Biomedical subjects

P R Greipp

Publications and source records attributed to P R Greipp.

At least 73 records · Page 4Linked to original sources

PubMed1999

Plasmablastic morphology is an independent predictor of poor survival after autologous stem-cell transplantation for multiple myeloma.

PURPOSE: To study the prognostic value of plasmablastic morphology after autologous stem-cell transplantation for relapsed or primary refractory myeloma. PATIENTS AND METHODS: Seventy-five patients were studied. Investigators blinded to the clinical details of the individual cases reviewed bone marrow aspirate slides to determine plasmablastic classification. Plasmablasts were defined using strict, well-described criteria. Plasmablastic morphology was considered to be present (plasmablastic myeloma) when 2% or more plasmablasts were present in the plasma-cell population. RESULTS: Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Twenty-eight percent of patients had plasmablostic morphology. A significantly greater proportion of patients with plasmablastic morphology had abnormal cytogenetics compared with those with nonplasmablastic classification (73% v 31%, respectively; P = .003). The overall survival rate measured from the time of transplantation was significantly worse in patients with plasmablastic morphology compared with those without (median survival time, 5 months v 24 months, respectively; P < .001). Progression-free survival time was shortened also, with a median time of 4 months compared with 12 months, respectively (P < .001). In the multivariate analysis, plasmablastic classification was the most powerful prognostic factor after transplantation for both overall (P = .001) and progression-free survival rates (P < .001). We also identified three risk groups based on plasmablastic morphology: plasma-cell labeling index, lactate dehydrogenase, and cytogenetics. The median overall survival time was 38 months when none of these factors was abnormal, 17 months with one abnormal factor, and 8 months with two or more abnormal factors (P < .001). CONCLUSION: Plasmablastic morphology is a powerful independent predictor of poor survival rate after autologous stem-cell transplantation for relapsed or primary refractory myeloma.

Adult↗

PubMed1999

Evaluation of the proliferative index as a prognostic factor in diffuse large cell lymphoma: correlation with the International Index.

The reasons for differences in outcome between groups of patients with diffuse large cell lymphoma (DLCL) defined by clinical prognostic factors are largely unknown. Measures of cell proliferation may offer a biological explanation for these differences. This study tested the hypothesis that these survival differences between the groups defined by established prognostic factors were due to the proliferative index. The bromodeoxyuridine labeling index (LI), a measure of the S-phase fraction, was prospectively determined on fresh tumor specimens obtained at initial diagnosis in 80 patients with DLCL seen between 1986-1993 at a single institution. Patients were grouped using prognostic factors that were significant in a univariate analysis as well as the International Index (IPI). The LI in each of these groups was compared to determine whether the differences in outcome between the groups could be explained by differences in the LI. The median LI for all patients was 5.1% (range: 0.1-25%). When the predictive effect of the LI on response and survival was analyzed, the LI did not correlate with complete response or disease-free survival (DFS). There was a trend, however, for patients with a lower LI to have a poorer overall survival (p=0.06). When the patients were analyzed using the International Index (IPI), the mean LI for patients in the low-risk, low-intermediate, high-intermediate and high risk groups was 7.1%, 10.0%, 6.4% and 6.6% respectively (p=0.41). When analyzed separately, there was no significant difference in the LI for any of the patient groups defined by significant prognostic factors. The only difference in the LI was that the median LI in patients with T-cell DLCL was significantly lower than the LI in patients with B-cell DLCL (p=0.001) and these patients had an inferior complete response rate (p=0.001), disease-free survival (p=0.003) and overall survival (p=0.015). In this study, the LI, a measure of lymphoma cell proliferation, was not a significant prognostic factor for response, disease-free survival or overall survival. Furthermore, the LI did not explain the differences in outcome between patient groups defined by the IPI. However, a lower LI seen in patients with T-cell DLCL may account for their poorer response to therapy and inferior survival when compared to patients with B-cell DLCL.

Adolescent↗

PubMed1999

Is flow cytometric DNA content hypodiploidy prognostic in multiple myeloma?

