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P R Greipp

Publications and source records attributed to P R Greipp.

At least 127 records · Page 7Linked to original sources
PubMed1990

Beta 2-microglobulin predicts survival in primary systemic amyloidosis.

PURPOSE: The study assessed whether beta 2-microglobulin levels predict survival or response in patients with primary systemic amyloidosis without associated multiple myeloma. PATIENTS AND METHODS: The study group consisted of 131 untreated patients with biopsy-proven primary systemic amyloidosis diagnosed and evaluated at the Mayo Clinic. No patient had multiple myeloma. The minimum follow-up of surviving patients is 8 years. No patient was lost to follow-up. RESULTS: The median survival of patients with an increased beta 2-microglobulin level was 10.8 months, compared with patients with a normal beta 2-microglobulin level (less than or equal to 2.7 micrograms/mL, 0.23 mumol/L) of 32.9 months (p less than 0.001). In a multivariate proportional-hazards model, the best model included congestive heart failure (p less than 0.0001) and increased beta 2-microglobulin levels (p less than 0.05). After adjustment for the presence of congestive heart failure, beta 2-microglobulin level remained significant. When the analysis was restricted to those patients with normal renal function, the median survival of those with an elevated beta 2-microglobulin level was 9.1 months versus 39.4 months for those with a normal level (p less than 0.001). The serum level of beta 2-microglobulin was increased in patients with nephrotic-range proteinuria with or without renal insufficiency (p = 0.05). CONCLUSION: The serum beta 2-microglobulin level should be measured routinely in all patients with primary systemic amyloidosis because it provides a useful objective factor to identify subsets of patients with this disease who have unfavorable outcomes.

Adult↗
PubMed1989

The plasma cell labeling index: a valuable tool in primary systemic amyloidosis.

The plasma cell labeling index (LI) is of value in predicting prognosis in multiple myeloma. Primary systemic amyloidosis (AL) is a plasma cell dyscrasia that shares many features with myeloma. We obtained bromodeoxyuridine LI on 125 patients who presented with AL, 22 of whom also had overt multiple myeloma. Forty-six patients had a plasma cell LI greater than 0%. Of the 46 patients with an elevated LI, 19 (41%) had multiple myeloma as compared with three (4%) of the 79 patients with an LI = 0 (P less than .0001). A response to chemotherapy was seen in 14 (30%) of 46 patients with an LI greater than 0, as compared with ten (13%) of 79 patients with an LI of 0 (P = .015). The median survival of the high LI group was 14.6 months v 29.8 months for the low LI group (P = .02). In the low LI group, 29% are projected to be alive at 60 months, as compared with 20% in the high LI group. When patients with myeloma were excluded from the analysis, the LI did not predict response but continued to indicate a survival disadvantage (P less than .05). The major utility of the LI was in identifying those patients most likely to have multiple myeloma and those AL patients with a poor prognosis (median survival, 14.1 months).

Amyloidosis↗
PubMed1989

Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma.

We analyzed 49 patients with multiple myeloma (MM) using propidium iodide (PI) staining and flow cytometry to assess DNA content of MM cells in bone marrow. In 12 patients the presence or absence of DNA content aneuploidy could not be determined by analysis of single-parameter DNA histograms alone. Using forward light scatter measurement, resolution of ploidy was readily obtained in all but three cases. Assuming the DNA content of the low light scatter population to be diploid, we were able to classify 7 cases as hypodiploid and 39 as hyperdiploid or diploid. Hyperdiploid or diploid patients survived a median of 24 months and hypodiploid patients only 2.5 months. We conclude that multiparameter analysis of DNA content and light scatter provides easier analysis for the presence or absence of aneuploidy. Patients with DNA content hypodiploidy have a short survival.

Bone Marrow↗
PubMed1989

Phase II trial of amsacrine in patients with multiple myeloma.

Seventy-four previously treated patients with multiple myeloma were treated with Amsacrine (m-AMSA) 120 mg/m2 every 3 weeks. A good response was observed in two patients (3%), and improvement was seen in three patients (4%). Severe toxicity was observed in 33% of patients who received three or more courses of treatment. This dose and schedule of m-AMSA in multiple myeloma is usually ineffective.

Adult↗
PubMed1989

Monoclonal gammopathies: new approaches to clinical problems in diagnosis and prognosis.

