scholarly journals Effect of MAGE-C1 Gene Expression on Prognosis and Effectiveness of Bortezomib-Containing Courses in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4327-4327
Author(s):  
Eleonora Makunina ◽  
Larisa Mendeleeva ◽  
Vadim L. Surin ◽  
Irina V. Galtseva ◽  
Julia O. Davidova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Serum Lactate ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Cell Content ◽  
Antitumor Response

Abstract Introduction. The group of genes, encoding cancer-testis antigens is actively studied as a new markers of refractory in some diseases, including multiple myeloma (MM). It is suggested that the MAGE-C1 gene in MM may be considered as an additional marker predicting the effectiveness of therapy. Purpose. Determine of MAGE-C1 gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) in MM patients and assess the correlation of expression with some laboratory parameters and response on bortezomib-containing therapy. Patients and methods. A prospective study from February 2019 to July 2021 included 76 MM patients (43 men and 33 women) aged 35 to 82 years (median 58). The level of MAGE-C1 gene expression by qPCR-PCR in bone marrow samples, enriched with CD138+ cells, was determined for all patients. Quantity of MAGE-C1 expression was calculated with 2ΔCt method relative to housekeeping gene expression. Plasma cell content ranged from 1 to 89% (median 26%), monoclonal paraprotein secretion vary from 2.1 to 82.1 g/l, Bence-Jones protein in urine (from trace values to 12.54 g/day) was determined in 50 patients. High - risk cytogenetic [t(4; 14)(p16; q32), del17p] was documented in 22 patients, bone plasmocytomas - in 36 patients, myeloma nephropathy - in 17. All patients recieved induction with bortezomib - containing courses. Median follow-up duration: 14 months (1-22 months). As a control, similar bone marrow cells of 7 healthy donors were investigated. Results. The average value of MAGE-C1 expression in donors was 0.01 ± 0.007, a range of values vary from 0.0003 to 0.06. Gene expression MAGE-C1 index > 0.06 is accepted as increased expression. High serum lactate dehydrogenase (LDH) level (higher than the upper limit of reference values) was observed in patients with high MAGE-C1 gene expression [median - 0.35], normal LDH-level (≤ 260 U/L) was observed in patients with lower MAGE-C1 gene expression [median - 0.04]; p < 0.0001 (Figure 1). Negative correlation was found between the content of hemoglobin (Hb) and level of MAGE-C1 expression: Hb ≥ 12.0 g/dl was observed in patients with increased MAGE-C1 expression [median - 0.27], and Hb 5.5-11.8 g/dl - in patients with lower expression indices [median 0.1]; p=0,034. Antitumor response was evaluated after induction therapy in 51 patients. In 100% of patients with MAGE-C1 expression of ≤ 0.06 ≥ partial response (PR) was achieved, while in patients with MAGE-C1 expression of 0.07-1.0 ≥ PR was achieved in 84.6% of cases, and in patients with MAGE-C1 expression of > 1.0 - in 58%; p > 0.05. Besides, patients with ≥ PR had a level of MAGE-C1 expression lower than patients with a refractory to bortezomib [median 0.17 vs 1.14]; p = 0.04 (Figure 2). Conclusions. High MAGE-C1 gene expression in MM patients is associated with an increase in LDH, which corresponds to stage III by R-ISS. Probability of achievement of the antitumor response ≥ PR on the bortezomib-containing induction is reliable above at patients with low MAGE-C1 expression while the hyperexpression of this gene is followed by a refractory to a bortezomib therapy. Further study of MAGE-C1 gene expression may promote a personalized approach in the choice of antitumor therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Role of Serum Lactate Dehydrogenase (LDH) As a Prognostic Marker for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3115-3115
Author(s):  
Krina Patel ◽  
Robert Z. Orlowski ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Lactate Dehydrogenase ◽  
Hematopoietic Stem Cell Transplantation ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Abstract 3115 Background: The International Staging System (ISS), chromosomal abnormalities, and response to therapy are well recognized predictors of outcome in multiple myeloma (MM). However, the role of serum lactate dehydrogenase (LDH) as a prognostic marker for MM is not well established. Recently we showed that high LDH at diagnosis of MM is a predictor of shorter survival. Here we report the impact of the LDH level at the time of autologous hematopoietic stem cell transplantation (auto-HCT) on its outcome. Methods: We evaluated 1,658 patients with symptomatic myeloma who underwent auto-HCT from July 1988 to December 2010 at our institution. The primary objective was to determine the impact of high LDH (>1000 IU/L) level, obtained on the start day of the preparative regimen, on progression free survival (PFS) and overall survival (OS). Results: Patient characteristics according to LDH level at auto-HCT are summarized in Table 1. Patients in the 2 LDH groups (>1000 or ≤ 1000) were matched for age, gender, disease status, and response to prior therapy at the time of auto-HCT. Patients with LDH >1000 IU/L had a significantly higher beta-2 microglobulin (β2m) and bone marrow plasmacytosis at the time of auto-HCT. Median times to neutrophil (10 vs. 10 days: p=0.10) and platelet engraftment (11.3 vs.12.2 days: p=0.20) were not different in the 2 groups. Also, there was no significant difference in CR, VGPR, PR or overall response rates between the 2 groups. Median follow up was 35 months (1 to 244). Median OS in patients with LDH >1000 and ≤ 1000 were 49.2 and 68.0 months, respectively (p=0.03). Median PFS in patients with LDH >1000 and ≤ 1000 were 14.4 and 24.7 months, respectively (p=0.001). On univariate analyses, >10% plasma cells in bone marrow biopsy, relapsed disease, serum β2M ≥ 3.5 at auto-HCT, presence of any chromosomal abnormality, and < PR after auto-HCT were associated with significantly shorter PFS and OS. Conclusions: Having a serum LDH value of >1000 IU/L prior to auto-HCT is associated with shorter PFS and OS in patients with MM. These high risk patients may require aggressive post-transplant therapy, including consolidation, maintenance, tandem transplants or novel approaches like immunotherapy. Disclosures: Shah: Celgene: Membership on an entity's Board of Directors or advisory committees.

