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P R Greipp

Publications and source records attributed to P R Greipp.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prognostic value of bone marrow angiogenesis in multiple myeloma.

We studied the prognostic value of angiogenesis grading and microvessel density estimation in newly diagnosed multiple myeloma. Seventy-five patients with newly diagnosed myeloma, treated on Eastern Cooperative Oncology Protocol E9486 and Intergroup study 0141 (S9321) at the Mayo Clinic, were studied. Bone marrow microvessels were examined using immunohistochemical staining for von Willebrand factor. Determination of microvessel density and angiogenesis grading was done in a blinded manner. There was a strong correlation between microvessel density and the plasma cell labeling index, rho 0.42, P < 0.001. Angiogenesis grade was also significantly associated with the plasma cell labeling index. Fifteen % of patients with low-grade angiogenesis had a high labeling index (>1%). In contrast, 47% of patients with intermediate or high-grade angiogenesis had high labeling indices (P = 0.02). Overall survival was significantly different among those with high-, intermediate-, and low-grade angiogenesis, with median times of 2, 4, and 4.4 years, respectively (P = 0.02). Similarly, patients with microvessel density >50/x400 field had poorer survival compared with those with 50 or fewer microvessels/field, median survival 2.6 versus 5.1 years, respectively (P = 0.004). There was a strong association between angiogenesis grade and microvessel density (P < 0.001). We conclude that bone marrow angiogenesis is a predictor of poor survival in newly diagnosed myeloma. Angiogenesis is correlated with the plasma cell labeling index but not the bone marrow plasma cell percentage. A simple visual grading of angiogenesis is an efficient alternative to microvessel density estimation.

Bone Marrow↗
PubMed1999

The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma: phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486.

BACKGROUND: Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Group (ECOG) study suggested that the rates of complete response (CR) and survival were increased with a regimen that alternated IFN with chemotherapy. The current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiCy) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS: From February 1988 to May 1992, the ECOG entered previously untreated patients with active multiple myeloma on a study in which they were randomized to VBMCP (vincristine 1.2 mg/m(2) administered intravenously [i.v.] on Day 1, BCNU 20 mg/m(2) i.v. on Day 1, melphalan 8 mg/m(2) administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m(2) i.v. on Day 1, and prednisone 40 mg/m(2) p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(alpha2), the latter given at 5 Mu/m(2) 3 times a week starting on Day 22 of each 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 years were also randomized to a third treatment that substituted cyclophosphamide 600 mg/m(2) i.v. on Days 1-4 and prednisone 100 mg/m(2) p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS: Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients of 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of the three regimens revealed no significant difference in the rates of survival or objective response (OR). However, CRs were increased among patients treated with VBMCP + rIFN(alpha2) compared with VBMCP alone (18% vs. 10%, P = 0.03). Patients treated with VBMCP + rIFN(alpha2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.035). There was a greater response rate with the IFN regimen among elderly patients (OR and CR = 67% and 31%, respectively) and patients with immunoglobulin A (IgA) myeloma (OR and CR = 83% and 29%, respectively). Severe infections were seen as often with VBMCP as with VBMCP + rIFN(alpha2) (13% vs. 15%), but they were more frequent with VBMCP + HiCy (25%). CONCLUSIONS: VBMCP + rIFN(alpha2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(alpha2) induction therapy to produce CR and more durable responses, as well as its activity in older patients and in those with IgA myeloma, suggest that this therapy has important biologic activity in myeloma and merits further clinical investigation.

Adult↗
PubMed1999

Treatment of the systemic capillary leak syndrome with terbutaline and theophylline. A case series.

BACKGROUND: The systemic capillary leak syndrome is a rare idiopathic disorder characterized by recurrent episodes of hypotension and hemoconcentration due to sudden transient extravasation of 10% to 70% of plasma. Mortality rates 5 years after diagnosis have been reported to be 76%. OBJECTIVE: To assess the efficacy of a prophylactic regimen for the systemic capillary leak syndrome. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Eight patients followed over the past 18 years. INTERVENTION: Oral terbutaline plus aminophylline or theophylline. MEASUREMENTS: Long-term clinical follow-up. RESULTS: During a median follow-up of 9 years (range, 2 to 18 years), two patients (25%) died: one during an acute episode and one of complications related to long-term corticosteroid therapy. The other six patients are alive and healthy. The frequency and severity of the episodes decreased by a median of 30-fold. Recurrences were associated with decreased serum theophylline levels, possibly caused by enzyme induction or autoinduction. The extended-release form of medication was more successful. Sympathomimetic side effects were significant. CONCLUSIONS: A regimen of terbutaline and theophylline seems to be effective prophylaxis against the systemic capillary leak syndrome. Maintenance of therapeutic drug levels was associated with favorable results.

