The biomechanics of vertebroplasty in multiple myeloma and metastatic bladder cancer: a preliminary cadaveric investigation

2008 ◽  
Vol 9 (5) ◽  
pp. 493-501 ◽  
Author(s):  
Robert J. Oakland ◽  
Navin R. Furtado ◽  
Jake Timothy ◽  
Richard M. Hall
Keyword(s):  
Multiple Myeloma ◽  
Bladder Cancer ◽  
Mechanical Behavior ◽  
Bone Metastases ◽  
Fracture Strength ◽  
Vertebral Column ◽  
Failure Strength ◽  
Metastatic Bladder Cancer ◽  
Increased Risk ◽  
The Impact

Object The vertebral column is the most common site for secondary bone metastases and lesions arising from hematological malignancies such as multiple myeloma (MM). These infiltrations can be lytic in nature and cause severe weakening of the vertebral body, an increased risk of fracture, and spinal cord compression leading to neurological deficit. Qualitatively it is apparent that increasing infiltration of these lytic lesions will have a deleterious effect on the mechanical behavior of the vertebrae. However, there is little quantitative information about the relationship between tumor deposits and the impact on the mechanical behavior of the vertebrae. In addition, there have been limited biomechanical assessments of the use of vertebroplasty in the management of these malignancies. The purpose of this preliminary study was to evaluate the mechanical behavior of lesion-infiltrated vertebrae from 2 malignant cancers and to investigate the effectiveness of vertebroplasty with and without tumor debulking. Methods Individual vertebrae from 2 donor spines—one with MM and another with bone metastases secondary to bladder cancer—were fractured under an eccentric flexion load, from which failure strength and stiffness were derived. Alternate vertebrae defined by spinal level were assigned to 2 groups: Group 1 involved removal of lesion material with Coblation (ArthroCare Corp.) preceding vertebroplasty; Group 2 received no Coblation prior to augmentation. All vertebrae were fractured postaugmentation under the same loading protocol. Micro-CT assessments were undertaken to investigate vertebral morphology, fracture patterns, and cement distribution. Results Multiple myeloma involvement was characterized by several small lesions, severe bone degradation, and multiple areas of vertebral shell compromise. In contrast, large focal lesions were present in the vertebrae with metastatic bladder cancer, and the shell generally remained intact. The mean initial failure strength of the vertebrae with metastases secondary to MM was significantly lower than in vertebrae with bone metastases secondary to bladder cancer (Load = 950 ± 300 N vs 2200 ± 750 N, p < 0.0001). A significant improvement in relative fracture strength was found postaugmentation for both lesion types (1.4 ± 0.5, p < 0.001). Coblation provided a marginally significant increase in the same parameter postaugmentation (p = 0.08) and qualitatively improved the ease of injection and guidance of cement. Conclusions In the vertebral column, metastatic lesions secondary to bladder cancer and MM showed variations in the pattern of infiltration, both of which led to significant reductions in fracture strength. Account should be taken of these differences to optimize the vertebroplasty intervention in terms of the cement formulation, delivery, and any additional surgical procedure.

The impact of race and sex on metastatic bladder cancer survival

Urology ◽  
2021 ◽  
Author(s):  
Amr Mahran ◽  
April Millera ◽  
Adam Calaway ◽  
Megan Prunty ◽  
Camilo Arenas-Gallo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Survival ◽  
Metastatic Bladder Cancer ◽  
The Impact

scholarly journals Metastatic Bladder Cancer Presenting with Persistent Hematuria in Young Man with Cystic Fibrosis

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Premal Patel ◽  
Harvey R. Rabin ◽  
Michael M. Vickers ◽  
Michael D. Parkins
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Bladder Cancer ◽  
Renal Colic ◽  
Atypical Symptoms ◽  
Metastatic Bladder Cancer ◽  
Increased Risk ◽  
Demographic Risk ◽  
Demographic Risk Factors ◽  
Rule Out

We report a case of metastatic bladder cancer developing in a young man with cystic fibrosis (CF) that was initially diagnosed as ureterolithiasis and managed as renal colic. With the improved survival of patients with CF, an increasing burden of extrapulmonary disease manifestations is apparent. Renal colic is observed at an increased frequency in patients with CF relative to the general population and is a commonly recognized cause of hematuria. However, CF patients harboring a malignancy are recognized to be at increased risk of delayed identification owing to atypical symptoms and lack of demographic risk factors. This case illustrates how investigations to rule out malignancy are warranted in those CF patients not responding to therapies directed towards presumptive diagnoses.