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.

Clinical Significance of Immunoglobulin Isotype Switching in Patients with Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4980-4980
Author(s):  
Jae-Cheol Jo ◽  
Dok Hyun Yoon ◽  
Shin Kim ◽  
Kyoungmin Lee ◽  
Eun Hee Kang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Clinical Characteristics ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Isotype Switching ◽  
Immunoglobulin Isotype

Abstract Abstract 4980 Background: Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. However, immunoglobulin isotype switching (IS) has been reported during follow-up of patients with MM. Its clinical significance has not been established well. We aimed to evaluate the clinical characteristics of the patients with IS and outcomes in those patients in a single center cohort. Patients and Methods: A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and June 2012. We compared clinical characteristics and outcomes between those with and without IS. Results: Of the 377 patients, 34 (9%) demonstrated IS after a median 7. 9 months (range, 2. 2–95. 7 months) from diagnosis. These 34 patients with IS comprised 18. 2% (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3. 1% (7/229) of patients treated without ASCT (P<0. 001). Original immunological types were as follows: IgG (n=10), IgA (n=8), IgD (n=5), free kappa (n=4), and free lambda (n=7). Nine patients among them demonstrated second IS during follow-up. With a median follow-up times of 54. 1 months from the day of diagnosis in all study patients, the median OS has not been reached in patients with IS, and was 38. 3 months in patients with the absence of IS (P<0. 001). Multivariate analysis indicated that development of IS was a significantly favorable prognostic factor for predicting OS (Hazard ratio = 0. 19; 95% confidence interval = 0. 07–0. 53). ECOG PS 0–1 vs. 2–4, creatinine <2 mg/dL vs. ≥2 mg/dL, bone marrow plasma cells <50% vs. ≥50%, and ASCT done vs. not done were also independent prognostic factors for OS (P=0. 037, P<0. 001, P=0. 008 and P<0. 001, respectively). In the group of patients presenting with IS (n=34), differences in overall survival (OS) were not observed according to the timing of IS after diagnosis (<8 mo vs. ≥8 mo, P=0. 836), immunoglobulin isotypes (P=0. 176) and presence of second IS (P=0. 494), while ASCT was associated with longer survival (median OS; not reached vs. 65. 9 mo, P=0. 018). Conclusions: We confirmed higher frequency of IS in those who underwent ASCT and favorable prognosis in those experiencing IS. Its significance and underlying mechanism warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High serum lactate dehydrogenase predicts an unfavorable outcome in Chinese elderly patients with multiple myeloma

Oncotarget ◽  
2017 ◽  
Vol 8 (29) ◽  
pp. 48350-48361 ◽  
Author(s):  
Yan Gu ◽  
Ya-Hui Yuan ◽  
Ji Xu ◽  
Qing-Lin Shi ◽  
Xiao-Yan Qu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Elderly Patients ◽  
Serum Lactate ◽  
High Serum ◽  
Unfavorable Outcome ◽  
Serum Lactate Dehydrogenase ◽  
Chinese Elderly

Inflammasome and Autophagy Activation In Symptomatic Multiple Myeloma Could Predict Response To Thalidomide-Based Chemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3131-3131
Author(s):  
Fernando V Pericole ◽  
Adriana Silva Santos Duarte ◽  
Mariana Lazarini ◽  
Sara Teresinha Olalla Saad
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Inflammation ◽  
Clinical Data ◽  
Conflicts Of Interest ◽  
Inflammatory Cells ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Inflammatory Monocytes