Adrenergic beta-Agonists↗
PubMed1999

Long-term survival (10 years or more) in 30 patients with primary amyloidosis.

The median survival in primary systemic (AL) amyloidosis is less than 18 months. No published series of patients with AL amyloidosis have reported survival of more than 10 years. The records of all Mayo Clinic patients with a diagnosis of AL amyloidosis between January 1, 1966 and March 1, 1987 were reviewed. Patients with secondary amyloidosis, familial amyloidosis, senile systemic amyloidosis, and localized amyloidosis were excluded. During the 21 years of the study, 841 patients with AL amyloidosis were seen. Of these, 29 were excluded because the diagnosis was made at autopsy, and 2 others were excluded because no follow-up data were available. Actuarial survival for the 810 patients was 51% at 1 year, 16% at 5 years, and 4.7% at 10 years. Thirty patients survived for 10 years or more after the histologic diagnosis of AL amyloidosis; all received alkylating-agent therapy. In 14 patients, the monoclonal protein disappeared from the serum or urine. Of 10 patients with nephrotic syndrome, 4 had an objective response. Congestive heart failure, older age, creatinine value of 2 mg/dL or more, bone marrow plasma cell value of 20% or more, platelet count of 500 x 10(9)/L or less, and the presence of peripheral neuropathy were underrepresented in the 10-year survivors and are unfavorable prognostic features. Five percent of patients with AL amyloidosis survived for 10 years or more.

Adult↗
PubMed1999

Phase II trial of high-dose dexamethasone for previously treated immunoglobulin light-chain amyloidosis.

Immunoglobulin light-chain amyloidosis (AL) is a rare disorder characterized by production of a monoclonal light chain. This insoluble light chain, or a fragment thereof, deposits in tissues as amyloid and results in disruption of organ function and, ultimately, in death. Although melphalan and prednisone are beneficial in approximately 30% of patients with the disease, many patients fail to respond, and the median survival with this disease remains < 2 years. There is a need for new agents for those patients who fail to respond to melphalan-based chemotherapy. A study was undertaken of high-dose dexamethasone in the treatment of 19 patients with AL because of reports of its benefits in previously untreated patients with amyloidosis and its known activity in the management of multiple myeloma, which has many characteristics in common with AL. In this cohort, 3 of 19 patients showed an objective organ response of the disease. The median survival of the entire group was 11.2 months. We conclude that high-dose dexamethasone therapy is of occasional benefit in patients previously treated for amyloidosis. Combining dexamethasone with other therapies may increase the response rate.

Aged↗
PubMed1999

Prognostic significance of the S-phase fraction of light-chain-restricted cytoplasmic immunoglobulin (cIg) positive plasma cells in patients with newly diagnosed multiple myeloma enrolled on Eastern Cooperative Oncology Group treatment trial E9486.

The bone marrow plasma cell labeling index (PCLI) as measured by bromodeoxyuridine uptake is a well-established independent prognostic factor for patients with newly diagnosed multiple myeloma, but the test is not easily done in most laboratories. The purpose of this study was to determine if the proliferative activity (% S-phase) as determined by two-color flow cytometry for cytoplasmic immunoglobulin (cIg) light chain and DNA content also had prognostic significance. As part of Eastern Cooperative Oncology Group clinical trial E9486, 500 patients had successful performance of the bone marrow PCLI. Of 349 patients who had flow cIg and DNA content cytometry, 210 had adequate data to reliably calculate S-phase %. Patients with low % S-phase fraction (<2%) had a significant overall survival advantage over patients high % S-phase fraction (>/=2%), median survivals 4.1 vs. 2.9 years (P = 0.032). Measurement of the S-phase % by flow cytometry gives significant prognostic information in patients with newly diagnosed myeloma. However, in multivariate analysis, S-phase % did not add prognostic information when PCLI was in the model. S-phase % added prognostic information only when all cases with flow measurement of S-phase % were included, and when PCLI was excluded from the model. Discriminating a population of only cIg positive cells proved difficult in patients with a low percentage of bone marrow plasma cells. Methodology to measure S-phase % in patients with a low percent plasma cells is needed before this technique can be used for diagnosis and prognosis in myeloma.