scholarly journals Bone Metastases Pattern in Newly Diagnosed Metastatic Bladder Cancer: A Population-Based Study

2018 ◽  
Vol 9 (24) ◽  
pp. 4706-4711 ◽  
Author(s):  
Chao Zhang ◽  
Lele Liu ◽  
Fang Tao ◽  
Xu Guo ◽  
Guowei Feng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Bone Metastases ◽  
Population Based ◽  
Newly Diagnosed ◽  
Population Based Study ◽  
Metastatic Bladder Cancer

Military Service in Vietnam/Korea and Serum Dioxin Levels Do Not Affect the Outcomes of Patients Diagnosed with Plasma Cell Dyscrasias

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5098-5098
Author(s):  
Prasanth Ganesan ◽  
Emil Kuriakose ◽  
Carla Smith ◽  
Robert T Harris ◽  
Jonathan E Dowell ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Military Service ◽  
Conflicts Of Interest ◽  
Military Veterans ◽  
Cell Transplant ◽  
Increased Risk ◽  
Plasma Cell Dyscrasias ◽  
Chlorinated Dioxins ◽  
The Impact

Abstract Abstract 5098 Military Service in Vietnam/Korea and Serum Dioxin Levels Do Not Affect the Outcomes of Patients Diagnosed with Plasma Cell Dyscrasias. Background: Exposure to dioxin, a contaminant found in herbicides has been associated with increased risk of cancers including multiple myeloma and postulated to cause poorer survival in the exposed population. Military personnel, especially those who had served in Vietnam and Korea have an increased risk of dioxin (which contaminated the herbicide Agent Orange which was sprayed during these wars) exposure. We looked at the impact of dioxin exposure and blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) which is the most toxic of the poly-chlorinated dioxins on the survival outcomes of military veterans diagnosed with plasma cell dyscrasias (PCD). Methods: A prospective analysis of newly diagnosed and existing myeloma patients was done. Information regarding the patient and disease characteristics, the military record, and outcomes were collected. Approximately 60 ml of heparinised peripheral blood was collected and immediately frozen at −20 degrees. These samples were shipped to Eurofins Laboratory, Hamburg, Germany for dioxin level measurement. Patients' blood lipid levels were also measured and the dioxin toxic equivalent (Teq) was calculated. Overall survival (OS) was calculated from the date of diagnosis till death (Kaplan Meier method). Cox regression and log rank analysis were used to look for prognostic variables. Results: Fifty two (52) patients of PCD were available for analysis. Majority had a diagnosis of multiple myeloma. Forty one underwent treatment including stem cell transplant in 16 (Table 1 shows the patient characteristics, laboratory results and treatment outcomes). During a median follow up of 54 months (2–348), 21 patients died (progressive myeloma: 12(23%), cardiac failure: 3 (5.7%), infections: 1 (1.9%), acute myeloid leukemia: 1 (1.9%), pulmonary embolism: 1 (1.9%) and unknown: 3 (5.7%). The median OS was 111 mos (95% CI 56–155) and the estimated survival at 5 yrs was 69.5% (+/− SE 0.067). The 5 yr OS was negatively impacted by abnormal cytogenetics (40.3 % vs. 75.5%; p=0.012), and service in the army (non-army vs. army: 83% vs. 40%; p=0.032). Patients who had served in Vietnam had outcomes similar to others; Korean War veterans had a poorer OS, but this was not statistically significant (5 yr OS 68% vs. 48%; p=0.1). There was no association between TCDD levels or the Teq with OS. Abnormal cytogenetics was the only significant factor on multivariate analysis. Conclusions: We did not find an association between military service in Korea/Vietnam or serum dioxin levels and poor survival in military veterans diagnosed with Plasma cell dyscrasias. However, a study of a larger sample of myeloma patients with similar service and exposure histories maybe warranted. Disclosures: No relevant conflicts of interest to declare.