Hypodiploid multiple myeloma is uncommon when assessed by DNA content flow cytometry, having been reported in less than 6% of patients with newly diagnosed multiple myeloma. Previous studies have shown these patients to be unresponsive to therapy and to have short survival. To address this further, we studied 349 of 504 patients eligible for Eastern Cooperative Oncology Group (ECOG) treatment trial E9486 and laboratory correlative study E9487 who had marrow mononuclear cells available for ploidy analysis. Marrow samples were studied by dual channel flow cytometry, using propidium iodide to measure the DNA content and kappa and lambda light chain antisera to identify the clonal cells. A DNA index < 0.95 was considered hypodiploid. Five patients (1.4%) were found to have hypodiploid DNA content in their marrow plasma cells. Three of the 5 patients with hypodiploid myeloma had a partial objective response to chemotherapy, which is not different from the overall objective response rate for all patients enrolled on E9486. All five patients with hypodiploid multiple myeloma died within 4 years from diagnosis, but these patients had a similar overall median survival (2.6 years) compared to the patients with diploid DNA content. Our studies confirm the poorer survival of patients with diploid versus hyperdiploid myeloma; we cannot confirm, however, the previously reported very poor outcome associated with hypodiploid myeloma using DNA content flow cytometry. Hypodiploid DNA content of plasma cells by flow cytometry may not be as ominous a factor as previously reported.

Aged↗

PubMed1998

Plasmablastic morphology--an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group.

We studied the prognostic significance of plasmablastic (PB) multiple myeloma (MM) in Eastern Cooperative Oncology Group Phase III trial E9486. Two reviewers independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85% concordance (P < .0001). These PB cases had significantly lower hemoglobin and serum albumin levels, higher calcium and beta 2-microglobuin levels, and higher percentage BM plasma cells (PC) by immunofluorescence. They had higher bone marrow PC labeling indices, higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan, cyclophosphamide, and prednisone (VBMCP) alone; VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2 (rIFNalpha2). Although the numbers are low, patients with PB had a significantly lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P < .0001]), but not with added rIFNalpha2. Event-free and overall survival of PB MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no survival difference between the patients who were classified as PB by both reviewers versus patients classified as PB by only one reviewer. We conclude that PB MM is a discrete entity associated with more aggressive disease and shortened survival. Tumor cell ras mutations and increased sIL-6R may contribute to a higher proliferation rate and reduced survival. There were significant improvements in response and progression with the addition of HiCy and rIFNalpha2 to VBMCP, but the numbers were small and improved survival could not be shown.

Adult↗

PubMed1998

Primary plasmacytoma at the site of exit wounds after electrical injury.

We report a case of primary plasmacytoma occurring 12 years after electrical injury. Roentgenograms showed multiple well-circumscribed lytic lesions involving both the right and left tibial diaphyseal regions. Bone biopsy from the left tibial region showed sheets of monoclonal myeloma cells. No evidence of multiple myeloma was found. The patient was treated with local radiation to both tibias and had no evidence of recurrence 6 years later. In conclusion, we report the first case of primary plasmacytoma of both tibias that occurred after electrical injury 12 years before.

Adult↗

PubMed1998

A novel three-color, clone-specific fluorescence in situ hybridization procedure for monoclonal gammopathies.

We have developed a three-color cytoplasmic immunoglobulin (cIg) and fluorescence in situ hybridization (FISH) technique to detect plasma cell chromosomal aneuploidy in patients with multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and amyloidosis (AL). Immunofluorescent-labeled antibodies to detect light chain expression and six directly labeled alpha-satellite chromosome specific enumeration probes (CEP) were used simultaneously to detect aneuploidy of the plasma cells. The six probes were specific for chromosomes 7, 9, 11, 15, 18, and X. The technique was tested in 12 consecutive patient samples (5 MM, 2 MGUS, 3 SMM, and 2 AL). Based on the alpha-satellite signals, we found trisomic clones for CEP 7 (4 of 12), CEP 11 (4 of 12), CEP X (1 of 12), CEP 9 (8 of 12), CEP 15 (7 of 12), and CEP 18 (5 of 12). Trisomic clones of at least one of the six chromosomes were present in 9 of 12 patients. We believe that this technique efficiently identifies monotypic plasma cells and permits simultaneous analysis of numeric chromosome anomalies by FISH in emerging neoplastic cells. We are in the process of applying this technique to a series of about 100 newly diagnosed monoclonal gammopathy patients.