Aged↗
PubMed1999

Phase II trial of high-dose dexamethasone for untreated patients with primary systemic amyloidosis.

Primary systemic amyloidosis is the disorder that results from the deposition of insoluble immunoglobulin light chain fragments. Patients seen within 30 days of diagnosis have a median survival of 13 months. Patients treated with melphalan and prednisone have a median survival of 17 months. There is a need for new therapies. A prospective study was undertaken of high-dose dexamethasone in the treatment of 25 patients with previously untreated primary systemic amyloidosis. Treatment was similar to that given to patients with multiple myeloma. In this cohort, three patients showed objective regression with organ-specific improvement of the disease. The median survival of the entire group was 13.8 months. High-dose dexamethasone is of occasional benefit in patients with amyloidosis but does not appear to be superior to melphalan and prednisone chemotherapy.

Adult↗
PubMed1999

Cytogenetic abnormalities correlate with the plasma cell labeling index and extent of bone marrow involvement in myeloma.

Chromosomal abnormalities have biologic and prognostic significance in multiple myeloma, especially among patients with relapsed disease. We report the relationship between chromosomal abnormalities and known prognostic factors such as plasma cell labeling index (PCLI) and bone marrow plasma cell involvement in 75 consecutive patients undergoing autologous stem cell transplantation for relapsed or refractory myeloma. Thirty of 70 patients (43%) had a chromosomally abnormal clone in their bone marrow, and in most cases the karyotype was complex (> 3 abnormalities). Patients with an abnormal clone on cytogenetic analysis had a higher PCLI (median, 1.4) than patients with a normal karyotype (0.2) (P < 0.001). Bone marrow plasma cell percentage also differed: median 48% versus 20%, respectively (P < 0.001). The PCLI and bone marrow plasma cell percentage correlated positively with the percentage of abnormal metaphases on conventional cytogenetic analysis: rho 0.60 (P < 0.001) and 0.46 (P < 0.001), respectively. We categorized patients into those with 20% or more abnormal metaphases, less than 20% abnormal metaphases, and only normal metaphases. The median PCLI values were 3.3, 1.1, and 0.3, respectively (P < 0.001). The bone marrow plasma cell percentage median values were 62%, 40%, and 25%, respectively (P = 0.003). Chromosomal abnormalities may offer a proliferative advantage to the neoplastic plasma cell, thereby leading to an unfavorable outcome.

Adult↗
PubMed1999

Prognostic factors in multiple myeloma.

There is significant variation in the survival of patients with myeloma. This article reviews the major prognostic factors in myeloma and the evidence supporting their usefulness in clinical practice and research. The factors reviewed include serum beta 2-microglobulin, bone marrow plasma cell labeling index, cytogenetics, plasmablastic morphology, and other standard clinical laboratory variables. Novel factors such as bone marrow angiogenesis are also discussed. A combination of independent factors provides greater prognostic information than any one factor alone, and survival data using various combinations of prognostic factors are presented.

Aging↗
PubMed1999

Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma.

Transplantation after high-dose chemotherapy prolongs survival in patients with multiple myeloma compared with standard therapy. It is unclear whether the optimal timing of transplantation is immediately after induction chemotherapy or whether stem cells may be cryopreserved for transplantation at subsequent progression or relapse. In this study, stem cells were collected within 6 months of diagnosis, followed by transplantation only at progression of myeloma. One hundred and eighteen patients with multiple myeloma had stem cells collected and cryopreserved. Eleven had transplants early in the disease after they demonstrated failure to respond to primary therapy. The remaining 107 were eligible for transplants when there was evidence of progressive disease. Of the 118 patients, 67 had transplants, nine died of progressive disease before transplantation, and 42 remain alive in plateau phase. The median survival of the group is 58.5 months; 67 are alive. Serum beta2-microglobulin, bone marrow labeling index (S phase), and hemoglobin level predicted overall survival (P < 0.006, P < 0.001, and P < 0.01, respectively). We conclude that early cryopreservation of blood stem cells followed by transplantation at progression is a feasible approach to therapy in patients with myeloma. The underlying biology of the disease has a greater impact on survival than the timing of transplantation. A prospective randomized trial is required to answer definitively the question of the optimal timing of blood cell transplantation.