Comorbidities Impact Survival in Multiple Myeloma: Analysis of the Veterans Health Administration National Database

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 760-760
Author(s):  
Tanya Wildes ◽  
Suhong Luo ◽  
Graham A Colditz ◽  
Kenneth R. Carson
Keyword(s):  
Cardiovascular Disease ◽  
Multiple Myeloma ◽  
Renal Impairment ◽  
Proportional Hazards ◽  
First Year ◽  
Risk Of Death ◽  
Increased Risk ◽  
Comorbidity Index ◽  
The Impact ◽  
Over Time

Abstract Abstract 760 Introduction: The incidence of multiple myeloma (MM) increases with age, and the prognosis worsens. Comorbidities increase in prevalence with age, yet little is known about the impact of comorbid medical conditions on outcomes in MM. Methods: In a retrospectively-assembled cohort study, all patients with MM diagnosed between 1998 and 2009 at a Veterans' Administration (VA) hospital were identified in the VA central cancer registry. Patients who received no treatment within 6 months of diagnosis were excluded, eliminating those with smoldering myeloma or who received supportive care only. Comorbidities were ascertained from ICD-9 codes present prior to the diagnosis of MM, and categorized using the Romano adaptation of the Charlson Comorbidity Index (CCI). The independent effects of age, race and comorbidities were examined using Cox proportional hazards modeling. The impact of individual comorbidities on survival was also examined, controlling for age and race. Results: A total of 2,968 patients were identified. The median age was 69 (range 27–92). The vast majority of patients (98%) were male; 28.6% of the patients were black. The median Charlson Comorbidity Index score was 2 (range 0–13). The frequencies of selected comorbidities were: diabetes (31%), renal impairment (23.8%), cardiovascular comorbidities (38.8%) and pulmonary (26.6%). The median overall survival (OS) for the entire cohort was 28.6 months at a median follow up of 26.8 months (range 0–137 months). On multivariate analysis, age was significantly associated with mortality [Hazard Ratio (HR) 1.03 per year (95% confidence intervals (CI) 1.03–1.04), p<0.0001]. Race was not significantly associated with survival [HR 0.99 (95% CI 0.90–1.09), p=0.81]. The median OS, adjusted for age and race, was 36.5 months for patients with no comorbidities, 33.9 months for patients with a CCI score of 1–2, 25.6 months for patients with a CCI score of 3–4 and 20.2 months for patients with a CCI score ≥5. The impact of comorbidities on survival violated the proportional hazards assumption, with a cut-point at 1 year, indicating that the influence of comorbidities varied over time. Relative to those with no comorbidities, the HR for death among those with a CCI score 1–2 was 1.20 (0.97–1.48) in the first year, and 1.03 (95% CI 0.89–1.18) subsequent to the first year; among those with a CCI score 3–4, the HR for death was 1.67 (95% CI 1.34–2.08) in the first year and 1.23 (95% CI 1.05–1.45) subsequently; among those with a CCI score ≥5, the risk of death in the first year doubled [HR 2.15 (95% CI 1.73–2.67)] and was increased 40% subsequently [HR 1.42 (95% CI 1.19–1.69)]. Individual prevalent comorbidities were then examined. Cardiovascular disease, renal impairment, and pulmonary disease were all significantly associated with mortality. In the first year after diagnosis, cardiovascular disease was associated with a 55% increase in mortality [HR 1.55 (95% CI 1.35–1.78)] while, subsequent to the first year, the risk was only increased about 20% [HR 1.19 (95% CI 1.07–1.39)]. The impact of renal impairment and pulmonary impairment did not vary over time; both were associated with a 25% increased risk of death [renal impairment HR 1.26 (95% CI 1.14–1.38); pulmonary disease HR 1.24 (95% CI 1.13–1.37)]. Diabetes was not associated with survival (HR 1.02, p=0.64) after controlling for age, race and cardiovascular, pulmonary or renal impairment. Conclusion: Age and comorbidities are independently associated with increased risk of mortality in MM. The influence of comorbidities varies over time, with the greatest impact noted in the first year after diagnosis of MM among those with a CCI score ≥3 and with cardiovascular disease. Further study is needed to determine whether this increased early mortality is related to increased risk of toxicity of therapy, inadequate MM therapy or both. Disclosures: No relevant conflicts of interest to declare.

