrence, and (3) development of new bone lesions in the absence of MM.

Adult↗
PubMed1997

Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation.

We sought to determine whether circulating tumor cells in the blood stem cell harvest from patients with multiple myeloma are associated with a shortened disease-free survival. Prospective analysis was performed in 33 patients of blood obtained at leukapheresis for future transplantation. An immunofluorescence microscopy procedure identified the tumor cells by their morphology and monotypic light chain staining. Eighteen patients had increased (> or = 0.2 x 10(6)/l) monoclonal plasma cells circulating in the blood at stem cell harvest. Fifteen of the 18 have relapsed, with a median relapse-free survival of 6.2 months. Of 15 patients with < 0.2 x 10(6) cells/l, seven have relapsed, with a median relapse-free survival of 22.5 months (P = 0.008). Patients with circulating plasma cells showed a trend toward shorter overall survival (P = 0.078). In a multivariate analysis using the bone marrow plasma cell labeling index and beta 2-microglobulin, the absolute number of plasma cells in the stem cell harvest achieved borderline significance for predicting relapse-free survival (P = 0.057). In conclusion, increased monoclonal plasma cells in the blood stem cell harvest are associated with a shortened relapse-free survival. This does not necessarily indicate that the circulating plasma cells were responsible for relapse. These results, however, have implications with regard to the timing of obtaining blood stem cells for patients who are candidates for ablative chemotherapy.

Adult↗
PubMed1997

Factors influencing platelet recovery after blood cell transplantation in multiple myeloma.

We sought to determine factors that impact on the recovery of platelets after blood cell transplantation in patients with multiple myeloma. We performed retrospective analyses in 51 patients undergoing blood cell transplantation for multiple myeloma. The proportional-hazards model was applied to determine significant risk factors. Of 51 transplants, 14 patients failed to achieve a platelet count of 50 x 10(9)/l. Median time to a neutrophil count of 0.5 x 10(9)/l was 10.5 days. Median time to achieve a platelet count of 50 x 10(9)/l was 32 days. Multivariate analysis revealed that cyclophosphamide and G-CSF priming before collection of hematopoietic precursors (P < 0.001) was a positive predictor of rapid engraftment and prior exposure to melphalan given orally (P = 0.02) was a negative predictor of subsequent platelet engraftment. The number of mononuclear cells collected, the patient's disease status at the time of transplant and the presence of circulating plasma cells in the harvested product did not have a significant impact on time to platelet engraftment. We conclude that cyclophosphamide and G-CSF priming shortened the time to achieve platelet engraftment compared with G-CSF alone. Prior exposure to melphalan delayed platelet engraftment and can lead to complete failure of platelet recovery. Stem cells should be collected before melphalan administration in patients with multiple myeloma who are candidates for possible blood cell transplantation.

Adult↗
PubMed1997

The amino acid sequence of the glycosylated amyloid immunoglobulin light chain protein AL MS.

The authors report on the amino acid sequence of the glycosylated amyloid protein AL MS. The amyloid fibrils were extracted from the spleen of a patient (MS.) with amyloidosis. The protein AL MS was purified from the amyloid fibrils by gel filtration. SDS-PAGE performed on the purified protein material showed glycosylated protein bands in the range of 22 to 32 kDa, corresponding to polymerization of N-terminal fragments. The protein was characterized by amino acid analysis and Edman degradation. Tryptic digest combined with Staphylococcal V8 protease, chymotrypsin and pyroglutamate aminopeptidase digestion, as well as cleavage with BNPS-skatole, established the complete amino acid sequence of 168 residues. The protein was compared to other proteins in the SWISSPROT databank, showing homology with the immunoglobulin light chain variable subgroup lamda I. AL MS showed some unique amino acid substitutions. Highly conserved residues Gly(57) and Arg(61), were exchanged to arginine and glutamine, respectively, possibly altering the three- dimensional structure of the protein.

Amino Acid Sequence↗
PubMed1996

Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial.

Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ras mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta 2-microglobulin levels, labelling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P < .02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P < .02). To determine if the status of ras mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ras mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-alpha showed statistically significant survival differences between mutant and wildtype ras status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wild-type ras had a median survival of 4.0 years (P < .01).

Adult↗