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

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1108-1111
Author(s):  
MA Gertz ◽  
RA Kyle ◽  
PR Greipp
Keyword(s):  
Multiple Myeloma ◽  
Median Survival ◽  
Plasma Cell ◽  
Poor Prognosis ◽  
Systemic Amyloidosis ◽  
Labeling Index ◽  
Cell Labeling ◽  
Plasma Cell Dyscrasia ◽  
Response To Chemotherapy

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).

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

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1108-1111 ◽  
Author(s):  
MA Gertz ◽  
RA Kyle ◽  
PR Greipp
Keyword(s):  
Multiple Myeloma ◽  
Median Survival ◽  
Plasma Cell ◽  
Poor Prognosis ◽  
Systemic Amyloidosis ◽  
Labeling Index ◽  
Cell Labeling ◽  
Plasma Cell Dyscrasia ◽  
Response To Chemotherapy

Abstract 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).

Incorporation of the plasma cell labeling index into the international staging system of multiple myeloma: Impact on prognostic value

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 8591-8591 ◽  
Author(s):  
P. Kapoor ◽  
C. Snozek ◽  
C. L. Colby ◽  
D. R. Larson ◽  
J. A. Katzmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Prognostic Value ◽  
Staging System ◽  
Labeling Index ◽  
Cell Labeling ◽  
International Staging System

A high bone marrow plasma cell labeling index in stable plateau–phase multiple myeloma is a marker for early disease progression and death

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2522-2523 ◽  
Author(s):  
David P. Steensma ◽  
Morie A. Gertz ◽  
Philip R. Greipp ◽  
Robert A. Kyle ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Group Versus ◽  
Labeling Index ◽  
Cell Labeling ◽  
Plateau Phase ◽  
Bone Marrow Plasma ◽  
High Bone

Abstract The plasma cell labeling index (PCLI) is a measure of plasma cell proliferative activity and is an important prognostic factor in newly diagnosed multiple myeloma (MM). Occasionally patients have been observed with stable, plateau phase MM with minimal numbers of residual light-chain–restricted monoclonal plasma cells, but a high PCLI. No data are available on the outcomes for such patients. Data from 57 patients with plateau phase MM and a marrow PCLI of more than 1.0% were compared with 105 matched control patients with MM with a marrow PCLI of less than 1.0%. All patients had less than 10% total plasma cells on marrow aspirate and biopsy. The median time to progression and overall survival were 8 months and 20 months, respectively, in the high PCLI group versus 39 months and 56 months, respectively, in the low PCLI group (P < .0001). These findings suggest that a high PCLI in patients with apparently stable, plateau phase MM is an adverse parameter that may predict a short time to disease progression and death.

MYC Activation Is a Common Transformation Event in Myeloma and Associated with Poor Prognosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 834-834
Author(s):  
Wee-Joo Chng ◽  
Gaofeng Huang ◽  
Siok-Bian Ng ◽  
Marta Chesi ◽  
Leif Bergsagel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Plasma Cell ◽  
Poor Prognosis ◽  
Gene Set Enrichment Analysis ◽  
Labeling Index ◽  
Cell Labeling ◽  
Validation Dataset ◽  
Newly Diagnosed ◽  
Ras Mutation

Abstract Abstract 834 Multiple myeloma (MM) is an incurable bone marrow cancer. Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to MM is unknown. We analyzed 2 gene expression datasets generated on the Affymetrix U133 platform. The test set consisted of 22 MGUS and 101 MM (GEO Accession GSE6477) and the validation set 50 MGUS and 351 MM (GEO Accession GSE2658 and GSE5900). The gene expression profiles of MM were compared to MGUS using gene-set enrichment analysis. Genes over-expressed in MM were enriched for cell cycle, proliferation and MYC activation gene-sets. We dissected the relationship between MYC and cell cycle, and identified a MYC activation signature dissociated from proliferation. We validated our MYC signature in publicly available mouse and human cell line gene expression dataset (GEO Accession GSE3151 and GSE3158 respectively), showing specific expression of our MYC signature in cell lines forced to expressed MYC but not when over-expressing other oncogene such as E2F, HER2. In these analyses, we noted that tumors with RAS mutation also consistently express this signature. Applying this signature to the test dataset, we showed that MYC is activated in 60% of myeloma but none of MGUS. This pattern is reproduced in an independent validation dataset. In order to validate the hypothesis that RAS mutation may also lead to the MYC activation signature, we correlated RAS mutation with MYC activation as measured by a MYC index calculated from the median expression of genes that constitute the MYC activation signature, and showed that almost all cases with RAS mutation have a high MYC index. Together with samples with very high expression of MYC mRNA corresponding to those with MYC translocations, these 2 mechanisms account for 67% of cases with MYC activation. To further confirm MYC activation, we performed immunohistochemistry using a validated MYC antibody together with CD138 double-staining. We can clearly identify CD138 positive plasma cells with and without nuclear MYC expression and found that nuclear expression of MYC, a marker of MYC activation, correlated strongly with the MYC signature, therefore providing clear evidence that MYC activation is present in majority of newly diagnosed MM but not in MGUS. MYC activation is not very well correlated with proliferation as assessed by the plasma cell labeling index. Among newly diagnosed myeloma patients with plasma cell labeling index less than 1, those with nuclear MYC expression have significantly shorter survival than those without (Median survival 77.7 months versus 37.9 months, log-rank p-value 0.04). Multiple pathways converge on MYC activation, which is a common transforming event in MM associated with poor prognosis. MYC nuclear staining by IHC can be a useful clinical surrogate. Targeting MYC can be a chemoprevention strategy. Disclosures: Fonseca: Amgen: Consultancy; Medtronic: Consultancy; Celgene: Consultancy; Bristol Mayor Squibs: Consultancy; Genzyme: Consultancy; Otsuka: Consultancy.