Clinical and pathological outcomes for patients with T1HG bladder cancer managed with upfront cystectomy with or without neoadjuvant chemotherapy and the impact of the MDACC high-risk features.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 366-366
Author(s):  
Michael J. Metcalfe ◽  
James Edward Ferguson ◽  
Roger Li ◽  
Lianchun Xiao ◽  
Colin P.N. Dinney ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Systemic Disease ◽  
Survival Outcomes ◽  
Increased Risk ◽  
Node Positive Disease ◽  
Variant Histology ◽  
Muscle Invasive ◽  
The Impact

366 Background: In muscle invasive bladder cancer there is an increased risk for systemic disease identified for patients with certain high risk features (HRF): pre-operative hydronephrosis (POH), lymphovascular invasion (LVI), abnormal exam under anesthesia (AbnEUA), and the presence of variant histology (VH). We sought to identify the effect of these high risk features in the T1HG population. Methods: With IRB approval, a single center retrospective review was performed on all patients at MDACC from 1995-2013 who underwent radical cystectomy (RC) for T1HG urothelial cancer. Patients were stratified according to the presence or absence of HRF defined by the presence of LVI, POH, VH, AbnEUA, prostatic ductal involvement (PDI), and the delivery of neoadjuvant chemotherapy (NAC). Primary outcome included pathologic T (pT) upstage and presence of lymph node positive disease (LN+) at time of RC, as well as survival outcomes. Results: 372 T1HG patients underwent RC, of these 196 (53%) have HRF including: VH (n=98, 25%), LVI (n=44, 12%), PDI (n=31, 8%), POH (n=38, 10%) and/or AbnEUA (n=34, 9%). pT upstage occurred in 43/176 (24.4%) of patients without HRF, in 45/151 (30%) of patients with 1 HRF, and in 38% (17/45) of patients with > 2 HRF (p=0.088). LN+ occurred in 18/176 (10.2%) of patients without HRF, 7.8% (15/151) of patients with 1 HRF and in 17.8% (8/45) of patients with > 2 HRF (p=0.0403). Presence of HRF were not significant for a decreased OS (p=0.076), DSS (0.425), and RFS (p=0.103). No patients without HRF got NAC, and 41/196 (21%) of patients with HRF received NAC. There was no effect of NAC on pT upstage (OR 1.184, 95% CI 0.355-3.954, p=0.7834) or rate of LN+ disease (OR 1.758, 95% CI 0.669-5.606, p=0.2525) on multivariate analysis. There was no effect of NAC on OS (p=0.122), DSS (0.437), or RFS (0.7483). Conclusions: Presence of certain high risk features in the T1HG setting does have increased risk of pT upstage and LN+ disease in patients treated with cystectomy. However, there is no effect seen on survival outcomes. Use of NAC did not significantly alter outcome in our cohort and should be reserved for the muscle invasive setting.

scholarly journals Clinical Outcomes of COVID-19 in Hematological Malignancies in Jordan : Tertiary Cancer Center Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5039-5039
Author(s):  
Hazim Ababneh ◽  
Fadwa Alqadi ◽  
Mohammad ma'Akoseh ◽  
Khalid Halahleh ◽  
Layan abo Abed ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Outcomes ◽  
Hematological Malignancies ◽  
Polymerase Chain Reaction Test ◽  
High Morbidity ◽  
Icu Admission ◽  
Increased Risk ◽  
Anti Cancer ◽  
The Impact

