scholarly journals Novel Insight into Multi-Hit Multiple Myeloma Based on "Two-Hit" Theory of Cancer Causation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Chenxing Du ◽  
Xue-Han Mao ◽  
Jiahui Liu ◽  
Huishou Fan ◽  
Weiwei Sui ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Staging System ◽  
Hazard Ratio ◽  
Drug Induction ◽  
Double Hit ◽  
Definition Of ◽  
Standard Risk

Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Prognostic Significance of the Stage of Reaching MRD-Negative for Patients with Multiple Myeloma Received ASCT

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3945-3945
Author(s):  
Qian Sun ◽  
Juan Li
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Median Overall Survival ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Hematopoietic Stem ◽  
Three Stages ◽  
Standard Risk

Abstract Objective: To explore the prognostic significance of the stage of reaching MRD-negative for patients with newly diagnosed multiple myeloma (NDMM) patients who received autologous hematopoietic stem cell transplantation (ASCT). Methods: A retrospective analysis of 186 NDMM patients who received "induction therapy-ASCT-maintenance therapy" in our center and reached MRD-negative, according to the stage when the patient's MRD status turned negative (induction therapy, 3 months after ASCT, maintenance therapy) is divided into three stages, A, B, and C (Figure 1). We compared the clinical characteristics and prognosis of patients in the three stages. Results: The median time to progress (TTP) of 186 patients was not reached, the median overall survival (OS) was 113.8 months, and the median follow-up time was 67.6 months; the number of cases in the three stages of A, B, and C was 73 (39.2%), 42 (22.6%), and 71 (38.2%), respectively (Figure 2). The median TTP of the patients in the three stages was not reached (P=0.013), and the median OS was not reached, not reached, and 71.2 months, respectively (P=0.026). Among the 124 standard-risk cytogenetics patients, the median TTP of the three stages of patients was not reached (P=0.121), and the median OS was not reached, not reached, and 99.6 months, respectively (P=0.091) (Figure 3). Among the 38 high-risk cytogenetics patients, the median TTP of patients in the three stages were unreached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months (P=0.625) (Figure 4). Among the 157 R-ISS Ⅰ-Ⅱ patients, the median TTP of the three stages was not reached (P=0.174), and the median OS was not reached, not reached, and 99.6 months (P=0.186) (Figure 5). Among 29 cases of R-ISS Ⅲ, the median TTP of the 3 stage patients was unreached, unreached, and 35.1 months (P<0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020) (Figure 6). Conclusion: For the same patients with MRD negative, the prognosis of patients reaching MRD-negative at different stages is different. The stage of reaching MRD-negative can predict the prognosis of patients with R-ISS stage Ⅲ, but cannot predict the prognosis of patients with R-ISS Ⅰ-Ⅱ. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The Frequency of Genetic Anomalies According to Clonal Plasma Cells' Phenotype in Patients with Newly Diagnosed (ND) Multiple Myeloma (MM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5316-5316
Author(s):  
Andrei Garifullin ◽  
Irina Martynkevich ◽  
Sergei Voloshin ◽  
Alexei Kuvshinov ◽  
Ludmila Martynenko ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Risk Groups ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Definition Of ◽  
Standard Risk