Abstract The inflammasome is a protein complex activated by signals of cellular danger to trigger the innate immune defenses through the maturation of proinflammatory cytokines such as interleukin (IL)1β and IL18. Inflammasomes consist of pattern-recognition sensors (NLR family), adaptors (ASC), and effectors (caspase 1). IL1β initiates feedback loops through the IL1R-MyD88-NFκB pathway. Inflammasome activation promotes adaptive responses and limits reactive oxygen species (ROS) production. Autophagy is a cytoprotective pathway by which the cell sequesters damaged proteins and organelles for lysosomal degradation. The inflammasome is negatively regulated by autophagy and inflammasome activates autophagy. Inflammasome activity may play an important role in several nonmicrobial diseases with chronic inflammation, such as obesity, type 2 diabetes and cancer. We collected a cohort of diagnostic samples of total bone marrow (BM) from 31 MM patients, 3 plasma cell leukemia (PCL) patients and 9 healthy bone marrow donors (HD), together with clinical data. Four smoldering MM, 27 symptomatic MM and 3 PCL (2 primary and 1 secondary) were included. According to ISS, six patients were ISS I, 9 patients were ISS II and 16 were ISS III. We also stratified 18 of our symptomatic MM into groups according to response (CR/VGPR, PR, SD/PD). The offered treatment was thalidomide-based triplets. Essential genes from inflammasome (NLRP3, PYCARD, CASP1), pro-inflammatory interleukins (IL1B, IL18) and autophagy (BECN1, SQSTM1, MAP1LC3B) were verified by q-PCR. Gene expression was compared among subgroups and correlated with clinical data. CASP1 and PYCARD were increased in MM compared with HD, without differences among ISS subgroups. In PCL cases, CASP1 and PYCARD had lower expression when compared with MM, but did not differ from HD, confirming that PCL did not have inflammasome activation as MM did. NLRP3 was not different among all diagnostic subgroups. IL18 had decreased expression in PCL patients, compared with HD and MM. IL1B was not different among subgroups. PCL and MM had higher BECN1 expression compared with HD and these differences were also highlighted among ISS subgroups. SQSTM1 had increased expression in PCL, compared with HD and MM, but MM did not differ from HD. MAP1LC3B gene expression was similar among groups. A positive correlation was observed between CASP1 and PYCARD, IL1B and IL18, and between the three autophagic genes (BECN1, SQSTM1 and MAP1LC3B) as expected. BECN1 also correlated with IL1B and with CASP1; CASP1 and PYCARD correlated with BECN1 and SQSTM1, reinforcing the relation between autophagy and inflammasome. When the clinical data were analyzed, monocyte counts correlated with CASP1 and PYCARD; beta-2-microglobulin levels correlated with CASP1 and with NLRP3 and, finally, leukocyte and neutrophil counts correlated with IL1B, BECN1 and SQSTM1 BM expression levels. Analyzing response to thalidomide-based first line chemotherapy, VGPR/CR responders showed higher diagnostic NLRP3 expression (unpaired t test, P=0.03). The intricate interplay between autophagy and inflammasome has only recently been elucidated. Multiple myeloma is a B-cell neoplasm with great dependence of BM microenvironment. Inflammatory cells, especially monocytes and macrophages, are the main inflammasome activators, reducing ROS in the BM microenvironment. Autophagy is essential for plasmocytes, due to their high levels of intracellular proteins. Basal levels of autophagy in myeloma are high and are upregulated in response to ER stress and proteasome inhibition, protecting myeloma cells against apoptosis. Our results confirm the essential role of autophagy activation in myeloma. Interestingly, inflammasome activation in our cohort predicted a better response to thalidomide-based regimens and could be a novel response biomarker. Reinforcing our theory, recently thalidomide was described as an inhibitor of caspase 1 activation. Chronic inflammation is an established cancer hallmark and its role in myeloma pathogenesis seems to be important through inflammasome and autophagy dysfunction during disease progression, possibly creating dependency loops between inflammatory monocytes and neoplastic plasmocyte within the BM microenvironment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of esterase gene expression in multiple myeloma

2021 ◽  
Author(s):  
Romika Kumari ◽  
Muntasir Mamun Majumder ◽  
Juha Lievonen ◽  
Raija Silvennoinen ◽  
Pekka Anttila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Genomic Variation ◽  
High Expression ◽  
Genetic Profile ◽  
Esterase Gene ◽  
Low Expression

Abstract Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

scholarly journals Gas-Forming Pyogenic Liver Abscess with Septic Shock

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Muhammad S. Khan ◽  
Muhammad K. Ishaq ◽  
Kellie R. Jones
Keyword(s):  
Septic Shock ◽  
Liver Abscess ◽  
Clinical Course ◽  
Pyogenic Liver Abscess ◽  
Blood Stream ◽  
Serum Lactate ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Indirect Bilirubin ◽  
Serum Haptoglobin

The pyogenic liver abscess caused byClostridium perfringens(C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is itsα-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course ofC. perfringenssepticemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to considerC. perfringensinfection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature onC. perfringens.

Sign in / Sign up

Export Citation Format

Share Document