Plasma Cell Proliferation Using Ki67 Antigen Expression Defines Subgroups Related to Short Survival in Multiple Myeloma Especially with Low Beta-2 Microglobulin.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5031-5031
Author(s):  
Thomas Gastinne ◽  
Xavier Leleu ◽  
Anne-Sophie Moreau ◽  
Joris Andrieux ◽  
Jean-Luc Lai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Median Survival ◽  
Plasma Cells ◽  
Staging System ◽  
Stage I ◽  
Routine Practice ◽  
Ki 67 ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Abstract Background: The current most powerful prognosis model in Multiple Myeloma (MM) combines beta-2 microglobulin (b2m) with albumin, corresponding to the International Staging System (ISS). However, the prognosis of patients within the group I of ISS (high albumin and low b2m) may vary. Proliferative activity of plasma cells has been previously related to prognosis in MM, but methods proposed so far are difficult to apply in routine practice. Ki-67 is a nuclear protein associated with cell proliferation, and its expression is reported as a powerful prognosis marker in solid tumours and several hematological malignancies. We retrospectively evaluated the % of bone marrow plasma cells (BMPC) expressing Ki-67 antigen (Ki67 index) in a series of 174 untreated patients with MM at diagnosis and we looked for its prognostic value on survival in MM. Method: Ki-67 index was determined after double immunocytochemistry on PC from BM cytospins (ABC peroxidase to identify cells expressing Ki-67, and alkaline phosphatase to identify PC expressing either Kappa or Lambda light chain). Conventional cytogenetic study and interphase FISH (research of Rb1 gene deletion) were performed in 114 and in 128 pts respectively. Results: Median survival (± se; months) for pts with stage III, II, and stage I of ISS score were 20 (± 3), 41 (± 3), 51 (± 3) months, respectively (p<0.001). Median Ki-67 index (± se) was of 3.0% (± 1.2), 6.1% (± 1.2), and 6.5% (± 1.4) in ISS stage I, stage II, and stage III patients, respectively (p< 0.004). Independently of the ISS staging system, Ki-67 index ≥ 4% was highly predictive of adverse prognosis, with a median survival of 26 ± 4 months and of 49 ± 10 months over and under that value, respectively (p < 0.0001). B2m (threshold at 3 mg/L) gave identical results than Ki-67 index (p < 0.001), whereas chromosome 13 deletion (del 13) was less powerful (p< 0.02). Ki-67 index correlated well with several markers of intrinsic malignancy, with markers of tumour burden, but it was unrelated to age, serum creatinine and b2m. There was a strong relationship between hypodiploidy and BMPC proliferation: within the group of pts displaying Ki-67 index ≥ 4%, 93% pts were found hypodiploid (p < 0.0001). Within ISS stage I, median survival [± se; RR of death (95%CI)] was of 31 ± 4 months [2.65 (1.5–4.6)] and of 67 ± 6 months in patients with Ki-67 index ≥ 4% and < 4%, respectively (p < 0.001). Chromosome 13 deletion also delineated two groups within ISS stage I pts, but the difference did not reach statistical significance (p = 0.243). Finally, the combination of Ki-67 to b2m produced an efficient prognostic model that appeared the most effective in our series compared to known models such as b2m/chr 13 deletion and ISS. The -2Log (likelihood) scores calculated on 155 patients were 1107.885, 1113.256 and 1116.829 for Ki-67/b2m model, ISS model and b2m/del13 model, respectively. Conclusion: Ki-67 index is easy to perform in routine practice, and is a good prognostic marker, which provides additional survival prognostic information to b2m into the ISS model.