Abstract Background. Genetic anomalies (GA) are primary link of pathogenesis in MM. GA lead to formation of clonal plasma cells, which has different phenotype. Aim. To estimate the incidence of GA and their correlation with clonal plasma cells' phenotype in patients with ND MM. Methods. We analysed 22 patients with ND MM (median age 57 years, range 38-80; male/female - 1:1.75). Cytogenetic analysis was performed on bone marrow samples using standard GTG-method. Metaphase FISH analysis was performed according to the manufacturer's protocol using DNA probes: LSI 13(RB1)13q14, IGH/CCND1, IGH/FGFR3, LSI TP53 (17q13.1). 8-color immunophenotypic by flow cytometry using antibody to CD45, CD38, CD138, CD56, CD19, CD20, CD27 and CD117 antigenes. Results. Translocation t(11;14) was detected in 3/14 (21.4%) patients, del(13q) - 2/14 (14.3%), t(11;14) - 3/14 (21.4%), hypodyploidy - 1/20 (5%), del(17р) - 0% patients. Clonal plasma cells' phenotype CD38+CD138+CD45- was detected in 100%. Expression CD56+ was revealed in 11/22 (50%) patients, CD19+ in 9/22 (40.9%), CD117+ in 5/22 (22.7%), CD20+ in 1/22 (4.5%), CD27+ in 1/22 (4.5%). The frequency of GA didn't depend on clonal plasma cells' phenotype and was 27.3%(3/11) in CD56+ phenotype, 23.8%(5/21) - CD20-, 23.8%(5/21) - CD27-, 23.5%(4/17) - CD117-, 23%(3/13) - CD19-, 22.2%(2/9) - CD19+, 20%(1/5) - CD117+, 18.2%(2/11) - CD56-, 0%(0/1) - CD20+, 0%(0/1) - in CD27+ phenotype. Patients of standard risk group according to mSMART 2.0 with GA had CD19-negative plasma cells' phenotype vs. CD19-positive phenotype in patients of intermediate and high-risk groups (p<0.05). 3-years overall survival in standard risk group with CD19- phenotype was 92,3%, CD19+ - 77,7% (p>0.05). Conclusion . Identification of GA, which has adverse forecast, correlates with CD19+ plasma cells phenotype. The combined definition of plasma cells phenotype and GA can improve the system of risk stratification in MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Correlation Analysis Between Serum Lactate Dehydrogenase and Prognosis in Old New Diagnosed Multiple Myeloma Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5637-5637
Author(s):  
Yahui Yuan ◽  
Yan Gu ◽  
Xiaoyan Qu ◽  
Qinglin Shi ◽  
Hua Bai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Staging System ◽  
Serum Lactate ◽  
Stage Ii ◽  
Stage Iii ◽  
Serum Lactate Dehydrogenase

Abstract 【Abstract】 Objective Multiple myeloma (MM) is a kind of plasma cell malignancy tumor with larger heterogeneity. Patient's survival varies greatly. This study retrospectively analyzed serum lactate dehydrogenase (LDH) in 107 cases of elderly MM patients, to discuss its correlation with other clinical indicators of MM and the prognostic significance. Methods 107 cases of elderly MM patients were selected from our hospital from July 2008 to January 2016 as the research objects, all of whom were above 60 years and were newly diagnosed. OLIPAS AU5400 fully automatic biochemical analyzer was used to assay serum LDH concentration, and prognosis analysis was carried out combined with patients' clinical data. On this basis, 73 cases of MM patients were given R-ISS staging. Results At primary diagnosis, about 9.4% patients had increased LDH (10/107), with the median follow-up time of 15 (1-88.5) months. Median overall survival (OS) was 52.5±6.9 months in normal LDH group, while 15.5±5.2 (months) in elevated LDH group, and there were statistically significant differences (p<0.001); Median progression free survival (PFS) was 24.0±3.5 months in normal LDH group, while 12.0±10.5 monthsin elevated LDH group, and there were statistically significant differences (p=0.008). Multiple factors analysis showed that LDH was an independent prognosis factor of elderly MM. Median OS of patients was 44 and 72 months (p=0.820) with stage II and stage III of ISS staging, while median PFS was 23 and 22 months (p=0.963); Median OS of patients was 44 and 22.5 months (p=0.308) with stage II and stage III of R-ISS staging, while median PFS was 24 and 14 months (p=0.105). Conclusions LDH is one of the important indicators for prognostic judgment of elderly MM patients. R-ISS staging based on LDH level is superior to the ISS staging system in prognostic judgment. Disclosures No relevant conflicts of interest to declare.

Three-drug versus two-drug induction therapy regimens for patients with transplant-eligible multiple myeloma

2013 ◽  
Author(s):  
Mohamed Kharfan-Dabaja ◽  
Taiga Nishihori ◽  
Tea Reljic ◽  
Mehdi Hamadani ◽  
Rachid Baz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Drug Induction

scholarly journals Three-drug versus two-drug induction therapy regimens for patients with transplant-eligible multiple myeloma

2016 ◽  
Author(s):  
Mohamed Kharfan-Dabaja ◽  
Taiga Nishihori ◽  
Tea Reljic ◽  
Mehdi Hamadani ◽  
Rachid Baz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Drug Induction

Metaphase Cytogenetics Adds to Gene Expression Profiling in the Identification of High Risk Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 114-114
Author(s):  
Guido Tricot ◽  
Fenghuang Zhan ◽  
Bart Barlogie ◽  
Yongsheng Huang ◽  
Jeffrey Sawyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prognostic Significance ◽  
Staging System ◽  
Treatment Modalities ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Prognostic Information