When a patient presents with monoclonal gammopathy, a wide variety of clinical conditions must be considered. The importance of distinguishing accurately between patients with stable monoclonal gammopathies and those with overt multiple myeloma cannot be over-emphasised. The bone marrow examination with plasma cell labeling index, and newer techniques such as magnetic resonance imaging and computed tomography can improve diagnostic discrimination. In difficult cases, the detection of small numbers of circulating myeloma cells, the peripheral blood B-cell labeling index, and light chain isotype suppression may bring better diagnostic resolution. These tests may also be used to help assess disease activity. If the diagnosis is multiple myeloma, prediction of outcome assumes clinical importance. There are widely disparate survivals among patients with different clinical presentations. Standard clinical assays or a combination of these as in clinical staging do not provide sufficient prediction of outcome but are routinely available and therefore widely used. Independent predictive tests such as the plasma cell labeling index and beta 2-microglobulin improve prognostic accuracy. Ploidy analysis and immunophenotyping are additional variables that may assume more importance as the results of ongoing studies appear. Other promising approaches include detection of oncogene and multiple drug resistance gene expression. All such techniques will become more relevant as we apply more intensive treatment earlier in the disease course, particularly for the younger myeloma patients in whom the prognosis is poor.

Adult↗
PubMed1989

Rapid S-phase determination of non-Hodgkin's lymphomas with the use of an immunofluorescence bromodeoxyuridine labeling index procedure.

Cell kinetic measurements are currently being investigated to determine if they are useful in the clinical management of patients with non-Hodgkin's lymphomas (NHLs). Although the tritiated thymidine labeling index (TLI) is the standard method of S-phase measurement, it is difficult to perform. The authors describe a slide-based immunofluorescence labeling index (LI) method that uses 5-bromo-2-deoxyuridine (BrdUrd) as the pulsing medium and a monoclonal antibody (BU-1) to BrdUrd. The BrdUrd LI was performed on 217 NHLs and compared with routine histologic results. The authors found a median BrdUrd LI of 0.9% for low-grade NHLs; 7.5% for intermediate-grade; 10.4% for high-grade; and 2.2% for T-cell NHLs. This method provides a rapid, reliable S-phase measurement that can be easily performed in the clinical laboratory. It should replace the TLI and allow wider application of S-phase measurements in the NHL.

Antibodies, Monoclonal↗
PubMed1988

Peripheral blood B cell labeling indices are a measure of disease activity in patients with monoclonal gammopathies.

Labeling indices (LI) provide a rapid measure of the bone marrow (BM) plasma cell proliferation rate and are useful in the diagnosis and prognosis of monoclonal gammopathies. Because circulating B cells may be a part of the neoplastic clone, we examined peripheral blood B cells that were producing the same cytoplasmic light chain isotype as the patient's monoclonal; protein (M-protein) and determined the peripheral blood LI (PBLI) by a two-color immunofluorescence bromodeoxyuridine method. The 105 patients studied were divided into three disease activity groups by standard clinical criteria. Median PBLI was 0.2% for the 29 patients with inactive monoclonal gammopathies (monoclonal gammopathy of undetermined significance [MGUS] and smoldering multiple myeloma [SMM]), 0.8% for the 35 patients with new, untreated multiple myeloma (MM), and 1.7% for the 41 patients with relapsed MM. These differences between groups were statistically significant (P less than .001, Wilcoxon). Four patients had high PBLI but clinically inactive gammopathy at the time of study, and all developed active MM within 6 months that required treatment. In 92 patients a BMLI was performed simultaneously with the PBLI (rank correlation coefficient, 0.69). In patients with new, untreated MM, use of both tests identified 72% of patients (23 of 32) with high LI, rather than 56% (18 of 32) by BMLI alone or 63% (20 of 32) by PBLI alone. These results suggest that PB B cells bearing the same cytoplasmic light chain isotype as the monoclonal protein are part of the malignant clone and can be kinetically active. The LI of these cells can provide a measure of disease activity and may help to differentiate active from inactive disease.

B-Lymphocytes↗
PubMed1988

Value of beta 2-microglobulin level and plasma cell labeling indices as prognostic factors in patients with newly diagnosed myeloma.

Beta 2-microglobulin (beta 2M) has been proposed as a prognostic factor in multiple myeloma (MM), but beta 2M levels are reported to correlate with other prognostic indicators such as stage and creatinine level. This study addressed the independent prognostic values of these and other variables, including plasma cell labeling indices (LI), in patients with newly diagnosed MM. beta 2M levels were measured with an enzyme-linked immunosorbent assay. LI were determined with a [3H]thymidine autoradiography method. By multivariate analysis and Kaplan-Meier survival analysis, the uncorrected beta 2M level remained the most significant prognostic factor after adjustment for age. Stage and creatinine level were closely related to beta 2M level and were no longer predictive of outcome after adjustment for age and beta 2M. Plasma cell LI varied independently of beta 2M level and remained predictive. A subset of patients with plasma-blastic myeloma had poor survival since beta 2M level and plasma cell LI were high. By using beta 2M level and LI, three risk groups were defined: low (beta 2M less than 4 micrograms/mL and LI less than 0.4%, median survival 48 months); intermediate (beta 2M less than 4 micrograms/mL and LI greater than or equal to 0.4%, median survival 29 months); and high (beta 2M greater than or equal to 4 micrograms/mL, median survival 12 months). Such grouping may better identify MM patients who might benefit from new treatment regimens.

