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P R Greipp

Publications and source records attributed to P R Greipp.

At least 109 records · Page 6Linked to original sources
PubMed1994

Plasma interleukin-6 and C-reactive protein levels in reactive versus clonal thrombocytosis.

PURPOSE: Evaluate the discriminatory value of plasma interleukin-6 or C-reactive protein levels in clonal thrombocytosis compared with those in reactive thrombocytosis. PATIENTS AND METHODS: A comparative analysis of quantitatively measured laboratory values in a prospectively studied group of consecutive patients. The setting was a tertiary referral center consisting of two hospitals and an outpatient clinic. Plasma interleukin-6 and C-reactive protein levels were measured in 91 consecutive patients with thrombocytosis (platelet count > or = 600 x 10(9)/L). The cause of thrombocytosis was determined by reviewing the medical histories and follow-up data without knowledge of the corresponding laboratory values. Sixty-four patients had reactive thrombocytosis, 20 had clonal thrombocytosis, and 7 had clonal thrombocytosis plus reactive thrombocytosis. Plasma interleukin-6 was measured by an enzyme-linked immunosorbent assay, and C-reactive protein was measured with rate immunonephelometry. RESULTS: Interleukin-6 levels were undetectable in all the patients with clonal thrombocytosis, whereas they were increased in 60% of the patients with reactive thrombocytosis or clonal thrombocytosis plus reactive thrombocytosis. There was a correlation between interleukin-6 and C-reactive protein levels (r = .6), and the median and range values of both levels differed significantly between the clonal thrombocytosis group and the other two groups (P < 0.0001). In 81% of the patients with reactive thrombocytosis, levels of either interleukin-6 or C-reactive protein were elevated. There was no correlation between interleukin-6 and C-reactive protein levels and the platelet count. CONCLUSIONS: An elevated interleukin-6 level is rare in uncomplicated clonal thrombocytosis and suggests reactive thrombocytosis. However, an isolated normal value has little discriminatory value. Measurement of C-reactive protein level may be used as a less expensive surrogate for measurement of interleukin-6. Repeatedly low levels of both interleukin-6 and C-reactive protein are most consistent with clonal thrombocytosis.

Aged↗
PubMed1994

Prognosis in myeloma.

OBJECTIVE: To review biologic factors that may be useful in determining prognosis in patients with myeloma. DESIGN: The currently available clinical variables and staging systems were assessed for their predictive value in myeloma, and newly proposed prognostic factors were summarized. RESULTS: Because some patients with myeloma may potentially benefit by new, more intensive therapies such as stem cell transplantation or may have prolonged survival with standard therapy, determining factors that would distinguish such patients is important. Independent prognostic factors such as the plasma cell labeling index and beta 2-microglobulin have repeatedly outperformed other prognostic clinical variables and can be combined into a system that identifies poor, intermediate, and good prognostic groups of patients with myeloma. New factors are needed to improve on the predictive value of these two variables. Studies of the biologic features of myelomas have led to the discovery of soluble interleukin 6 receptor (sIL 6R) in the serum. sIL 6R enhances the myeloma cell response to interleukin 6, a central growth factor that affects myeloma cell proliferation. Preliminary studies by the Eastern Cooperative Oncology Group show that sIL 6R predicts survival independent of the plasma cell labeling index and beta 2-microglobulin. Other proposed independent prognostic factors include cytokines and their soluble receptors, regulatory T cells, circulating myeloma cells, myeloma cell precursors, and markers of proliferation, apoptosis, and drug resistance. CONCLUSION: Because of wide variation in duration of survival, the prognosis of patients with myeloma, a fatal bone marrow plasma cell neoplasm, cannot yet be adequately predicted. Better prognostic factors are needed for stratification in clinical trials, counseling of patients, and designing of new therapeutic trials.

Humans↗
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

Bone marrow aspirate immunofluorescent and bone marrow biopsy immunoperoxidase staining of plasma cells in histologically occult plasma cell proliferative marrow disorders.

Immunofluorescent staining (immunofluorescence bone marrow aspirate) and immunoperoxidase staining (immunoperoxidase bone marrow biopsy) were compared in 26 patients with plasma cell dyscrasia and less than 10% marrow plasma cells. Their clinical diagnoses included monoclonal gammopathy of undetermined significance (13 patients), treated multiple myeloma (four patients), multiple myeloma with less than 10% marrow plasma cells (two patients), primary systemic amyloidosis (two patients), monoclonal gammopathy of undetermined significance with neuropathy (two patients), angiofollicular lymph node hyperplasia (two patients, all with the POEMS [polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes] syndrome), and primary (amyloidosis) amyloid neuropathy (one patient). The percentage of plasma cells was greater than 5% in 23% of patients and less than or equal to 5% in 77% of patients. With immunofluorescence bone marrow aspirate and immunoperoxidase bone marrow biopsy, light-chain restriction was demonstrated in 84% of all cases and accurately determined in 96% of all cases as shown by serum and urine paraprotein analysis or tissue amyloid typing. Monoclonal populations of plasma cells can be readily identified with immunofluorescence bone marrow aspirate and immunoperoxidase bone marrow biopsy in most patients with paraproteins and marrow plasmacytoses not diagnostic of multiple myeloma.