Adult↗

PubMed1998

Detection of monoclonal plasma cells in the peripheral blood of patients with primary amyloidosis.

We evaluated the blood from 150 patients with primary AL-amyloidosis for circulating monoclonal plasma cells using a sensitive slide-based immunofluorescence technique. The percentage of monoclonal blood plasma cells (BPC) that were in S-phase was determined by the bromodeoxyuridine labelling index (BLI). Monoclonal BPC were detected in 16% (24/150) of patients. The median number of monoclonal BPC was 1 x 10(6)/l and 4.6% (7/150) of patients had a high number. The BLI was zero in all but three patients. This study demonstrates that monoclonal plasma cells circulate in the peripheral blood of patients with AL-amyloidosis.

Amyloidosis↗

PubMed1998

T-helper phenotypes in the blood of myeloma patients on ECOG phase III trials E9486/E3A93.

T-helper blood populations are frequently altered in multiple myeloma (MM). We measured the numbers of naive and activated cell subsets in the blood of a cohort of both previously untreated and treated MM patients. Two-colour flow cytometry to detect total CD4+, CD4+, CD4 5RA+ (naive) and CD4+, CD45RO+ (activated) subsets was then used to quantify the T-cell subsets in controls and MM patients. Previously treated MM patients either on or off treatment (n = 105) had significantly reduced (P< 0.0001) total CD4 and naive/activated cells than controls. Previously treated MM patients sampled for naive/activated cells while currently off therapy (n = 45) had no difference in the levels of CD4 and naive/activated cells compared to the currently treated patients (n = 60). However, newly diagnosed patients (n = 58) had a significantly reduced total CD4 (P = 0.023) and activated CD4 (P = 0.004), but not naive CD4 subsets, compared to controls. CD19+ cell levels above 125/microl were positively associated with higher T-helper cell levels. There was a strong positive association for better overall survival for patients with >395 CD4 cells/microl (P = 0.0001). These data indicate that MM patients at diagnosis have altered T-helper subsets, with a selective reduction in activated but not naive cells. Subsequent chemotherapy or the disease process contributes to a further reduction in CD4 cells. Importantly, the association of higher CD19+ cell levels with higher T helper cells indicates that certain myeloma patients can be identified with a more quantitatively intact immune system.

Adult↗

PubMed1998

Multiple myeloma and the translocation t(11;14)(q13;q32): a report on 13 cases.

Complex cytogenetic abnormalities have been described in patients with multiple myeloma (MM). To better understand the significance of the most frequent translocation observed in MM, we studied the clinical characteristics of patients with MM and the t(11;14)(q13;q32) abnormality. A search of the cytogenetic database at the Mayo Clinic identified patients with MM and t(11;14)(q13;q32). The medical records were reviewed for the clinical characteristics of these patients. We identified 13 patients with MM and t(11;14)(q13;q32) determined by standard cytogenetic analysis: in 10 patients the abnormality was detected at the time of relapse (three with previously normal results of cytogenetic examination). At the time the translocation was detected, plasma cell (PC) leukaemia was clinically diagnosed in two patients. The median number of circulating PCs, as determined by the cytoplasmic immunofluorescence of T-cell-depleted peripheral blood mononuclear cells, was 1.1x10(9)/l (mean 1.74; range 0.0017-6.26x10(9)/l). On linear regression analysis there was a strong correlation between the number of circulating PCs and the number of bone marrow PCs. The median survival after demonstration of the translocation was 8.1 months. Of all patients, 10 died of disease progression and three were alive. Patients with MM who have t(11;14)(q13;q32) seem to have an aggressive clinical course, even when the abnormality is detected at the time of diagnosis, with evidence of many circulating PCs.