Impact of Serum Albumin and B2-Microglobulin level on 2-Year Overall Survival among Newly Diagnosed Multiple Myeloma Patients: A retrospective Study

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Sherian Salama ◽  
Rodaina Yousef ◽  
Asma Al Olama ◽  
Mahmoud Marashi ◽  
Hana Salama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Serum Albumin ◽  
United Arab Emirates ◽  
Staging System ◽  
Albumin Level ◽  
Age At Diagnosis ◽  
Newly Diagnosed ◽  
International Staging System ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Background: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Evaluation and initial staging of the disease is made once the diagnosis is confirmed. The recommended staging system is the International Staging System (ISS). Which determines the Myeloma prognosis by 2 factors: beta-2 Microglobulin and Serum albumin. Goal and Objective: The main goal of this study is to assess the effect of Beta-2 microglobulin and Serum albumin on patient’s survival rate with Multiple Myeloma. The secondary objective is to compare the age at diagnosis with other literature. Methodology: The current study was carried out in Hematology Unit, Dubai Hospital, Dubai, Dubai Health Authority (DHA), United Arab Emirates. Chart review was done retrospectively for 49 newly diagnosed patients with Multiple Myeloma diagnosed between the period 2012-2016. Purposive sample was used to those patients who met the inclusion criteria of this study, to be diagnosed and treated in DH. diagnosed and received regular treatment in Dubai Hospital. Results: Medina follow-up of the patients in this study was (12.8) months. The 2-year overall survival rate for patients with Multiple Myeloma (n = 49) was approximately 80%. While, the 2-year OS rate based on Albumin level. Patients with albumin level > 3.5 mg\dl was significantly higher compared to those who had an albumin level <3.5 mg\dl. 100%, 65% respectively, P = 0.033. Moreover, the 2-year OS rate in terms B2MG level. Patients who had a B2MG < 3.5 mg\dl OS was slightly higher compared to those who had (3.5-5.5 and 5.5 mg\dl). OS rate approximately 85 %, 80 % and 75 respectively, P = .737 Conclusion: Multiple myeloma (MM) is a very heterogeneous disease. For this reason, various prognostic factors and staging systems have been developed to predict the disease outcome. International Staging System (ISS) is very useful in determine the survival based on serum β2- microglobulin and serum albumin levels. The age at diagnosis in Dubai hospital, United Arab Emirates is much younger compared to other studies conducted worldwide. The sample used in the study was also highly diverse in terms of culture and nationality. Such diversity is largely typical in Gulf especially in United Arab Emirates. Therefore, this can play important role in age at diagnosis.

Clarithromycin (Biaxin®), Low Dose Thalidomide and Dexamethasone (BLT-D) in Newly Diagnosed and Previously Treated African American Patients with Multiple Myeloma: A Retrospective, Single Institution Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3501-3501
Author(s):  
Jack Jacoub ◽  
Joao L. Ascensao ◽  
Boyer James ◽  
Thomas O’Connor ◽  
Reema Batra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
Partial Response ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Staging System ◽  
Stage I ◽  
M Protein ◽  
Duration Of Treatment ◽  
Previously Treated

