| ObjectiveMultiple myeloma (MM) is a clonal plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein in the blood or urine, and associated organ dysfunction. It accounts for approximately 10% of all hematologic cancers. The conventional therapy results in lower response and MM is also incurable today. The clinical heterogeneity of MM is decided by multivariate factors. The traditional method to detect the proliferative activity of the tumor is hampered due to the hypoproliferative property of plasma cells in MM. The plasma cell labeling index (PCLI) is a powerful and independent predictor of survival in newly diagnosed MM which indicates plasma cell proliferative capacity. In this study, we detected the PCLI using a slide-based immunofluorescence method, and analyzed the prognostic value of PCLI in MM. We also studied its correlation with other known prognostic factors and clinical features.MethodThe PCLI was performed in using a slide-based immunofluorescence method, and the cutoff level for high PCLI was 1.0%. We analysis the correlation between PCLI and other prognostic factors or clinical features such as age, disease stage, bone marrow plasma cell percentage,β2-Microglobulin (β2-MG), serum albumin, C-reactive protein (CRP), lactate dehydrogenase (LDH), serum creatinine, and progression-free survival (PFS). ResultsWe studied 65 newly diagnosed MM patients, including 40 males and 25 females with a median age of 59 years (range, 33-76years). According to Durie and Salmon staging, 6 patients had stage I, 4 patients had stage II, and 55 patients had stage III. According to International Staging System, 8 patients had stage I, 32 patients had stage II, and 25 patients had stage III. The paraprotein was IgG in 34 patients, IgA in 16 patients, kappa light chain in 11 patients and lambda light chain in 4 patients. A high PCLI was observed in 26 patients (40.0%), a low PCLI was observed in 39 patients(60.0%), and the median level of PCLI is 0.51%(0-4.21%). Thereas was no correlation between PCLI and age, disease stage, bone marrow plasma cell percentage,β2-MG, serum albumin, CRP, LDH or serum creatinine. Whereas there was a strong correlation between PCLI and PFS, the patients with high PCLI had a shorter time to progression compared with the low PCLI group (median, 6.5 versus 15.5 month, P<0.05).ConclusionsMultivariable analysis showed that PCLI is a powerful and independent parameter of survival in newly diagnosed MM; the patients with a high PCLI have a poor prognosis and may predict a short time to disease progression and death. ObjectiveMultiple myeloma has very heterogeneous outcomes, its clinical heterogeneity is deceided by the biological characteristics, such as cytogenetic aberrations and plasma cell proliferative capacity. Cytogenetic studies in MM are hampered due to the hypoproliferative property of plasma cells in MM. Therefore, interphase fluorescence in situ hybridization (I-FISH) analysis combined with CD138 immunomagnetic cell sorting (MACS) is an attractive alternative for evaluation of numerical and structural chromosomal aberrations in MM. The plasma cell labeling index (PCLI) is a specific expression of plasma cell proliferative activity, and a high PCLI corresponds to a very short progression-free survival (PFS). It is very important to accurately evaluate the prognosis and to use risk-adapted therapy for patients with different MM. Our study is to investigate the incidence and prognosis of deletion of chromosome 13q14, 17p13 (TP53), illegitimate IGH rearrangements and PCLI in patients with MM; we also studied the PFS, overall survival (OS) and treatment efficiency of diffeient risk arms.MethodsMyeloma cells were enriched by MACS using the CD138 specific monoclonal antibody. Interphase FISH studies with three different specific probes for the regions containing 13q14(D13S319), 17p13(TP53) and 14q32(IGH) were performed in 65 MM patients. The probes of LSI IGH/CCND1, LSI IGH/FGFK3 and LSI IGH/MAF were used to detect t(11;14)(q13;q32), t(4;14)(p16.3;q32) and t(14;16) (q32;q23) in patients with 14q32 rearrangement. The PCLI was performed using a slide-based immunofluorescence method. According to the karyotype aberrations, PCLI and ISS stage, we divided the newly diagnosed patients into two groups: those with hyperdiploid or t(11;14) were considered to have standard-risk disease; and those with at least one of high risk features: hypodiploidy by conventional karyotyping; 13q14 deletion, 17p deletion, t(4;14) and t(14;16) by FISH; stageⅢof ISS or PCLI≥1%.ResultsAmong 65 newly diagnosed MM patients, 13q14 deletion was detected in 28 cases(43.1%), 17p13(TP53) deletion in 8 cases(12.3%), and IgH rearrangement in 36 cases(55.4%). Among 36 MM patients with IgH rearrangement, 16 (44.0%) cases harbored t(11;14), 13 (36.1%) cases harbored t(4;14), 5 (13.9%) cases harbored t(14;16), only two patients simultaneously had t(4;14) and t(14;16). PCLI≥1% was observed in 26 patients (40.0%), the PCLI had a significant correlation with del(13q14) (p=0.001), but there were no correlation between PCLI and other karyotype abnormalities. According to the risk Stractification study, 17 patients were in standard-risk, 48 patients were in high-risk. There were significant differences of median PFS between them (P=0.029). Patients with high-risk myeloma had shorter overall survival. However, there were no significant differences between them. Bortezomib could significantly improve the effects of complete remission (CR) and partial remission (PR) on MM patients with high-risk. It could also improve the rates of CR and PR on MM patients with standard-risk, but there were no significant differences between them. ConclusionsThe risk stratification study based on the molecular cytogenetic aberrations, plasma cell proliferative capacity and ISS can give a good guidance to the prognosis of MM patients. Bortezomib-based regimens results in better response rates and better outcomes in high-risk patients. |
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