Abstract Introduction: The COVID-19 infection has a devastating clinical outcome among individuals with immunocompromised states, particularly those with malignancies. The impact of the coronavirus pandemic on patients with hematological malignancies in low and middle-income countries is not well studied. Herein, we sought to report the clinical outcomes of the COVID-19 infection in patients with hematological malignancies treated at a single institution. Methods: Electronic medical record charts of patients diagnosed with hematological malignancies (leukemia, lymphoma, and multiple myeloma) were reviewed. Patients who were diagnosed with laboratory-confirmed SARS-CoV-2 infection by Real-Time Polymerase Chain Reaction test between April 2020 and October 2020 were identified as the subjects of this study. The demographic data, including tumor characteristics, laboratory results, anti-cancer treatments, patient outcomes (need for hospitalization, ICU admission, complications, and mortality), were extracted and analyzed. Results: We identified 89 patients diagnosed with hematological malignancies who were infected with COVID-19 during the eligibility period. The median age at the time of diagnosis was 54 years (range, 19-80 years). Fifty-two patients (58%) were male, and 37 patients (42%) were female. Of the 89 cases, 41 patients (46%) were diagnosed with lymphoma, 27 patients (30%) had leukemia, 21 patients (24%) had multiple myeloma. 84 patients (94%) received prior anti-cancer treatment, such as: chemotherapy (n=47, 53%), immunotherapy (n= 4, 4%), chemoimmunotherapy (n=26, 29%), and tyrosine kinase inhibitors (n=3, 3%). At the time of COVID-19 diagnosis, 52 patients (58%) had active malignancy, while 37 patients (42%) were in remission. Fifty-nine patients (66%) had comorbidities, with hypertension (n=32, 36%) being the most commonly reported comorbidity, followed by diabetes mellitus (n=25, 28%) and ischemic heart disease (n=8, 9%). The most encountered presentations were: fever (n=32, 36%) followed by cough (n=31, 35%), shortness of breath (n=21, 23%), aches (n=6, 7%), fatigue (n=6, 7%), and ageusia (n=6, 7%). Forty subjects (45%) were hospitalized, 11 patients (12%) were eventually admitted to the intensive care unit (ICU). Notably, the hospitalization and ICU admission rates were higher among the people aged more than 53 years (n= 24, 59%; n=9, 82%, respectively). Among the 89 patients, complications were recognized in 36% of the patients (n=32), with sepsis (n=12, 13%), acute kidney injury (n=11, 12%), and cardiovascular complications (n=3, 3%) being the most prevalent complications. The median time interval between the date of COVID-19 diagnosis and the last follow-up date was 3 months (range, 2 days-6.4 months). At the time of the last follow-up, 64 patients (72%) remained alive, and 25 patients (28%) succumbed to COVID-related complications. Conclusion: The COVID-19 infection has deteriorated clinical outcomes among patients with hematological malignancies, which could be attributed to the high incidence of infections, increased risk of hospitalizations/ICU admissions, and other COVID-related complications. Such high morbidity and mortality rates necessitate future studies to outline the potential risk factors for COVID-related complications and modifications in the plan of care, including evaluation of the effect of vaccination on the outcome of these patients. Disclosures No relevant conflicts of interest to declare.

Self-reported health and survival in older patients diagnosed with multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6582-6582
Author(s):  
Nadia Azmi Nabulsi ◽  
Ali Alobaidi ◽  
Brian Talon ◽  
Alemseged Ayele Asfaw ◽  
Jifang Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Medical Condition ◽  
Self Report ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Reported Health ◽  
Risk Of Cancer ◽  
The Impact

6582 Background: The strength of associations between pre-diagnosis self-reported health (SRH) and mortality differ by medical condition, with a moderately strong association reported among cancer patients. Less is known about the impact of SRH on survival among patients diagnosed with multiple myeloma (MM). We aimed to evaluate pre-diagnosis SRH in relation to survival in a cohort of older MM patients. Methods: We analyzed a prospective cohort from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) database of patients 65 years and older diagnosed with first primary MM. Survey responses to a single general health question (asking patients to self-report their health as excellent, very good, good, fair, or poor) were used to determine pre-diagnosis SRH, grouped as high (excellent/very good/good) or low (fair/poor). We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between SRH and risks of all-cause and cancer-specific mortality. Results: Of 521 MM patients with pre-diagnosis SRH data, the mean (SD) age at diagnosis was 76.8 (6.1) years with 60% of patients identifying as white, 18% as black, and 32% reporting low SRH. Compared to patients reporting high SRH, patients reporting low SRH were older, had lower education levels, more comorbidities, and lower Veterans-RAND 12 physical health and mental health component summary scores. In multivariable analyses, MM patients with low SRH had a 28% increased risk of all-cause mortality (HR = 1.28, 95% CI = 1.00, 1.64) and a non-statistically significant 19% increased risk of cancer-specific mortality (HR = 1.19, 95% CI = 0.87, 1.61) compared to MM patients reporting high SRH. Conclusions: Our findings suggest that lower SRH is highly prevalent among MM patients prior to diagnosis and is associated with modestly increased all-cause mortality. At a minimum, low SRH deserves clinical attention to determine how older MM patients’ quality of life may be compromised. The mechanism by which SRH affects mortality in MM should be further assessed and efforts should be made to identify whether any of the underlying mechanisms linking SRH and mortality in MM are mutable.