Adult↗
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↗
PubMed1992

Circulating peripheral blood plasma cells in multiple myeloma.

These studies indicate that monoclonal plasma cells can be detected in the peripheral blood of patients with active myeloma even when they are not detectable by routine WBC differentials performed on Wright-stained blood smears. These cells are usually not present in patients with MGUS and true SMM. They are detected in approximately 60% of patients with new, active MM and over 90% of patients with relapsed or refractory MM. If treatment is effective, they tend to decrease or disappear from the blood. When immunological, molecular, or cytogenetic studies are performed on peripheral blood cells from patients with MM, it must be realized that monoclonal plasma cells may be present and that they can influence the results of these tests. Although monoclonal plasma cells can circulate in the peripheral blood, it is not yet clear whether this cell represents the myeloma stem cell. It is possible that there are precursor cells that do not have plasma cell morphology in the blood or marrow that then differentiate into plasma cells. This question can only be answered by first depleting the plasma cells and then examining the remaining B-cells with appropriate immunological and molecular techniques.

Blood Cell Count↗
PubMed1992

Control of systemic capillary leak syndrome with aminophylline and terbutaline.

PURPOSE: Patients with systemic capillary leak syndrome have a characteristic triad of hypotension, hemoconcentration, and monoclonal gammopathy. They have frequent and severe attacks of hemoconcentration and hypotension accompanied by marked plasma shifts. The exact role of this monoclonal protein is unknown, but it probably leads, in some way, to an increase in capillary permeability. Despite efforts to resuscitate the patients during an acute attack, the syndrome is often fatal. Some success has been obtained in preventing the attacks with the beta-adrenergic-stimulating agent terbutaline. The purpose of this study was to determine the effectiveness of aminophylline and terbutaline in the treatment of systemic capillary leak syndrome. METHODS: Over a decade, three patients with systemic capillary leak syndrome presented at our institution. All three patients were treated with terbutaline and aminophylline. Prednisone was used during the course of treatment in each of the three patients. RESULTS: In contrast to previous reports of partial or temporary control of episodes, all three patients are alive with almost complete resolution of their recurrent attacks and have been able to return to their normal lifestyles. CONCLUSION: The regimen of terbutaline and aminophylline effectively prevents the attacks of hypotension and hemoconcentration that occur in systemic capillary leak syndrome. The role of prednisone is not clear. Until more is known about the pathophysiology of the disorder, treatment must remain empiric and supportive.

Aged↗
PubMed1992

Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor.

Soluble forms of the interleukin (IL)-2, IL-4 and IL-7 receptors which lack the transmembrane domain have been described. IL-6 is a growth factor important in the final differentiation of B-cells into plasma cells and in the pathogenesis of multiple myeloma. To determine whether the receptor for IL-6 may exist as a soluble molecule, RNA was analysed from the transformed B-cell lines U266, CESS and Daudi, from bone marrow from two myeloma patients, and from normal leukocytes. Using polymerase chain reaction, oligonucleotide primers which flank the transmembrane domain were selected to generate a 339 bp fragment. All samples produced equivalent amounts of the expected 339 bp fragment plus a smaller 245 bp fragment except Daudi which exhibited virtual absence of both. Sequence analysis of the smaller fragments from each of the five samples demonstrated the deletion of the entire transmembrane region from codons 356 (G-TG) to 387 (AG-G). The boundaries of this deletion were identical in all cases. Partial sequence analysis of the ligand-binding domain for U266 demonstrated identical sequences for the membrane-bound and soluble forms of the IL-6 receptor cDNAs. In summary, an mRNA which encodes a soluble form of the IL-6 receptor is expressed in both normal and myeloma cells.

B-Lymphocytes↗
PubMed1992

Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide.

The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3+,CD8+) or natural killer (NK) cells (CD3-,CD15+). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked DNA analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The DNA of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.

Aged↗
PubMed1991

T cell depletion using anti-CD2 coated magnetic beads simplifies the detection of peripheral blood plasma cells.

The detection of peripheral blood plasma cells is clinically important, but difficult to perform by use of routine smears. To simplify the detection process, the peripheral blood T cells from ten patients with known active multiple myeloma were depleted using anti-CD2 coated magnetic beads. In all cases, there was enrichment of the immunoglobulin (Ig) positive cells after T cell depletion (mean enrichment factor, 3.4; median, 3.2; range, 1.2-5.1) with a mean pre-bead %Ig+ cells of 7.3 compared to 20.4 for the post-bead sample (p = 0.005). The monoclonal plasma cells were similarly enriched and more easily enumerated on the microscope slides prepared from the T cell depleted sample.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Response rates and survival in primary systemic amyloidosis.