Abstract Introduction : African-Americans (AA) are twice as likely to develop multiple myeloma (MM) than Caucasians but are largely underrepresented in clinical trials. Thalidmode plus dexamethasone is an established therapy in MM. Biaxin® may augment the efficacy of this combination possibly via potentiating steroid activity (M. Coleman, et al. Leuk Lymphoma 2002, R. Niesvizky, et al. Blood 2003, Abs #832). Methods : We conducted a retrospective review of all AA patients (pts) with symptomatic MM treated with BLT-D from 2002-present. Treatment consisted of Thalidomide 50–200mg daily, Biaxin 500mg twice daily and dexamethasone 40mg weekly. All pts received monthly bisphosphonate therapy and aspirin 81–325mg daily. Response criteria was defined as follows: complete response (CR) = no detectable M-protein, marrow plasma cells &lt;5%; very good partial response (VGPR) = decrease in M-protein by &gt;90%; partial response (PR) = decrease in M-protein by &gt;50%; stable disease (SD) = M-protein decrease by &lt;50% without clinical progression; no response (NR)= progression with no change or increase in M-protein or response &lt;4wks. Progression free survival (PFS) was defined from the start of BLT-D until discontinuation or change in therapy due to progressive disease as clinically indicated. Toxicity was graded according to WHO criteria. Results :15 pts received BLT-D and their characteristics were as follows: all were males; median age 66 (range 30–78); IgG=53%, IgA=20%, light chain only=27%; Durie-Salmon stage I=20%, II=33%, III=47%; International Staging System stage I=20%, II=47%, III=13%, undefined = 20%; 7 were previously treated (5 pts had 1 prior regimen, 2 pts had ≥2 prior regimens). In previously treated pts (n=7) responses were as follows: no CR, 2 VGPR (28%), 3 PR (43%), 1 SD (14%) and 1 NR (14%) for an overall response rate (ORR) of 87%. Their duration of treatment ranged from 4–32 mos and median PFS in responders (VGPR+PR+SD) was 29.5 mos (range 23–35). 3 pts had BLT-D discontinued after 12–15 months of therapy and remained in stable plateau phase off therapy for &gt; 1 year; one was referred for ASCT after 14 mo; one continues stable at 15 mo and the third relapsed at 12 months but failed to respond again to BLT-D. Responses in treatment naive pts (n=8) were as follows: no CR, 3 VGPR (38%), 1 PR (13%) and 2 SD (25%), 2 NR (25%) for an ORR of 75%. Their duration of therapy ranged from 3–20 mos and median PFS in responding patients was 11 mos (range 7–20). The longest survivor in this group (37 mos) received an ASCT after 12 mos of therapy. 13 pts (87%) remain alive at a median follow-up of 24 mos (range 8–37). Grade 3–4 toxicity consisted of 3 DVTs + 1 PE (27%), 5 hypergycemias (33%), 2 infections (13%) and 1 peripheral neuropathy (7%). Additionally, 1 pt developed superficial thrombophlebitis; 1 QT prolongation resolving with Biaxin discontinuation; 5 others with neuropathy; and 2 others with hyperglycemia. Conclusion : BLT-D is feasible and effective therapy in African-American patients with MM and is capable of inducing durable responses. However, we encountered significant thrombotic and endocrine toxicity that appears out of proportion to what has been previously reported with thalidomide plus dexamethasone alone. Furthermore, aspirin thromboprophylaxis at daily doses of 81–325 mg appears suboptimal in preventing thromboembolic events in this group of patients when prescribed this regimen.

scholarly journals Dynamic Changes in International Staging System As a Predictor of Survival Outcome in Patients with Advanced Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4438-4438
Author(s):  
Jin-Liern Hong ◽  
Victoria Crossland ◽  
Aaron Galaznik ◽  
Paul Dolin
Keyword(s):  
Multiple Myeloma ◽  
Mortality Rate ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Study Cohort ◽  
Dynamic Changes ◽  
Beta 2 Microglobulin ◽  
Line Of Therapy

