Plasma cell labeling index, beta 2-microglobulin, and C-reactive protein: what is the best combination for myeloma prognosis? [letter; comment]

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.

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Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma [see comments]

Blood ◽

10.1182/blood.v81.12.3382.3382 ◽

1993 ◽

Vol 81 (12) ◽

pp. 3382-3387 ◽

Cited By ~ 230

Author(s):

PR Greipp ◽

JA Lust ◽

WM O'Fallon ◽

JA Katzmann ◽

TE Witzig ◽

...

Keyword(s):

Multiple Myeloma ◽

Prognostic Factors ◽

Thymidine Kinase ◽

Prognostic Significance ◽

Cell Labeling ◽

C Reactive Protein ◽

Prognostic Information ◽

Reactive Protein ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract 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.

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

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.1.115 ◽

1994 ◽

Vol 12 (1) ◽

pp. 115-119 ◽

Cited By ~ 51

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.

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Comparison of serum and synovial fluid concentrations of beta 2-microglobulin and C reactive protein in relation to clinical disease activity and synovial inflammation in rheumatoid arthritis.

Annals of the Rheumatic Diseases ◽

10.1136/ard.48.11.905 ◽

1989 ◽

Vol 48 (11) ◽

pp. 905-911 ◽

Cited By ~ 30

Author(s):

M T Walters ◽

F K Stevenson ◽

R Goswami ◽

J L Smith ◽

M I Cawley

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Disease Activity ◽

Synovial Inflammation ◽

Clinical Disease ◽

C Reactive Protein ◽

Clinical Disease Activity ◽

Reactive Protein ◽

Beta 2 ◽

Beta 2 Microglobulin

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Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma [see comments]

Blood ◽

10.1182/blood.v88.5.1780.1780 ◽

1996 ◽

Vol 88 (5) ◽

pp. 1780-1787 ◽

Cited By ~ 85

Author(s):

TE Witzig ◽

MA Gertz ◽

JA Lust ◽

RA Kyle ◽

WM O'Fallon ◽

...

Keyword(s):

Multiple Myeloma ◽

Prognostic Factors ◽

High Risk ◽

Plasma Cell ◽

Plasma Cells ◽

Cell Labelling ◽

Newly Diagnosed ◽

C Reactive Protein ◽

Reactive Protein ◽

Beta 2 Microglobulin

Abstract 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.

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

Blood ◽

10.1182/blood.v72.1.219.219 ◽

1988 ◽

Vol 72 (1) ◽

pp. 219-223 ◽

Cited By ~ 132

Author(s):

PR Greipp ◽

JA Katzmann ◽

WM O'Fallon ◽

RA Kyle

Keyword(s):

Prognostic Factor ◽

Creatinine Level ◽

Median Survival ◽

Plasma Cell ◽

Cell Labeling ◽

Enzyme Linked Immunosorbent Assay ◽

Significant Prognostic Factor ◽

Newly Diagnosed ◽

Beta 2 ◽

Beta 2 Microglobulin

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

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