The effect of high-dosed chemotherapy with support of autologous stem cell transplantation on proliferative and apoptotic characteristics of plasma cells
Authors:
V. Ščudla 1; M. Ordeltová 2; E. Faber 3; J. Minařík 1; T. Pika 1; J. Bačovský 1; N. Rytiková 4; K. Indrák 3; L. Dušek 5
Authors‘ workplace:
III. interní klinika Lékařské fakulty Univerzity Palackého a Fakultní nemocnice, Olomouc, 2Oddělení klinické imunologie Lékařské fakulty Univerzity Palackého a Fakultní nemocnice, Olomouc, 3Hematoonkologická klinika Lékařské fakulty Univerzity Palackého a
1
Published in:
Transfuze Hematol. dnes,16, 2010, No. 2, p. 92-100.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
In a cohort of 91 patients with multiple myeloma according to International Myeloma Working Group criteria, treated in 1996-2008 with high-dosed chemotherapy with support of autologous stem cell transplantation (HD-ASCT) and during progression/relapse also with novel biological drugs (thalidomide, bortezomib, lenalidomide), we compared the prognostic significance of the evaluation of kinetic properties of plasma cells. Both the parameters, i.e. proliferative and apoptotic index, were measured at the time of diagnosis and after the transplantation.Proliferative characteristics of myeloma plasmocytes were assessed with the use of propidium-iodide index (PC-PI), for the evaluation of apoptotic cells we used flow cytometry with the help of annexin-V FITC index (PC-AI). Myeloma plasmocytes were identified using the expression of CD138. We found that after HD-ASCT there was a statistically significant decrease in PC-PI with respect to initial measurements (average 2.5 vs 2.1, median (M) 2.4 vs. 2.1, p < 0.001) and an increase in PC-AI (average 5.4 vs 6.9, M – 4.8 vs. 5.6, p < 0,004) together with a decrease of summary index of proliferation and apoptosis (PC-PI/PC-AI) from the average value 0.69 and M 0.50 to 0.37 and 0.40 respectively, p < 0.001. It was revealed that the same results were within the assessment of PC-PI and summary PC-PI/PC-AI index in MM stages 1-3 according to Durie-Salmon (D-S) and International staging system (ISS). In the case of PC-AI there was a statistically significant increase in stage 3 patients and substage A according to D-S and stage 1 according to ISS. With the help of mathematical Kaplan-Meier model and log rank test we found that the median of overall survival (OS) from the time of diagnosis was in the whole cohort 85 months and from the date of HD-ASCT 74 months. Within the evaluation of all three indices (i.e. PC-PI, PC-AI and PC-PI/PC-AI) measured both at the time of diagnosis and after the HD-ASCT there was no relationship to OS. The presented analysis indicates that the use of HD-ASCT and novel biological agents lead to the loss of prognostic potential of both PC-PI and PC-AI indices, which was previously described in conventional therapy patients.
Key words:
multiple myeloma, propidium-iodide index, annexin-V index, proliferation, apoptosis, clinical stage, autologous stem cell transplantation, prognosis
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