Bone Marrow↗
PubMed1987

Immunofluorescence labeling indices in myeloma and related monoclonal gammopathies.

We measured plasma cell labeling indices (LI) in 52 patients with monoclonal gammopathies. Cytoplasmic reactivity with polyspecific or kappa- and lambda-specific light chain anti-Ig reagents identified monoclonal plasma cells, plasmablasts, and lymphocytoid plasma cells. Among newly diagnosed untreated patients, a high immunofluorescence LI distinguished those with multiple myeloma (MM) from those with stable monoclonal gammopathies (P less than 0.002). Among treated patients with MM, those in the plateau phase of the disease had low LI, whereas patients in the relapse phase or early in treatment had high LI. The immunofluorescence LI correctly classified three more patients with newly diagnosed MM than did the tritiated thymidine LI technique. LI specific for the neoplastic plasma cells resulted in excellent discrimination of patients with active disease. Because results are easily and rapidly obtained, this technique is useful clinically.

Amyloidosis↗
PubMed1986

S-phase detection with an antibody to bromodeoxyuridine. Role of DNase pretreatment.

We have previously described a monoclonal antibody (BU-1) to 5-bromo-2-deoxyuridine (BrdUrd) that is useful for measurement of cell cycle S-phase. BU-1 hybridoma supernatant reacted with incorporated BrdUrd after the cells had been ethanol fixed; without a requirement for acid or base denaturation. We have found that this reactivity is lost if purified antibody is used, if the culture supernatants are heated, or if a mycoplasma-free hybridoma line is isolated. The supernatant contained endogenous DNase activity that was a result of mycoplasma infection of the cell line. This DNase activity was required for staining the cells with BU-1 in the absence of other denaturation steps. The endogenous DNase could be substituted for by the addition of bovine pancreatic DNase I. The disruption of the double stranded DNA structure with an enzyme rather than with harsh chemical or heat treatments does not affect protein structure or cellular morphology and allows the detection of incorporated BrdUrd of morphologic or antigenic cell subsets. DNase pre-treatment may also be useful for detection of other 'hidden' DNA antigens.

Antibodies, Monoclonal↗
PubMed1986

Amplification of RNA and DNA specific for erb B in unbalanced 1;7 chromosomal translocation associated with myelodysplastic syndrome.

Previous work has established the presence of an unbalanced chromosome abnormality [+der(1),t(1;7)(p11;p11)] in some therapy-associated myelodysplastic disorders. Recently the EGF receptor has been found to reside at 7p11. Using a probe specific for erb B oncogene, which encodes a truncated form of the EGF receptor, we examined RNA and DNA derived from bone marrow and peripheral blood mononuclear cells from three patients with myelodysplastic syndromes (MDS) and one with acute lymphocytic leukemia (ALL), all bearing an abnormal clone in their bone marrow with a similar unbalanced 1;7 translocation. DNA-excess slot blot hybridization to 5'-32p-labeled cellular RNA revealed from ten- to thirtyfold enhancement in accumulation of mRNA specific for erb B in both peripheral blood and bone marrow cells of the three MDS patients when compared to normal controls. In addition, enhancement of H-ras mRNA accumulation was detected in some, though expression of other genes such as actin, N-ras, myc, src, B-lym, and 20 other genes was not found to be enhanced. Increased erb B expression was not apparent in mononuclear cells from patients with other hematologic disorders such as chronic lymphocytic leukemia, Hodgkin's disease, or lymphoma. Southern blot analysis of restriction-enzyme-cleaved DNA from three MDS patients with an unbalanced 1;7 translocation revealed that erb B gene was amplified at least twentyfold in peripheral blood white blood cells, while levels of actin hybridization were comparable to those of the controls. No such amplification was evident in the ALL patient. Our data suggest that +der(1),t(1;7)(p11;p11) chromosomal anomalies can be specifically associated with amplification of erb B DNA and RNA sequences.

Chromosomes, Human, Pair 1↗
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↗
PubMed1986

Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases.

One hundred sixty-eight patients with primary systemic amyloidosis (AL) were identified. Median survival after diagnosis was 12 months and ranged from 4 months for patients presenting with congestive heart failure to 50 months for those presenting with peripheral neuropathy only. Utilizing the proportional-hazards model in a stepwise multivariate fashion to evaluate the simultaneous influence of putative risk factors as of diagnosis revealed that congestive heart failure, urine light chain, hepatomegaly, and multiple myeloma were the major factors adversely affecting survival during the first year after diagnosis. Serum creatinine, multiple myeloma, orthostatic hypotension, and monoclonal serum protein were the most important variables adversely affecting survival for patients surviving 1 year. These models were used to categorize patients according to the variables in the models into low-, moderate-, and high-risk groups for the first year after diagnosis and separately for subsequent years. The influence of these variables on survival is important in stratification of patients randomized to prospective clinical trials.

Adult↗