Adult↗
PubMed1999

Beta2-microglobulin and bone marrow plasma cell involvement predict complete responders among patients undergoing blood cell transplantation for myeloma.

We studied the prognostic value of clinical and laboratory variables, measured before blood cell transplantation, in predicting complete response among patients undergoing autologous blood cell transplantation for relapsed or primary refractory myeloma. Sixty-seven patients who underwent transplantation for relapsed or primary refractory myeloma were studied. The overall response rate was 90%, and the complete response rate was 33%. Low beta2-microglobulin (< or =2.7 mg/l) was associated with a significantly better complete response rate compared with high levels (54 vs 19%, P = 0.002). Similarly, the complete response rate was 39% when the bone marrow plasma cell percentage was low (<40%) and 21% with greater involvement (P = 0.04). Complete response rate was 50% when beta2-microglobulin and bone marrow plasma cell percentage were low, 36% if either was high, and 12% when both were high (P = 0.01). Median survival measured from initial diagnosis of myeloma was 51 months. Overall survival after transplantation was better among responders who achieved complete response than those who did not: median survival, 24 vs 11 months, P = 0.04 (log-rank) and 0.009 (Gehan-Wilcoxon). Attainment of a complete response independently predicted better survival in a multivariate analysis. beta2-Microglobulin and bone marrow plasma cell percentage predict complete responders among patients undergoing transplantation for myeloma.

Adult↗
PubMed1999

Autologous stem cell transplantation for relapsed and primary refractory myeloma.

The aim of this study was to evaluate the effectiveness of autologous stem cell transplantation for patients with relapsed or primary chemotherapy-refractory myeloma. Seventy-five patients, 50 men and 25 women, ages 33-68 years (median, 53 years), who underwent transplantation for relapsed or primary refractory myeloma were studied. Patients underwent transplantation 5-88 months (median, 23 months) after diagnosis of myeloma. The time to transplantation was significantly shorter in patients with refractory disease than for those with relapsed myeloma (median, 8 and 32 months, respectively; P < 0.001). Patients with primary refractory myeloma had a significantly lower plasma cell labeling index than those with relapsed disease (P = 0.008). There were no differences in overall and complete response rates between patients with primary refractory and relapsed disease. The median survival of the entire cohort from diagnosis was 53 months. Overall survival from transplantation among patients with relapsed myeloma receiving therapy, relapsed myeloma off therapy, and primary refractory myeloma was significantly different (P = 0.04), with median times of 12, 21 and 30 months, respectively. Progression-free survival also was different (P < 0.001), with median times of 7, 13, and 26 months, respectively. We conclude that overall and progression-free survival in patients with primary refractory myeloma appear better than in patients with relapsed disease and need further study.

Adult↗
PubMed1999

Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma.

Although most of the initial studies in angiogenesis were done on solid tumors, there is now data suggesting the importance of angiogenesis in hematologic malignancies. We estimated bone marrow microvessel density before autologous stem cell transplantation and at the time of response in 13 patients with myeloma (seven complete and six partial responders) using an immunohistochemical stain for factor VIII-related antigen (von Willebrand factor). Baseline microvessel density was significantly different between bone marrow samples from patients with myeloma and morphologically normal, staging marrows from patients with limited stage Hodgkin's disease, mean (+/- s.d.) 294 (+/-115)/mm2 vs 93 (+/-26/mm2, respectively, P = 0.001. After transplantation, microvessel density continued to be high in myeloma samples compared to samples from control patients with limited stage Hodgkin's disease, mean (+/- s.d.) 230 (+/-68)/mm2, P = 0.003. There was no difference in microvessel density at the time of complete or partial response compared to values prior to transplantation. This report confirms that increased angiogenesis is found in myeloma bone marrow prior to transplantation, and suggests that increased angiogenesis persists even after complete response.