Adult↗

PubMed1998

Chromosomal abnormalities in systemic amyloidosis.

Primary systemic amyloidosis (AL) is a plasma cell disorder characterized by deposition of monoclonal light chains in different organ systems. Although multiple and complex numerical chromosomal abnormalities have been described in patients with multiple myeloma, it is currently unknown whether such changes occur in systemic amyloidosis. Bone marrow samples from 21 patients with AL were studied by standard cytogenetics and interphase fluorescence in situ hybridization (FISH) for the presence of numerical chromosomal abnormalities. We tested for six chromosomes (7, 11, 9, 15, 18 and X) using centromere-specific probes. The monoclonal plasma cells were identified by simultaneous fluorescent staining of the monotypic cytoplasmic immunoglobulin. We compared these results with those obtained from 19 patients with monoclonal gammopathy of undetermined significance (MGUS) and normal controls. Multiple numerical chromosomal abnormalities were detected in AL by interphase FISH, including trisomy of chromosomes 7 (42%), 9 (52%), 11 (47%), 15 (39%), 18 (33%) and X (13% in women and 54% in men). Monosomy of chromosome 18 was seen in 72% of cases. Previous exposure to alkylator therapy did not appear to correlate with these abnormalities. No significant difference was observed in the prevalence of these abnormalities between AL and MGUS. Multiple chromosomal numerical abnormalities were detected by interphase FISH analysis in patients with AL, especially monosomy of chromosome 18. Aneuploidy in the monotypic plasma supports a neoplastic nature for the disorder.

Adult↗

PubMed1998

Paclitaxel as the initial treatment of multiple myeloma: an Eastern Cooperative Oncology Group Study (E1A93).

The authors assess the activity and toxicity of paclitaxel in previously untreated patients with multiple myeloma. Eighteen patients with previously untreated multiple myeloma were enrolled. Paclitaxel was given in a dose of 250 mg/m2 by a continuous intravenous infusion for 24 hours every 21 days for four cycles. All patients received granulocyte colony stimulating factor in a dose of 5 microg/kg each day until the absolute neutrophil count was 10,000/mm3. All patients were evaluated after four cycles. Four (29%) objective responses were observed in the 14 eligible patients. No complete responses occurred. Three lethal toxicities were observed, two were the result of neutropenic sepsis. Sixty-one percent of patients experienced some type of severe nonhematologic toxicity. Patients who received four cycles of paclitaxel were given further treatment at the discretion of the investigator. The median survival of all eligible patients was 2.8 years, which is comparable with the median survival with melphalan and prednisone of 2.3 years or vincristine, carmustine, melphalan, cylophosphamide, and prednisone of 2.4 years. Paclitaxel in the dosage used in this study has prohibitive toxicity. The four (29%) responses in 14 evaluable untreated patients indicates that paclitaxel is active in the treatment of multiple myeloma. No complete remissions were recorded. Further studies using paclitaxel in a smaller dose, in combination with other agents, or using one of the paclitaxel analogs may be useful in the treatment of multiple myeloma.

Adult↗

PubMed1998

Is multidrug resistance (P-glycoprotein) an intrinsic characteristic of plasma cells in patients with monoclonal gammopathy of undetermined significance, plasmacytoma, multiple myeloma and amyloidosis?

Multiple myeloma is not a curable disease, and most patients relapse after plateau phase. Drug resistance is a major problem in effective chemotherapy in this kind of disease. Current approaches are aimed at reversing or preventing drug resistance late in the disease. We studied a drug resistance marker, P-glycoprotein (P-gp), in a total of 43 patients with monoclonal gammopathy. This group included eight with monoclonal gammopathy of undetermined significance (MGUS), five with plasmacytoma (PCM), nineteen with multiple myeloma (MM; six newly diagnosed, seven plateau, five refractory, one relapse) and eleven amyloidosis (seven newly diagnosed, four after treatment). Using 3-color flow cytometry, a plasma cell gate was selected on the basis of CD38+/45-(dim) staining and the population was examined for the expression of P-gp using two monoclonal antibodies (MRK16 and UIC2). P-gp expression was positive on marrow plasma cells in 42/43 patients. The resistance index (RI) in these cases (range 2.0-7.07) is comparable to that in the positive cell line KG-1A (3.05-3.08). In 2 of 5 patients with refractory MM, the RI for P-gp (5.4, 6.36) was higher than in plateau phase. These data suggest that relative resistance due to the P-gp mechanism is likely to be an intrinsic property of plasma cells in monoclonal gammopathies and may provide a partial explanation as to why these diseases always relapse. The results of our study support strategies for MDR reversal earlier in the course.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine.