Abstract Background: The International Staging System (ISS) based on serum beta-2 microglobulin and serum albumin is a useful tool for risk stratification in patients with multiple myeloma. ISS is usually assessed at the time of diagnosis. Recent studies have suggested that risk stratification should be considered dynamic over the disease course. Our study aimed to describe dynamic changes in ISS over time and their impacts on mortality in patients with advanced multiple myeloma. Methods: This study included 417 patients with multiple myeloma from the Flatiron medical records database (Jan 2011- May 2018) who have received at least two lines of therapy and had data on ISS at the time of diagnosis (TDX) and at the time of initiating the second line of therapy (T2L). ISS stage was either abstracted from medical records or derived from the results of laboratory tests of serum beta-2 microglobulin and serum albumin. Patients were followed up from T2L until the earliest event of the last activity in database or death. We calculated mortality rates by TDX and T2L ISS stages, and generated Cox proportional hazard models to estimate the impact of TDX and T2L ISS stages on mortality. Additionally, in the subgroup of patients in ISS stage III at TDX, we used univariate logistic models to identify the predictors for downward shift to ISS stage I or II at T2L. Results: The study cohort had a median age of 70 (interquartile range: 61 to 77), and 59% were male. Based on ISS at TDX, 30%, 37%, and 33% of the study cohort were classified as stage I, II, and III with the mortality rate of 12, 11, and 24 deaths per 100 person-years, respectively. The hazard ratios were 0.95 (95% confidence interval (CI): 0.57-1.61) for patients in stage II and 1.96 (95% CI: 1.22-3.16) for patients in stage III, compared with patients in stage I. Based on ISS at T2L, 47%, 34%, and 20% were classified as stage I, II, and III, with the mortality rate of 7, 19, and 39 deaths per 100 person-years, respectively. The hazard ratios were 2.62 (95% CI: 1.61-4.25) for patients in stage II and 5.18 (95% CI: 3.10-8.64) for patients in stage III, compared with patients in stage I. Dynamic changes in ISS stages over time and mortality rates were depicted in the Table. Among patients in ISS stage I at TDX, about 25% shifted to higher stages at T2L, and had a higher mortality rate (26 per 100 person-years) than did patients remaining in stage I (8 per 100 person-years). For patients in ISS stage II at TDX, 43% stayed in Stage II at T2L, and 46% moved down to Stage I, with a mortality rate of 20 and 5 per 100 person-years, respectively. Among patients in ISS stage III at TDX, 58% moved down to lower stages at T2L. The mortality rate was 10, 21, and 40 per 100 person-years for patients moving down to Stage I and II at T2L and those remaining in Stage III, respectively. In the subgroup of patients in ISS stage III at TDX, strong predictors for shifting down to lower stages were younger age (odds ratio: 2.65; 95% CI:1.20-5.87 for age <65 vs ≥65 years) and serum creatinine ≤ 2 mg/dL at TDX (odds ratio: 2.26; 95% CI:1.03-4.92 for serum creatinine ≤ 2 vs >2 mg/dL), but not gender, race, or cytogenetic abnormality of del17p, t(4;14), and t(14;16). Conclusion: Large changes in ISS stages were observed in multiple myeloma patients when advancing the line of therapy. Changes in ISS stage were also associated with survival outcome. A downward shift to stage I was associated with substantially improved overall survival; in contrast, patients moving up to or remaining in higher stages had poor outcomes, especially for those remaining in ISS stage III. Our results suggest that re-evaluating ISS stage at the time of change in line of therapy can improve prediction of survival outcomes. Disclosures Hong: Takeda Pharmaceuticals International Co.: Employment. Crossland:Takeda Pharmaceuticals International Co.: Employment. Galaznik:Takeda Pharmaceuticals International Co.: Employment. Dolin:Shire: Other: PD holds shares in Shire ; GSK: Other: PD holds shares in GSK; Takeda Pharmaceuticals International Co.: Employment.

scholarly journals The expression of p53 protein in patients with multiple myeloma

2007 ◽  
Vol 135 (1-2) ◽  
pp. 43-47 ◽  
Author(s):  
Olivera Markovic ◽  
Dragomir Marisavljevic ◽  
Vesna Cemerikic ◽  
Maja Perunicic ◽  
Milica Colovic
Keyword(s):  
Multiple Myeloma ◽  
Clinical Significance ◽  
Median Survival ◽  
Plasma Cells ◽  
Histological Grade ◽  
Stage I ◽  
Newly Diagnosed ◽  
P53 Expression ◽  
P53 Immunoreactivity ◽  
Histological Stage

Introduction: Although mutations of p53 are one of the most often acquired genetic changes in malignant tumors, these mutations are rare events in patients with newly diagnosed multiple myeloma (MM). Moreover, there are a few literature data about clinical significance of p53 overexpression in multiple myeloma. Objective The aim of our study was to evaluate the clinical significance of p53 immunoexpression in multiple myeloma. Method A total of 58 patients with newly diagnosed MM (26 females and 32 males, mean age 62 years) were enrolled in the study. The diagnosis of MM was made according to criteria of Chronic Leukemia-Myeloma Task Force. Clinical staging was done according to Durie and Salmon classification (4 patients had disease stage I, 15 patients stage II and 39 patients stage III). The histological grade and histological stage were determined according to predominant plasma cell morphology and volume of myeloma infiltration, respectively. Standard immunohistochemical analysis with p53 antibody in B5-fixed and paraffin- embedded bone marrow specimens was used to evaluate the expression of p53 in myeloma cells. The specimens were considered positive when ?5% of plasma cells exhibited clear nuclear positivity. Results Out of 58 patients, p53 expression was detected in 9 (15.52%). No significant correlation was found between p53 expression and clinical stage (I+II vs. III), ?2-microglobulin level (?6 mg/L vs. >6mg/L), histological grade (I vs. II+III), histological stage (<20% vs. 21-50% vs. >50%) and the extent of osteolytic lesions (?3 vs. >3 lesions). Median survival of patients with p53 immunoreactivity in =>5% of plasma cells was 10 months, whilst median survival of patients with p53 immunoreactivity in <5% of plasma cells was 36 months. However, such difference was not significant (p=0.2). Conclusion The frequency of p53 immunoexpression in our group of newly diagnosed MM was relatively low. Although p53 immunoexpression was not associated with clinical and histological features of more aggressive disease, or with shorter survival, further investigations of larger group of patients will lead to final conclusions.