Adult↗
PubMed1999

Measurement of apoptosis and proliferation of bone marrow plasma cells in patients with plasma cell proliferative disorders.

The proliferative rate of malignant plasma cells, as measured by the plasma cell labelling index (PCLI), is an important prognostic factor in multiple myeloma (MM); however, the PCLI alone is probably Inadequate to describe tumour growth because it ignores the idea that myeloma cells may have a reduced rate of apoptosis. The aims of this study were to develop a flow cytometric method to measure the apoptosis index of fresh marrow plasma cells and develop a plasma cell growth index (PCGI) that related both proliferation and apoptosis to disease activity. Marrow aspirates were obtained from 91 patients with plasma cell disorders and the plasma cells in apoptosis were identified by either 7-amino actinomycin-D (7-AAD) or annexin V-FITC three-colour flow cytometry. The median plasma cell apoptotic index (PCAI) for patients with monoclonal gammopathy of undetermined significance (MGUS), smouldering or indolent myeloma (SMM/IMM), and new multiple myeloma (MM) was 5.2, 3.4 and 2.4, respectively (P=0.03, MGUS v MM). The median PCLI for these same patient groups was 0.0, 0.2 and 0.6, respectively (P<0.001, MGUS v MM). The paired PCLI and PCAI for each sample were used to derive the PCGI=2 + [PCLI-(O.1)(PCAI)]. The median PCGI for patients with inactive disease (MGUS, SMM/IMM or amyloidosis) was 1.8 compared to 2.4 for those with active disease (new or relapsed MM) (P<0.001). These results suggest that a decrease in the PCAI may be a factor in the progression from MGUS to SMM to overt MM.

Apoptosis↗
PubMed1999

Clinical significance of the translocation (11;14)(q13;q32) in multiple myeloma.

The most common chromosomal translocation in multiple myeloma (MM) is t(11;14)(q13;q32). Here, we describe the clinical characteristics of patients with MM who have this translocation. We have identified 24 patients at our institution who had t(11;14)(q13;q32) as determined by standard cytogenetic analysis (CC). Seven patients had the translocation detected at the time of original diagnosis and 17 at the time of relapse. Median survival in all patients after original diagnosis was 43 months; median survival after the translocation was detected was 11.9 months. Four patients had a clinical diagnosis of plasma cell leukemia. Most patients had an elevated beta2-microglobulin (13/20 had >4 microg/ml). The bone marrow (BM) labeling index (LI) of patients, at the time of translocation detection, was elevated in most (median 1.4%, 17/23 patients had BMLI > or = 1%). Of the 24 patients, 19 (79%) died of disease progression and 5 (21%) were alive with disease at last follow-up. Lytic lesions, bone pain, or compression fractures eventually developed in all patients. Patients with MM who have t(11;14)(q13;q32) detected by standard cytogenetics seem to have an aggressive clinical course.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Prospective randomized trial of melphalan and prednisone versus vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis.

PURPOSE: Primary systemic amyloidosis is an immunoglobulin deposition disorder in which insoluble light chains cause organ dysfunction and death. The established conventional therapy is treatment with melphalan and prednisone. We investigated whether treatment with multiple alkylating agents improved the response rate or survival time, compared with melphalan and prednisone therapy. PATIENTS AND METHODS: We treated 101 patients with biopsy-proven primary amyloidosis. The patients were randomly assigned to receive melphalan and prednisone (52 patients) or vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (49 patients). Patients were stratified according to the presence of cardiac involvement, time from diagnosis to randomization, serum beta2-microglobulin level, and whether peripheral neuropathy was the major manifestation of the disease. RESULTS: The median duration of survival after randomization was 29 months, with no differences in survival time between the two groups. There were 29 patients who fulfilled the response criteria: 15 in the vincristine, carmustine, melphalan, cyclophosphamide, and prednisone arm and 14 in the melphalan and prednisone arm. CONCLUSION: Therapy with multiple alkylating agents did not result in a higher response rate or longer survival time, compared with standard melphalan and prednisone treatment in patients with primary systemic amyloidosis.

Adult↗