BACKGROUND: Primary systemic amyloidosis is an uncommon disease characterized by the accumulation in vital organs of a fibrillar protein consisting of monoclonal light chains. METHODS: We treated 220 patients with biopsy-proved amyloidosis. The patients were randomly assigned to receive colchicine (72 patients), melphalan and prednisone (77), or melphalan, prednisone, and colchicine (71). They were stratified according to their chief clinical manifestations: renal disease (105 patients), cardiac involvement (46), peripheral neuropathy (19), or other (50). RESULTS: The median duration of survival after randomization was 8.5 months in the colchicine group, 18 months in the group assigned to melphalan and prednisone, and 17 months in the group assigned to melphalan, prednisone, and colchicine (P<0.001). Among patients who had a reduction in serum or urine monoclonal protein at 12 months, the overall length of survival was 50 months, whereas among those without a reduction at 12 months, the overall length of survival was 36 months (P=0.03). Thirty-four patients (15 percent) survived for five years or longer. CONCLUSIONS: Therapy with melphalan and prednisone results in objective responses and prolonged survival as compared with colchicine in patients with primary amyloidosis.

Aged↗

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

Prosthetic hip replacement for pathologic or impending pathologic fractures in myeloma.

The authors retrospectively reviewed 53 hip replacements performed in 50 patients (mean age, 65 years) for plasmacytoma (four lesions) or multiple myeloma (49 lesions) of the hip region. Perioperatively, 49 patients received chemotherapy. Twenty-four hip lesions had radiation therapy. Within a mean followup period of 32.6 months, 15 (28%) complications occurred. Late deep infection, dislocation, and aseptic loosening with medial migration of the acetabular component occurred in one patient each. Three patients died during the first postoperatively month. All of the remaining patients postoperatively regained their previous ambulatory status; hip pain relief was achieved in 98% of patients. At the time of the latest followup evaluation, 84% of the patients had died (median survival time, 18 months) and 16% were still alive (median survival time, 76 months). Patients with plasmacytoma had longer survival than did patients with multiple myeloma (median survival, 6.3 years versus 18 months, respectively). No significant association was found between patient survival and the stage of disease at diagnosis, age, gender, type or location of the myeloma lesion, or the type of implant used. Because of the relatively long survival time, prosthetic replacement is indicated for extensive hip lesions in patients with plasmacytoma or multiple myeloma.

Adult↗

PubMed1996

Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma.

The purpose of this study was to quantitate the number and labeling index of monoclonal plasma cells in the blood of patients with newly diagnosed multiple myeloma (MM) to learn if these values were independent prognostic factors for survival. Patients were candidates for this study if they had untreated myeloma requiring therapy, were evaluated at our institution between 1984 and 1993, and had a sample of blood analyzed with a sensitive immunofluorescence technique for monoclonal plasma cells and the blood B-cell labelling index (BLI). The % blood monoclonal plasma cells (%BPC) and the BLI were analyzed along with stage, marrow plasma cell LI, % marrow plasma cells, calcium, creatinine, albumin, beta-2-microglobulin, and C-reactive protein as univariate and multivariate factors for survival. Eighty percent of the 254 patients accrued to this study had monoclonal BPC detected. The median % BPC was 6% and 57% (144 of 254) of patients had a high number (> or = 4%). Patients with > or = 4% BPC had a median survival of 2.4 years vs 4.4 years for those with < 4% BPC (P < .001). The BLI was also prognostic (P = .008). In a multivariate analysis, the % BPC, age, albumin, stage, marrow plasma cell LI, and the BLI were independent factors for survival. The %BPC and the marrow plasma cell LI best separated the group into low, intermediate, and high risk myeloma with median survivals of 52, 35, and 26 months, respectively. Patients with high %BPC were less likely to have lytic bone disease from their MM (P = .002). The %BPC and the BLI are independent prognostic factors for survival and are useful in identifying patients as low, intermediate, and high risk. Clonal cells in the blood should be quantified in future clinical trials for myeloma.