scholarly journals Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities

2020 ◽  
Vol 4 (15) ◽  
pp. 3509-3519 ◽  
Author(s):  
Nadine Abdallah ◽  
Patricia Greipp ◽  
Prashant Kapoor ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Characteristics ◽  
Tumor Burden ◽  
Disease Stage ◽  
Cytogenetic Abnormalities ◽  
Chromosome 1Q ◽  
Risk Of Death ◽  
High Tumor Burden ◽  
Increased Risk ◽  
The Impact

Abstract A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities in multiple myeloma (MM). It is unclear whether +1q is independently associated with decreased overall survival (OS). The objective of this study was to evaluate the impact of +1q on clinical characteristics, treatment response, and survival outcomes. We included 1376 Mayo Clinic patients diagnosed with MM from 2005 to 2018 who underwent fluorescence in situ hybridization testing at diagnosis with a panel including the +1q probe. A gain in 1q was found in 391 patients (28%) and was associated with anemia, hypercalcemia, high tumor burden, International Staging System (ISS) stage 3, high-risk (HR) translocations, and chromosome 13 abnormalities. There was no difference in overall response or deeper responses to proteasome inhibitor (PI)–, immunomodulatory drug (iMiD)–, or PI plus IMiD–based induction. Time to next treatment was shorter in patients with +1q compared with those without +1q (19.9 vs 27.7 months; P &lt; .001). On univariate analysis, +1q was associated with increased risk of death (risk ratio [RR], 1.9; P &lt; .001), and decreased OS was seen in all treatment groups. +1q was independently associated with decreased OS on multivariate analysis when other HR cytogenetic abnormalities, ISS stage 3, and age ≥70 years were included (RR, 1.5; P &lt; .001). Gain of &gt;1 copy of 1q was not associated with worse OS compared with gain of 1 copy (4.9 vs 4.3 years; P = .21). +1q was associated with high tumor burden, advanced disease stage, and HR translocations. It is independently associated with decreased OS, even in the setting of novel therapy and transplant.

scholarly journals The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (-8C>G) on the Development and Outcome of Multiple Myeloma

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
S. Zmorzyński ◽  
S. Popek-Marciniec ◽  
W. Styk ◽  
M. Wojcierowska-Litwin ◽  
I. Korszeń-Pilecka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Bone Marrow Cells ◽  
Risk Of Death ◽  
Automated Dna Sequencing ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Relationship Of ◽  
The Impact

Introduction. Multiple myeloma (MM) is a hematological malignancy characterized by genetic variety. The 3020insC variant of the NOD2/CARD15 gene results in the upregulation of proinflammatory cytokines. Chronic inflammation and abnormal function of the proteasome system may lead to MM development. The polymorphism (-8C>G) in the PSMA6 gene affects proteasome activity. The aim of our study was to analyze the possible relationship of NOD/CARD15 and PSMA6 genes with the risk of development and outcome of MM, as well as the sensitivity to bortezomib (proteasome inhibitor) in cell cultures derived from MM patients. Objects and Methods. Genomic DNA from 100 newly diagnosed MM patients and 100 healthy blood donors was analyzed by methods such as PCR-RFLP (for PSMA6 genotyping) and automated DNA sequencing (for NOD2/CARD15 genotyping). In a subgroup of 50 MM patients, nucleated bone marrow cells were treated with bortezomib in vitro. Results. Patients with PSMA6 CG+GG genotypes had higher chances for progressive disease (OR=5.0, 95% CI 1.07-23.16, p=0.05), shorter overall survival taking into account the type of treatment (p=0.039), and increased risk of death due to MM at the level of tendency (OR=4.74, 95% CI 1.02-21.97, p=0.06). The presence of NOD2/CARD15 3020insC decreased the risk of renal dysfunction in MM (OR=0.23, 95% CI 0.07-0.74, p=0.009). The analyzed changes in NOD2/CARD15 and PSMA6 genes did not impact the MM risk. In an in vitro study, bortezomib increased the number of apoptotic cells at 8 nM and 12 nM between wild-type and 3030insC variants of NOD2/CARD15 (p=0.018 and p=0.03, respectively). Conclusion. The presented results suggest a possible impact of PSMA6 CG+GG genotypes on the MM outcome and the association of the NOD2/CARD15 variant with bortezomib in vitro sensitivity.

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