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Multiple myeloma plasma cell labeling index detection and risk stratification system

Author: LiChunZuo
Tutor: ChenLiJuan
School: Nanjing Medical University
Course: Internal Medicine
Keywords: Multiple myeloma Plasma cell labeling index Prognosis Fluorescence in situ hybridization Risk stratification
CLC: R733.3
Type: Master's thesis
Year: 2011
Downloads: 27
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Abstract


The purpose of multiple myeloma (multiple myeloma, MM) is a malignant clonal proliferation of disease originated in the plasma cells, serum or urine monoclonal immunoglobulin (M protein) as well as multiple organ dysfunction characterized, accounting for blood 10% of the malignancies the conventional chemotherapy mitigation low so far difficult to cure. The clinical course presents a high degree of heterogeneity, a variety of factors MM prognosis. Plasma cell proliferative activity is low, the conventional method for detection of malignant proliferation of plasma cells in the degree of relative difficulty, specific reaction degree of proliferation of clonal plasma cells and plasma cell labeling index (plasma cell labeling index, PCLI), a separate newly diagnosed MM patients prognostic factors. In this study, the the immunofluorescence slides counting method detection MM patients the PCLI positive rate analysis of the prognostic value of PCLI of MM patients and correlation with other clinical prognostic indicators. The immunofluorescence slides count was detected in 65 patients with newly diagnosed MM patients PCLI to the cytoplasm light chain-specific nuclear staining cell count ≥ 1% as a positive standard, divided into positive and negative groups, analysis between the two groups with age, stage of disease, the number of bone marrow plasma cells, β2-microglobulin (beta2-MG), albumin, C-reactive protein (CRP) blood M protein, lactate dehydrogenase (LDH), and creatinine level differences, conduct univariate and multivariate analysis; further explore the two groups and no correlation progression-free survival (PFS). The results of 65 patients with previously untreated patients, 40 males and 25 females, with a median age of 59 years (33-76 years old). Durie-Salmon stage: Ⅰ of six cases, Ⅱ of four cases, Ⅲ 55 cases; ISS stage: 32 cases, 8 cases, Ⅱ I of III, 25 cases; M protein types: IgG 34 cases , IgA 16 cases, kappa light chain type 11 cases, the lambda light chain type 4 cases. 26 cases the PCLI positive group (40.0%), the PCLI negative group, 39 patients (60.0%); the PCLI median 0.51% (0-4.21%). Between the two groups in age, disease stage, there was no significant difference between the number of bone marrow plasma cells, β2-MG, CRP, albumin, LDH, creatinine levels. Analyze two groups with PFS significant correlation (P lt; 0.05), the PCLI positive and negative groups PFS were 6.5 months (0.5-42.5) and 15.5 (3.5-72.5) months, positive group PFS compared with negative group significantly shorter. Conclusion Multivariate analysis showed PCLI is an independent prognostic factor for judging patients with newly diagnosed MM; a high PCLI as an adverse prognostic factors, patients with short-term disease progression or death. Prognosis of the purpose multiple myeloma (MM) showed significant heterogeneity determined by their biological characteristics, such as cytogenetic abnormalities and malignant plasma cell proliferation degree. Conventional cytogenetics (CC) method detects chromosome abnormalities have some difficulties due to lower plasma cell proliferative activity using high purity bead sorting system (MACS) combined interphase fluorescence in situ hybridization (I-FISH) technology can be significantly improved the detection rate of MM molecular cytogenetic abnormalities; plasma cell labeling index (PCLI) specific reaction degree of malignant proliferation of clonal plasma cells, PCLI higher indicates a poor prognosis. The right to assess the prognosis of patients stratified treatment is extremely important. In this study, analysis of MM patients with 13q14 deletion 17p13 TP53 gene deletions, rearrangement of the immunoglobulin heavy chain (IgH) and the the PCLI disease incidence and prognostic significance; explore MM patients with standard-risk group and high-risk groups and clinical characteristics correlation between disease progression and efficacy. Separation method application the CD138 monoclonal bead antibody in patients with bone marrow, and then combined with interphase fluorescence in situ hybridization (I-FISH) were detected in 65 patients with newly diagnosed MM myeloma cells 13q14 deletion 17p13 (TP53 gene) missing IgH rearrangement in disease incidence. The IgH rearrangement-positive patients further LSI IGH / CCNDl probe to detect t (11; 14) (q13; q32) IGH/FGFR3 probe detection of t (4; 14) (p16.3; q32) IGH / MAF probe to detect t (14; 16) (q32; q23). By immunofluorescence slides count was detected in 65 patients with newly diagnosed MM PCLI. Karyotype abnormalities, plasma cell labeling index and ISS stage, we were divided into standard-risk and high-risk groups, defined as any of the following abnormal high-risk groups: chromosome 13 deletion, chromosome 17 deletion, t (4; 14), t (14; 16), hypodiploid, ISS stage Ⅲ, PCLI ≥ 1%; the rest of the standard risk group include: hyperdiploid, t (11; 14). Results Of the 65 patients with newly diagnosed patients, the the 13q14 deletion detection rate of 43.1% (28/65), 17p13 deletion detection rate of 12.3% (8/65), IgH rearrangement detection rate was 55.4% (36 / 65). Further analysis showed that 36 cases IgH rearrangement Sixteen patients (44.4%) for the t (11; 14) (q13; q32), 13 patients (36.1%) of the t (4; 14) (p16.3; q32) 5 cases (13.9%) t (14; 16) (q32; q23), including 2 patients with t (4; 14) (p16.3; q32) and t (14; 16) (q32; q23 ). 65 patients with previously untreated MM patients PCLI ≥ 1% detected in 26 cases (40.0%), PCLI 13q14 deletion has a significant correlation, while no significant correlation between other abnormal karyotype. Risk stratification, the standard-risk group of 17 patients, 48 ??cases of the high-risk group, the median PFS in the high-risk group was significantly lower than the standard risk group (P = 0.029), the difference was statistically significant; median OS of the high-risk group is also shorter than standard risk group, but the difference was not statistically significant; high-risk group than traditional chemotherapy remission rate with bortezomib-based chemotherapy, a statistically significant difference; standard risk group with bortezomib-based chemotherapy The response rate is also high, but the difference was not statistically significant. Conclusion Risk stratification of MM patients with high load indicators from the point of view of molecular genetics and tumor prognostic stratification a good guide their prognosis Analysis; early high-risk group should be adopted bortezomib-based chemotherapy, receive high quality mitigation and prognosis.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Bone marrow tumor
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