Adult↗

PubMed1996

Multiple myeloma in patients younger than 30 years. Report of 10 cases and review of the literature.

OBJECTIVES: To analyze the presenting clinical and laboratory features and the outcome in a series of 10 patients younger than 30 years with multiple myeloma (MM) and to compare the findings with those reported in the literature. METHODS: The records of all patients younger than 30 years with MM who were seen at the Mayo Clinic, Rochester, Minn, between January 1, 1956, and December 31, 1992, were reviewed. RESULTS: The frequency of MM in patients younger than 30 years who were seen at the Mayo Clinic was 0.3%. The clinical and laboratory features were typical of MM in 7 of the 10 patients. Two patients with no increase in bone marrow plasma cells had extensive extramedullary involvement, along with multiple skeletal lesions and the presence of an M protein in the serum and urine samples. One patient had multiple lytic lesions and 10% bone marrow plasma cells with no M component until 6 years after diagnosis, when a sacral plasmacytoma developed and an IgA-kappa protein became apparent. Four patients had initial extramedullary involvement, 3 had renal insufficiency, and 2 had hypercalcemia. Osteolytic lesions were initially found in 6 patients. The M protein was light chain only in 5 patients and IgD in 2. Five patients responded to the initial conventional therapy, and 2 patients with primary resistant disease achieved long-lasting responses with high-dose therapy. The median duration of survival of the patients was 87 months. The proportion of patients who were predicted to be alive at 5 and 10 years was 69% and 31%, respectively. CONCLUSIONS: In very young patients with MM, the presenting findings and the response to conventional therapy are similar to those in patients of all ages who have MM. However, a high proportion of patients had light-chain and IgD myeloma, and 2 patients with primary resistant disease achieved long-lasting responses with high-dose therapy. The survival of our patients was considerably longer than that of patients of all ages with MM.

Adult↗

PubMed1996

Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma.

The blood of most patients with active multiple myeloma (MM) contains cells related to the bone marrow tumor. However, identifying clonal cells in the blood of patients with monoclonal gammopathy of undetermined significance (MGUS) has been difficult. In this study, we analyzed blood mononuclear cells (BMNCs) from 16 patients with MGUS, 2 with amyloidosis, 8 with smoldering MM (SMM), 2 with indolent MM (IMM), and 15 with active MM using three different methods to detect and quantitate clonal cells, ie, immunofluorescence microscopy (IM) for monoclonal plasma cells, three-color flow cytometry (FC) for CD38(+)CD45- CD45(dim) cells, and the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). Using ASO-PCR, we were able to detect clonal cells in the blood in 13 of 16 patients with MGUS, 2 of 2 with amyloid, 6 of 8 with SMM, 2 of 2 with IMM, and 13 of 15 with MM. In 9 of the 13 patients with MGUS with blood involvement, the number of clonal cells was very small ( < 0.04% of the BMNCs). The median percentage of clonal cells as determined by ASO-PCR was 0.02 for MGUS, 0.02 for SMM, and 0.24 for MM. Clonal plasma cells or CD38+CD45-CD45(dim) cells were identified by IM or FC in 6 of 16 MGUS patients, 4 of 8 with SMM, and 11 of 15 with MM. In all cases in which IM or FC detected clonal cells, the ASO-PCR was positive. This study shows that, by using ASO-PCR, clonal cells can be found at very low levels in the blood in most patients with MGUS. However, the number of clonal cells in the blood of MGUS patients is less than those with overt MM (P = .006). In contrast to MGUS, patients with active MM are more likely to have identifiable clonal circulating plasma cells (P = .05).

Alleles↗