Patients (153) with biopsy-proven primary systemic amyloidosis (AL) were evaluated for their response rate to alkylating agent-based chemotherapy. Twenty-seven of the patients (18%) responded. The serum creatinine concentration had an adverse effect on response rate (P = .05). In patients with nephrotic syndrome, a normal serum creatinine value, and no echocardiographic evidence of cardiac amyloidosis, the response rate was 39% (12 of 31). Five of 34 patients with amyloid cardiomyopathy responded. Two of these five are alive 10 years after diagnosis. None of the 18 patients with amyloid peripheral neuropathy showed regression of their disease. The median time to achieve response was 11.7 months. The median survival of the 27 patients was 89.4 months and 21 of 27 survived 5 years (78%). Eight patients remain alive with a minimum follow-up of 90 months. Seven died of acute leukemia or dysmyelopoietic syndrome, a presumed complication of melphalan therapy. In the group of 126 patients who showed no response to alkylating agent-based therapy, the median survival was 14.7 months and 9 (7%) survived over 5 years. All 126 patients have died. Alkylating agent-based chemotherapy for AL is beneficial in a subset of patients and a trial of chemotherapy is strongly recommended. Those patients who do respond demonstrate survival benefit.

Amyloidosis↗
PubMed1991

Models of S-phase determination in lymphomas from flow cytometric DNA content histograms: comparison with the bromodeoxyuridine labeling index.

The estimated S-phase fraction (%S) of non-Hodgkin's lymphomas has been demonstrated to be of prognostic value. The %S can be determined by labeling index (LI) techniques or by various mathematical models applied to DNA content histograms. We performed DNA content analysis and a slide-based bromodeoxyuridine immunofluorescence LI on split samples from 117 biopsy specimens suspicious for lymphoma. The LI was compared with the %S determined by two computer models (rectangular and polynomial) with and without debris subtraction, and a manual gates computer model. In the 93 DNA diploid cases, the rectangular models had the highest correlation with the LI (R = 0.88). In the 24 aneuploid cases, the manual gates model was the most useful because of a high correlation with the LI (R = 0.70) and its ability to be used in most cases (23/24). The polynomial models had limited usefulness because they generally gave a higher %S than the LI and could be fitted in less than half of the DNA aneuploid histograms. These results suggest that in situations where the LI is not possible, an accurate %S estimate can usually be obtained with either a rectangular or manual gates model.

Bromodeoxyuridine↗
PubMed1991

Classification of amyloidosis by the detection of clonal excess of plasma cells in the bone marrow.

In 28 cases of amyloidosis, bone marrow was examined to determine whether detection of clonal excess of plasma cells could be used to distinguish immunoglobulin-derived amyloidosis from other forms of amyloidosis. Patients were selected from a group of 315 cases of biopsy-proved amyloidosis in which bone marrow aspiration and biopsy had been done. There was no detectable monoclonal immunoglobulin in the serum or in the urine in 28 patients. Of 13 patients with immunoglobulin-derived amyloidosis, a clonal excess of plasma cells in the bone marrow could be detected in 11 (sensitivity, 85%), even though no immunoglobulin could be found circulating in the serum or urine after immunofixation with two light chain antisera of different sources. The 15 remaining patients had other forms of amyloidosis; 14 had polyclonal populations of plasma cells in the bone marrow (specificity, 93%). The positive predictive value of clonal excess was 92% and its negative predictive value was 88%. We conclude that, in the subset of patients with amyloidosis who do not have a circulating M component in the serum or urine detection of a clonal excess of plasma cells is useful in characterizing the type of amyloidosis. Correct classification is important for appropriate assessment of prognosis and therapy for the group of patients.

Adult↗
PubMed1990

Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia.

Most of human follicular lymphomas possess the t(14;18) chromosome translocation that juxtaposes the IgH gene to the 3' region of bcl-2 in a head-to-tail configuration. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately of 10%) of B cell CLL. In all cases analyzed, breakpoints on chromosome 18 clustered at the 5' flanking region of the bcl-2 gene, and no rearrangements were found at the major or minor breakpoint clustering region (3' region of bcl-2 gene) typical of the t(14;18) chromosome translocation. All of the rearranged bcl-2 genes were juxtaposed with the Ig lambda or K genes in a head-to-head configuration. These results imply that the bcl-2 gene is preferentially linked to the IgL genes in CLL and could function in leukemogenesis.

Base Sequence↗
PubMed1990

Effect of sonication on paraffin-embedded tissue preparation for DNA flow cytometry.

Since the publication of paraffin block extraction procedures, flow cytometric analysis of DNA ploidy and S-phase of tumor specimens has been widely applied. DNA aneuploidy, DNA tetraploid (elevated G2/M), and elevated S-phase are clinically significant in some tumor systems. True DNA tetraploid cell lines will contain a large 4c population and perhaps an 8c population; samples with cell aggregates will also contain a 6c population. Microscopic examination of samples having a 6c peak revealed nuclei with adhering debris and doublets, triplets, and larger nuclear aggregates. After sonication, a uniform suspension of single nuclei without adherent debris was seen. In addition to reducing the percent of G2/M cells, sonication also reduced S-phase percent such that it was closer to the bromodeoxyuridine labeling index. The DNA ploidy classification of specimens was also compared pre- and post-sonication. Four of 96 breast cancer samples changed classification; all were specimens in which the histogram became cleaner and a small DNA aneuploid peak became apparent after sonication.

Breast Neoplasms↗