Abstract The International Staging System (ISS), based on B2-microglobulin and albumin levels at the time of diagnosis, has now generally been adopted as a new prognostic classification system for multiple myeloma (MM). While readily and widely applicable, ISS does not account for genetic disease features, such as metaphase (CA) and interphase fluorescence in situ hybridization (FISH) cytogenetic abnormalities, which when examined in the context of standard prognostic variables, confer higher hazards of relapse and disease-related death. Recently, gene expression profiling (GEP) uncovered the major prognostic significance for outcome of high expression of CKS1B, a gene mapping to an amplicon at chromosome 1q21. We have performed a comprehensive study of CA, FISH, GEP and ISS staging in 351 newly diagnosed MM patients, treated uniformly on Total Therapy 2. We have analyzed outcome based on a combination of high CKS1B by GEP and CA. GEP-based t(11;14) was prognostically favorable, irrespective of expression of CKS1B and, therefore, was removed from the group of patients with high CKS1B expression. After this adjustment, with the combination of both CA and high CKS1B (approximately 10% of all patients) conferred a very poor outcome with only 24% and 40% of such patients being event-free and/surviving at 3 years, compared with 72% and 84% for the others (p values : &lt;.0001). Such patients fared poorly, irrespective of their ISS stage. Similar prognostic information could be gained by combining CA with FISH-defined amplification of 1q21 and t(11;14). Because of their major prognostic impact, all newly diagnosed patients should be tested for these genetic markers. Novel treatment modalities are justified in the small subgroup of such poor prognosis patients, since they derive only a minor benefit from advances in MM therapy. CKS1B Q4 + CA (with no CCND1) vs. Others CKS1B Q4 + CA (with no CCND1) vs. Others

Cancer/Testis Antigens MAGE-C1/CT7 and MAGE-C2/CT10 Are Expressed in 90% of Multiple Myeloma Samples and Can Be Explored in Combined Immunotherapy for This Malignancy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4974-4974
Author(s):  
Fabricio de Carvalho ◽  
Veruska Lia ◽  
Fook Alves ◽  
Walter Moisés ◽  
Tobias Braga ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Responses ◽  
Plasma Cell ◽  
Conflicts Of Interest ◽  
Staging System ◽  
Cytotoxic T Cell ◽  
Malignant Neoplasms ◽  
Rt Pcr ◽  
Monoclonal Gammopathies ◽  
International Staging System

Abstract Abstract 4974 Background: Multiple Myeloma (MM) is a malignant proliferation of B-cells with plasma cell differentiation. Vaccines formulated with antigens associated with myeloma cells can instruct the immune system to eliminate malignant cells. Can/Testis Antigens (CTAs) tumor-associated antigens are identified in several human malignant neoplasms and in normal testis, fetal ovary and trophoblast cells. MAGE CTA genes are recognized by CTL (cytotoxic T cell) and are strictly tumor-specific. MAGE-C1/CT7 and MAGE-C2/CT10 are highly immunogenic and both CTAs have been previously shown in various human tumors, suggesting its potential role to evoke both humoral and cellular immune responses. Objective: We evaluated MAGE-C1/CT7 and MAGE-C2/CT10 expression in bone marrow (BM) aspirates collected from patients with MM, solitary plasmacytomas, MGUS (monoclonal gammopathy of undetermined significance) and normal controls to evaluate potential combination of CTA genes for immunotherapy in this disease by RT-PCR (reverse transcription-polymerase chain reaction). Material and Methods: BM aspirates from 20 MM patients [30% ISS (International Staging System) stage 1–2 and 70% stage 3], five solitary plasmacytomas, four MGUS and five normal BM aspirates. RNA was prepared from total BM aspirates using TRIzol, followed by synthesis of cDNA with SuperScript III, according to the manufacturer's instructions. MAGE-C1/CT7 and MAGE-C2/CT10 were analyzed by RT-PCR and 2% agarose gel electrophoresis and visualized by Sybr Safe. Results: MAGE-C1/CT7 was positive in 75% (15/20) and MAGE-C2/CT-10 in 70% (14/20) of MM cases. In 11 out of 20 MM cases (55%), both CTAs were positive and in 18 out of 20 samples (90%) the expression of at least one of the genes could be detected by RT-PCR. In the other monoclonal gammopathies (solitary plasmacytomas and MGUS), MAGE-C1/CT7 and MAGE-C2/CT10 were expressed in at least one of the analyzed cases. All BM aspirates collected from healthy donors were negative for both CTAs evaluated, showing restricted expression of these genes in monoclonal gammopathies. Considering the International Staging System (ISS), the data show that expression of both CTA genes were widely expressed in MM samples studied, independently on the stage of disease. Conclusions: These findings suggest that both MAGE-C1/CT7 and MAGE-C2/C10 CTA genes can have a biological role in MM distinct clinical phases and maybe contribute to malignant plasma cell development. The high frequency found in MM patients suggests that the subfamily of MAGE-C has a role on the development of myeloma. Although the function of these genes is still poorly understood, several studies have shown that MAGE-C1/CT7 and MAGE-C2/CT10 genes are able to elicit spontaneous immune responses; therefore they can be considered potential targets for cell therapy in this incurable disease. Disclosures: No relevant conflicts of interest to declare.

