Plasma cell acid phosphatase activity as prognostic factor in multiple myeloma: relationship to the thymidine-labeling index.

1985 ◽  
Vol 3 (11) ◽  
pp. 1503-1507 ◽  
Author(s):  
M Boccadoro ◽  
A Gallamini ◽  
A Fruttero ◽  
P Gavarotti ◽  
V Redoglia ◽  
...  

Plasma cell acid phosphatase (AP) activity and thymidine labeling index (LI%) were evaluated concomitantly in 52 patients with monoclonal gammopathies. AP score, percentage of AP positive plasma cells, and LI% were significantly higher in 26 patients with multiple myeloma (MM) at the time of diagnosis than in 11 monoclonal gammopathy of undetermined significance (MGUS) and eight smoldering myeloma (SM) patients. LI% had the highest statistical correlation with disease status. A 1% cutoff could clearly separate the patients with progressive MM compared to those with stable disease (SM-MGUS) (P less than .001). There was a significant overall correlation between the AP score and LI% (P less than .005). Since LI% is a recognized powerful prognostic factor, this correlation suggests that the AP score can also be a reliable test predicting patient survival duration. In addition, we identified a subgroup of IgG MM patients with very high tumor mass who had a low LI% but a high AP score. This was associated with very poor patient survival and indicated the discrete prognostic importance of AP score in this subgroup with low LI%. Thus, both the LI% and AP score can be recommended as helpful clinical tests in patients with monoclonal gammopathies.

1985 ◽  
Vol 59 (1) ◽  
pp. 67-72 ◽  
Author(s):  
J. J. M. L. Hoffmann ◽  
W. P. M. Breed ◽  
N. Swaak-Lammers

1994 ◽  
Vol 14 (5-6) ◽  
pp. 497-501 ◽  
Author(s):  
Pellegrino Musto ◽  
Saverio Fusilli ◽  
Mario Carotenuto

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3281-3287 ◽  
Author(s):  
SM Saeed ◽  
D Stock-Novack ◽  
R Pohlod ◽  
J Crowley ◽  
SE Salmon

Abstract In 1982 a randomized trial of either alternating or syncopated VMCP/VBAP regimens for the treatment of active multiple myeloma was begun (Southwest Oncology Group Study 8229/30). A concurrent investigation was undertaken to evaluate the clinical importance and significance of cytochemically stainable plasma cell acid phosphatase (AP) and beta-glucuronidase enzymes (BG). Pretreatment bone marrow aspirates were available for analysis from 399 patients for AP and 398 patients for BG. The AP scores ranged between 42 and 395, and the BG scores ranged between 1 and 346. There was a significant increase of AP (P = .001) and BG (P = .002) in multiple myeloma as compared with a set of patients with benign plasmacytosis. The enzyme scores did not significantly relate to Ig idiotype of myeloma or other prognostic variables except that the BG scores varied significantly with the level of albumin (P = .03) and hemoglobin (P = .01). Analysis of patient groups with different levels of enzyme scores showed that 61 of 398 patients with an AP score of less than 130 had a poorer median survival of 1.7 versus 2.8 years for patients with higher scores (P = .001). In the multivariate analysis of survival, low AP score was an important prognostic factor (P = .006), but BG did not contribute significantly. It is suggested that the subset of patients presenting with low AP should be considered for specialized or more aggressive therapy.


1994 ◽  
Vol 12 (1) ◽  
pp. 115-119 ◽  
Author(s):  
J J Cornelissen ◽  
P Sonneveld ◽  
M Schoester ◽  
H G Raaijmakers ◽  
H K Nieuwenhuis ◽  
...  

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.


Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3281-3287
Author(s):  
SM Saeed ◽  
D Stock-Novack ◽  
R Pohlod ◽  
J Crowley ◽  
SE Salmon

In 1982 a randomized trial of either alternating or syncopated VMCP/VBAP regimens for the treatment of active multiple myeloma was begun (Southwest Oncology Group Study 8229/30). A concurrent investigation was undertaken to evaluate the clinical importance and significance of cytochemically stainable plasma cell acid phosphatase (AP) and beta-glucuronidase enzymes (BG). Pretreatment bone marrow aspirates were available for analysis from 399 patients for AP and 398 patients for BG. The AP scores ranged between 42 and 395, and the BG scores ranged between 1 and 346. There was a significant increase of AP (P = .001) and BG (P = .002) in multiple myeloma as compared with a set of patients with benign plasmacytosis. The enzyme scores did not significantly relate to Ig idiotype of myeloma or other prognostic variables except that the BG scores varied significantly with the level of albumin (P = .03) and hemoglobin (P = .01). Analysis of patient groups with different levels of enzyme scores showed that 61 of 398 patients with an AP score of less than 130 had a poorer median survival of 1.7 versus 2.8 years for patients with higher scores (P = .001). In the multivariate analysis of survival, low AP score was an important prognostic factor (P = .006), but BG did not contribute significantly. It is suggested that the subset of patients presenting with low AP should be considered for specialized or more aggressive therapy.


Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 471-476
Author(s):  
V Hofmann ◽  
SE Salmon ◽  
BG Durie

In multiple myeloma, tumor cell mass and labeling index correlate with subsequent survival duration, but do not predict for response to treatment. In the present study was have autoradiographically measured the incorporation of 3H-thymidine as determined by the number of grains over the myeloma nuclei in bone marrow aspiration samples. In 33/37 patients with less than 50% tumor regression or progressive disease, the pretreatment grain count was greater than or equal to 20/myeloma nucleus. Conversely, values of less than 20 were found in 27/29 patients who had greater than or equal to 50% cell mass reduction. Survival duration was significantly better than (p less than 0.001) in patients with grain counts less than 20. Sixty percent of the patients with both a low labeling index (less than or equal to 3%) and grain count (less than 20) were alive at 48 mo, whereas 15/17 patients with a high labeling index and grain count had a median survival of less than 6 mo. In a subset of 22 patients, there as a significant correlation between in vitro resistance to melphalan, adriamycin, and vincristine as tested in the myeloma stem cell colony assay system and a grain count of greater than 20. We can only speculate as to the reasons for the increased 3H-thymidine uptake by myeloma cells resistant to treatment, however, it could be associated with accumulation of excess DNA and /or increased unscheduled DNA synthesis following injury from alkylating agents.


Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 471-476 ◽  
Author(s):  
V Hofmann ◽  
SE Salmon ◽  
BG Durie

Abstract In multiple myeloma, tumor cell mass and labeling index correlate with subsequent survival duration, but do not predict for response to treatment. In the present study was have autoradiographically measured the incorporation of 3H-thymidine as determined by the number of grains over the myeloma nuclei in bone marrow aspiration samples. In 33/37 patients with less than 50% tumor regression or progressive disease, the pretreatment grain count was greater than or equal to 20/myeloma nucleus. Conversely, values of less than 20 were found in 27/29 patients who had greater than or equal to 50% cell mass reduction. Survival duration was significantly better than (p less than 0.001) in patients with grain counts less than 20. Sixty percent of the patients with both a low labeling index (less than or equal to 3%) and grain count (less than 20) were alive at 48 mo, whereas 15/17 patients with a high labeling index and grain count had a median survival of less than 6 mo. In a subset of 22 patients, there as a significant correlation between in vitro resistance to melphalan, adriamycin, and vincristine as tested in the myeloma stem cell colony assay system and a grain count of greater than 20. We can only speculate as to the reasons for the increased 3H-thymidine uptake by myeloma cells resistant to treatment, however, it could be associated with accumulation of excess DNA and /or increased unscheduled DNA synthesis following injury from alkylating agents.


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