scholarly journals Circ-SMARCA5 suppresses progression of multiple myeloma by targeting miR-767-5p

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Haiyan Liu ◽  
Yan Wu ◽  
Shunye Wang ◽  
Jie Jiang ◽  
Chenlu Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cell Activity ◽  
Staging System ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Proliferation And Apoptosis ◽  
Underlying Mechanisms ◽  
Beta 2 Microglobulin

Abstract Background We aimed to investigate the correlation of Circ-SMARCA5 with disease severity and prognosis in multiple myeloma (MM), and its underlying mechanisms in regulating cell proliferation and apoptosis. Methods Bone marrow samples from 105 MM patients and 36 healthy controls were collected for Circ-SMARCA5 expression measurement. And the correlation of Circ-SMARCA5 expression with patients’ characteristics and survival was determined. In vitro, the effect of Circ-SMARCA5 on MM cell proliferation and apoptosis was evaluated by altering Circ-SMARCA5 expression through transfection. Rescue experiments and luciferase assay were further performed to explore the mechanism of Circ-SMARCA5 as well as its potential target miR-767-5p in regulating MM cell activity. Results Circ-AMARCA5 was downregulated in MM and presented a good value in distinguishing MM patients from controls and it was also negatively correlated with Beta-2-microglobulin (β2-MG) level and International Staging System (ISS) stage. Additionally, Circ-SMARCA5 high expression was associated with higher CR as well as better PFS and OS. As for in vitro experiments, Circ-SMARCA5 expression was lower in MM cell lines compared with normal cells, and Circ-SMARCA5 overexpression inhibited cell proliferation but promoted cell apoptosis in RPMI8226 cells. Rescue experiments disclosed that the effect of Circ-SMARCA5 on cell activity was attenuated by miR-767-5p, and luciferase reporter assay revealed direct binding between Circ-SMARCA5 and miR-767-5p. Conclusions Circ-SMARCA5 is downregulated and correlated with lower β2-MG level and ISS stage as well as better prognosis in MM patients, and it inhibits proliferation but promotes apoptosis of MM cells via directly sponging miR-767-5p.

scholarly journals Prognostic value of pretreatment serum beta 2 microglobulin in myeloma: a Southwest Oncology Group Study [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 823-830 ◽  
Author(s):  
BG Durie ◽  
D Stock-Novack ◽  
SE Salmon ◽  
P Finley ◽  
J Beckord ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Median Survival ◽  
Prognostic Significance ◽  
Phase Iii ◽  
Oncology Group ◽  
Southwest Oncology Group ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Pretreatment Serum