Multiple Copies of MLL Is The Most Commonly Detected Cytogenetic Abnormality In Newly Diagnosed Multiple Myeloma and May Modify Disease Risk

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1910-1910 ◽  
Author(s):  
Chrystal Landry ◽  
Dory Londono ◽  
Sean M. Devlin ◽  
Alex Lesokhin ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Protein Translation ◽  
Response To Therapy ◽  
Cytogenetic Abnormality ◽  
Newly Diagnosed

Abstract Background Multiple myeloma (MM) is a heterogeneous condition with variable disease course, response to therapy, and survival outcome. Cytogenetics and fluorescent in-situ hybridization (FISH) have identified several recurrent chromosomal aberrations in MM and play important and independent roles in risk stratification (Munshi et al. Blood 2011). However, the pathogenesis of the disorder remains poorly understood. Next-generation sequencing has recently identified that MM involves mutations of genes with roles in protein translation, histone methylation, and blood coagulation (Chapman et al. Nature 2011). Based on the observation that extra copies of MLL, a histone methyltransferase known to regulate the homeotic transcription factor HOXA9 that is highly expressed in MM, is frequently detected in MM, we sought to define the incidence and prognostic significance of excess MLL in MM patients. Methods We identified 188 patients with newly diagnosed MM who had cytogenetics and/or FISH performed on initial, pre-treatment bone marrow specimens at Memorial Sloan-Kettering Cancer Center between January 2009 and December 2012. Standard karyotype and FISH were performed as previously described (Cigudosa et al. Blood 1998, Gerritsen et al. Blood 1992). Probes included LSI IgH/FGF3, LSI IgH/CCND1, LSI IgH/MAF, LSI MLL, LSI p53/cep17, LSI13q14.3/13q34, LSI ETV6, LSI CBFB, LSI 1p36/1q25, and LSI 5,9,15 from Abbott Molecular. Fisher's exact test evaluated the association between MLL and selected abnormalities. Kaplan-Meier methodology estimated overall survival from the date of BM evaluation, and survival was compared using a logrank test. Results In unselected bone marrow specimens, abnormalities were detected by karyotype in 17% (27/156) and FISH in 47% (87/186) of patients tested. Hyperdiploidy, which has been associated with longer survival, was identified in 23% (43/187) of patients, while the unfavorable risk abnormalities, including loss of p53, deletion 13q (by karyotype), translocation (4;14) and excess 1q were seen in 8% (15/179), 8% (12/156), 4% (7/176) and 16% (29/178) of patients, respectively. Translocation (11;14) was seen in 4 patients; translocation (14;16) was not identified in any patient. 28% (51/183) of patients had extra copies of MLL, which was the most frequent genetic abnormality identified. Unexpectedly, this abnormality was significantly associated with both favorable (hyperdiploidy, P = <0.001) and unfavorable (deletion 13q, P = 0.043; excess 1q P = 0.001) risk genetics. While having excess MLL had no impact on the overall survival of standard-risk patients, defined as neither hyperdiploid nor with unfavorable genetics (N = 100), patients with poor-risk genetics (N = 46) and extra copies of MLL had a trend toward better survival, P = 0.06 (Figure 1). Conclusions Karyotype and FISH studies identified excess MLL as the most frequent cytogenetic abnormality in a large cohort of newly diagnosed MM patients. In patients with MM and unfavorable cytogenetics, the presence of excess MLL may ameliorate some of the adverse impact of associated with these abnormalities. Understanding the functional significance of excess MLL, perhaps as it relates to frequently dysregulated HOXA9 in MM, may provide insight into disease pathogenesis and/or identify drugable targets. Disclosures: No relevant conflicts of interest to declare.