Multiple myeloma: significance of plasmablastic subtype in morphological classification

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 305-310 ◽  
Author(s):  
PR Greipp ◽  
NM Raymond ◽  
RA Kyle ◽  
WM O'Fallon
Keyword(s):  
Multiple Myeloma ◽  
Renal Insufficiency ◽  
Median Survival ◽  
Plasma Cell ◽  
The Other ◽  
Cell Labeling ◽  
Morphological Classification ◽  
Kaplan Meier

Abstract We classified 100 cases of myeloma before chemotherapy as mature (28), intermediate (38), immature (19), or plasmablastic (15). The plasmablastic group had an estimated median survival (Kaplan-Meier method) of ten months, compared to 35 months for the other types (P less than .05). Decreased survival in the plasmablastic group was due to more frequent deaths in the first six months. There were no significant differences in survival among the mature, intermediate, and immature groups or among patients with different morphological grade or asynchrony scores. The plasmablastic myeloma group had more frequent renal insufficiency and higher plasma cell labeling indices, which may have contributed to the shorter survival.

scholarly journals Plasma Cell Labeling Index in the Evaluation of Smoldering (Asymptomatic) Multiple Myeloma

2010 ◽  
Vol 85 (3) ◽  
pp. 300 ◽  
Author(s):  
Sumit Madan ◽  
Robert A. Kyle ◽  
Philip R. Greipp
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Labeling Index ◽  
Cell Labeling

scholarly journals Clinical, morphological, and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 166-171 ◽  
Author(s):  
PR Greipp ◽  
RA Kyle
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Labeling Index ◽  
Cell Labeling ◽  
Linear Discriminant ◽  
Smoldering Multiple Myeloma ◽  
Undetermined Significance

We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.

MDR-1 expression and response to vincristine, doxorubicin, and dexamethasone chemotherapy in multiple myeloma refractory to alkylating agents.

1994 ◽  
Vol 12 (1) ◽  
pp. 115-119 ◽  
Author(s):  
J J Cornelissen ◽  
P Sonneveld ◽  
M Schoester ◽  
H G Raaijmakers ◽  
H K Nieuwenhuis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Plasma Cell ◽  
Multiple Drug Resistance ◽  
Labeling Index ◽  
Cell Labeling ◽  
Survival Duration ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Mdr 1

PURPOSE To assess whether the presence of enhanced multiple drug resistance (MDR)-1 gene expression in multiple myeloma (MM) patients predicts survival, as well as response to vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. PATIENTS AND METHODS Sixty-three MM patients refractory to alkylating therapy were studied. The presence of the MDR-1 gene product, a 170-kd glycoprotein (P-170), was analyzed in bone marrow plasma cells by means of the alkaline phosphatase (APAAP) technique using the P-170-specific monoclonal antibody (MoAb) C219. The prognostic value of MDR-1 gene expression, examined before VAD treatment, was compared with other established prognostic factors including beta 2-microglobulin, albumin, lactate dehydrogenase (LDH), and the plasma cell labeling index. RESULTS Fifty-nine percent of all samples were P-170-positive. No association could be demonstrated between response to VAD and MDR-1 gene expression (chi 2 P = .359), in contrast to high serum beta 2-microglobulin levels, which were positively correlated with response (P = .006). P-170-positive and -negative patients showed a median survival duration of 23 and 22 months, respectively, a difference that was not statistically significant (P = .9). beta 2-microglobulin, LDH, albumin, and the plasma cell labeling index were all significantly correlated with survival. CONCLUSION These results indicate that other mechanisms of resistance must be involved in MM apart from MDR. The role of MDR status at this stage of disease may be biased by the major contribution of dexamethasone to induction of response by VAD in MM patients.

scholarly journals Clinical, morphological, and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 166-171 ◽  
Author(s):  
PR Greipp ◽  
RA Kyle
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Labeling Index ◽  
Cell Labeling ◽  
Linear Discriminant ◽  
Smoldering Multiple Myeloma ◽  
Undetermined Significance

Abstract We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.

scholarly journals Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 518-521 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Plasma Cell ◽  
Initial Therapy ◽  
High Risk Group ◽  
Labeling Index ◽  
Cell Labeling ◽  
Risk Patients ◽  
Standard Risk

Abstract The outcome of patients with multiple myeloma is dictated primarily by cytogenetic abnormalities and proliferative capacity of plasma cells. We studied the outcome after initial therapy with lenalidomide-dexamethasone among 100 newly diagnosed patients, risk-stratified by genetic abnormalities and plasma cell labeling index. A total of 16% had high-risk multiple myeloma, defined by the presence of hypodiploidy, del(13q) by metaphase cytogenetics, del(17p), IgH translocations [t(4;14), or t(14;16)] or plasma cell labeling index more than or equal to 3%. Response rates were 81% vs 89% in the high-risk and standard-risk groups, respectively. The median progression-free survival was shorter in the high-risk group (18.5 vs 36.5 months, P < .001), but overall survival was comparable. Because of unavailability of all tests for every patient, we separately analyzed 55 stringently classified patients, and the results were similar. In conclusion, high-risk patients achieve less durable responses with lenalidomide-dexamethasone compared with standard-risk patients; no significant differences in overall survival are apparent so far. These results need confirmation in larger, prospectively designed studies.

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