Six hundred twelve eligible, previously untreated patients with active multiple myeloma and at least some data available for analysis were entered into a randomized trial (Southwest Oncology Group [SWOG] Phase III myeloma study 8229/30), in which the prognostic significance of pretreatment serum beta 2 microglobulin levels was evaluated. Because there was no statistically significant survival difference between the alternating and syncopating VMCP/VBAP regimens, it was possible to evaluate serum beta 2 microglobulin for the total population all together. The serum beta 2 microglobulin measurements showed the highest significance of any prognostic factor, both in the bivariate and multivariate regression analyses. The median survival was 36 months for the 322 patients with pretreatment serum beta 2 microglobulin values of less than 6 micrograms/mL, as compared with a median survival of 23 months for the 225 patients with a beta 2 level of greater than or equal to 6 mcg/mL (P less than .0001). The stepwise multiple regression model first contained serum beta 2 microglobulin, followed by serum albumin, serum calcium, age, and serum creatinine. Serum beta 2 microglobulin was highly correlated with stage: median values ranged from 3.7 micrograms/mL for stage IA, to 10.1 for stage IIIB. It was possible to stratify myeloma patients based on combinations of serum beta 2 microglobulin with both albumin and age, producing excellent separation of patients into low-, intermediate-, and high-risk categories. It is concluded that serum beta 2 microglobulin is the most powerful prognostic factor currently available for multiple myeloma and that it can be used alone or in combination with other variables for pretreatment stratification.

scholarly journals The Clinical Features of Multiple Myeloma with AL Amyloidosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Junichiro Nashimoto ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Kota Sato ◽  
Kanji Miyazaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Light Chain ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Staging System ◽  
Stage I ◽  
P Value ◽  
Al Amyloidosis ◽  
Hepatic Amyloidosis

Background Multiple myeloma and AL amyloidosis are both caused by the clonal proliferation of the abnormal plasma cells. Although, the difference of the genetic features of multiple myeloma and AL amyloidosis has been reported, we see some patients present with both cases. We retrospectively investigated the clinical features of patients diagnosed with multiple myeloma and AL amyloidosis. Methods We reviewed medical records of patients who were diagnosed with multiple myeloma and AL amyloidosis before initiating treatment during January 2009 to November 2019 in our institution. We excluded patients who did not reach 10% of the plasma cells in the bone marrow. Patients diagnosed with light chain deposition disease were excluded. Treatment regimens were at the discretion of the treating physician. Results Forty-two patients were diagnosed with multiple myeloma and AL amyloidosis. The median follow-up time since diagnosis was 20 months [0-89]. The median age was 63-year-old [43-85]. There was no difference between the sex (male: female=1:1). Twenty-nine (69.0%) patients had lambda type of light chain. Patients with ISS stage I, II, and III were 13(31.7%), 21(51.2%), and 7(17.1%). Patients with R-ISS stage I, II, and III were 4(10.3%), 30(76.9%), and 5(12.8%). Patients with Revised Mayo Clinic AL amyloidosis Staging System 1, 2, 3, and 4 were 3(10.0%), 4(13.3%), 8(26.7%), and 15(50.0%). Twelve (35.3%), 2 (6.9%), 1 (3.4%) and 1 (4.0%) patients had t(11;14), t(4;14), t(14;16) and del(17p) by FISH analysis, respectively. Fourteen (33.3%), 16(38.1%), and 8(19.0%) patients were diagnosed with cardiac, renal, and hepatic amyloidosis, respectively. Thirty-five (83.3%) patients received Bortezomib containing regimen for the initial treatment (e.g., Bortezomib+Dexamethasone(7.1%), Cyclophosphamide+Bortezomib+Dexamethasone(23.8%), Bortezomib+Melphalan+Dexamethasone(7.1%), Bortezomib+Melphalan+Prednisolone(9.5%), Bortezomib+Lenalidomide+Dexamethasone(35.7%)). Thirteen (31.0%) patients underwent autologous stem cell transplantation with high dose melphalan. Median PFS was 25 months and the median OS was 82 months. There were no significant differences in OS between the I-SSS, R-ISSS, and Revised Mayo Clinic AL amyloidosis Staging System groups. Patients diagnosed with cardiac or hepatic amyloidosis had significantly worse outcome. The median OS diagnosed with and without cardiac amyloidosis were 14 and 28 months (p value = 0.034), and the median OS diagnosed with and without hepatic amyloidosis were 8 and 24 months (p value = 0.012). Conclusion Multiple myeloma with AL amyloidosis, especially cardiac or hepatic amyloidosis, has a poor prognosis even if treated with novel agents. Searching for the optimal treatment for these patient groups remains to be an issue. Disclosures Nashimoto: Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Ishida:Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Speakers Bureau. Suzuki:Bristol-Myers Squibb, Celgene and Amgen: Research Funding; Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria.