The Expression Of CD200 As a Prognostic Factor In Newly Diagnosed Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3082-3082
Author(s):  
Yi Li ◽  
Wenjun Wu ◽  
Jingsong He ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Staging System ◽  
Newly Diagnosed ◽  
New Approach ◽  
Myeloma Cells ◽  
Targeting Therapy ◽  
Molecular Therapeutic

Abstract Introduction multiple myeloma (MM) is currently an incurable hematological malignancy. Discovering molecular therapeutic targets is a new approach to improve the outcome in the treatment of the malignant disease. As CD200 is a type Ⅰmembrane glycoprotein expressed on myeloma cells, we asked if the expression of CD200 could serve as a prognostic marker for MM patients. Our data indicated that the expression level of CD200 is indeed correlated with the prognosis of the MM patients. Methods bone marrow samples from 96 newly diagnosed MM patients from April 2011 to July 2013 were evaluated by flow cytometry, using PE-conjugated anti-CD200 mAb, FITC-conjugated anti-CD138 mAb, and PE-Cy7-conjugated anti-CD45 mAb. PE-or FITC-conjugated normal mouse IgG was used as isotype-matched controls. Results 96 MM patients were investigated in the present study, including 60 men and 36 women, with a median age of 63 years (range 34–86 years). 81/96(84%) MM patients were CD200 positive with a median Mean Fluorescence Intensity (MFI) of 127 as analyzed by flow cytometry, which was consistent with the previous studies. While in 15 of 96 patients, CD200 expression was undetectable. Among the CD200 positive ones 7.40% patients were classified as stage Ⅰ, 12.35% were stage Ⅱ, and 80.25% were stage Ⅲ according to Durie–Salmon staging criteria. 40.74% patients were stageⅠ, 22.22% were stage Ⅱ, and 37.04% were stage Ⅲ, according to the International Staging System (ISS). Analysis of the CD200 positive patients revealed the MFI<127 group had a better progression free survival (PFS) (p=0.046) (Fig 1A) and overall survival (OS) (p=0.069) compared to those with MFI≥127. In the patients with age ≥65 years old, PFS (p=0.023) (Fig 1B) and OS (p=0.044) (Fig 1C) were much shorter in the MFI≥127 group, compared to the MFI<127 ones. Conclusions Our study demonstrated that the expression and MFI of CD200 on primary multiple myeloma cells is correlated with the prognosis of the MM patients. The better PFS and OS were observed in the MFI<127 group compared to the patients with MFI≥127, especially in the patients with age≥65 years old. Improved PFS in CD200 positive ones is likely due to the immune suppression mediated by CD200. Our study suggests that targeting therapy against CD200 may become a new approach to the treatment of MM in clinical practice. Disclosures: No relevant conflicts of interest to declare.

Bortezomib-Based Chemotherapy Regimens Can Inmprove The Complete Remission In Newly Diagnosed Multiple Myeloma Patients With Bcl-2 and Survivin Overexpression

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5349-5349
Author(s):  
Zeng Wen ◽  
Huang Lifang ◽  
Yicheng Zhang ◽  
Sun Hanying ◽  
Liu Wenli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Staging System ◽  
Chemotherapeutic Agents ◽  
Tumor Burden ◽  
Newly Diagnosed ◽  
Double Positive ◽  
Research Fields

Abstract Compared with the traditional chemotherapeutic agents, Bortezomib-based chemotherapy regimens can increase the complete remission and improve the prognosis significantly in the newly diagnosed multiple myeloma patients. Molecular markers which can predict the chemotherapeutic efficacy and safety could help the physicians to make the right decisions and benefit the patients, and it has been one of most interesting research fields in MM. It has been reported that Survivin and Bcl-2 was involved in the adverse clinical events and therapeutic resistance, respectively. In order to investigate the relationship between the Survivin and Bcl-2 expression and the different regimens therapeutic efficacy, we retrospectively studied the proteins expression in the bone marrow biopsy specimens by inmmunohistochemistry and the efficacy of different chemotherapy regimens in the newly diagnosed MM in a single center of Tongji Hospital. Total 59 newly diagnosed MM were admitted into this study. The positive expression rate for Survivin and Bcl-2 was 35.3%（n=21）and 73.5%（n=43）, respectively. The protein expression had no relationship with the Durie-Salmon and International Staging System stratification, which suggested that Survivin and Bcl-2 were not responsible for the clinical manifestations. Bortezomib-based regimens (n=22) could effectively decrease the tumor burden and achieve response (CR+PR: 67.5% ). The non-bortezomib regimens (n=37), containing VAD(T), MP(T), TAD, were effective in the absent of Survivn and Bcl-2 expression(n=7; CR+PR 62.5% ). When Survivin and Bcl-2 were single or double positive (n=30), the newly diagnosed MM patients had no response for non-bortezomib regimens with none reaching complete remission or partial remission (p=0.0088). According to this study, we recommend the newly diagnosed MM which were Survivin and Bcl-2 single or double positive by inmmunohistochemistry received the regimens containing bortezomib for anti-myeloma therapy. Disclosures: No relevant conflicts of interest to declare.

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