Validation of International Staging System (ISS) for Multiple Myeloma: A Retrospective Analysis of 487 Patients at 8 Brazilian Centers.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5069-5069
Author(s):  
Vania T.M. Hungria ◽  
Angelo Maiolino ◽  
Gracia Martinez ◽  
Gisele Colleoni ◽  
Luciana Oliveira ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Median Survival ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
High Dose ◽  
International Staging System ◽  
New System

Abstract Introduction: The survival of patients with multiple myeloma varies from a few months to more than 10 years. This heterogeneity is related to the characteristics of the myeloma itself and of the host. The identification of the factors which influence the prognosis is very important to predict the result, assist in the choice of the treatment and adequately stratify the patients in clinical studies. Many prognostic factors have been identified in patients with multiple myeloma, such as anemia, renal failure, ß2 microglobulin, albumin and chromossomic alterations. Some authors have combined prognostic factors and proposed various systems of staging. However, none of them have yet substituted the Durie-Salmon staging system. Recently, the International Myeloma Working Group, with the objective of developing a simple and reliable staging system, which can be internationally applied to classify and stratify patients with multiple myeloma, identified 3 risk groups. This new system of staging, the “International Staging System” (ISS), consists of stage I: ß2 microglobulin &lt; 3.5 mg/L plus albumin ≥ 3.5 g/dL (median survival: 62 months); stage II: neither I nor III (median 44 months); stage III: ß2 microglobulin &gt; 5.5 mg/L (median 29 months). This study included sites in North America, Europe and Asia, but the sites in Latin America were not included. Objective: To validate the ISS in patients with multiple myeloma at Brazilian centers. Patients and Methods: Four hundred and eighty-seven patients with the diagnosis of multiple myeloma within the period of 1998 to 2004 at Santa Casa de São Paulo, Hospital Universitário Clementino Fraga Filho do Rio de Janeiro, Hospital das Clínicas de São Paulo, Hospital São Paulo, Hospital das Clínicas de Ribeirão Preto, HEMOPE, Hospital Prof. Edgar Santos de Salvador and Hospital de Clínicas de Porto Alegre, with available data on albumin and ß2 microglobulin, were stratified according to the ISS. A total of 339 patients received standard therapy and 148 received high-dose therapy as initial therapy. The survival was estimated using the Kaplan-Meier method with differences in survival examined using the logrank test. Results: The median age of the patients was 60 years, 52% male and 48% female. In Stage I (n=104), the global median survival was not reached, the survival at 60 months was 60%, in stage II (n=264), the global median survival was 61 months and in stage III (n=119), 19 months (p&lt;0.001). Conclusion: The new system of staging for multiple myeloma (ISS) is simple, based on variables easy to be applied and was possible to be validated in patients with multiple myeloma in Brazilian centers.

Comorbid Diabetes Does Not Impact the Survival of Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5003-5003
Author(s):  
Liang-Tsai Hsiao ◽  
Tzeon-Jye Chiou ◽  
Ying-Chung Hong ◽  
Chun-Yu Liu ◽  
Yuan-Bin Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Laboratory Tests ◽  
Elevated Serum ◽  
Stage I ◽  
Stage Iii ◽  
Treatment Modalities ◽  
High Dose ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Abstract Abstract 5003 Background & aims. For patients with multiple myeloma (MM), comorbid type II diabetes mellitus (DM) has leaded additional consideration and complications. Preceding DM in MM patients may have lead to end-organ damage involving cardiovascular, renal and nervous systems, and the use of glucocorticoids - the mainstay of anti-myeloma agents - further impairs glycemic control. However, it is not well studied at present whether comorbid DM itself will influence clinical features and prognosis of MM patients. Methods. Patients who were newly diagnosed in Taipei Veterans General Hospital between 1996 and 2007 were enrolled. Data of clinical features, comorbidities, and laboratory tests at diagnosis, treatment modalities, and survival at last follow up were collected. MM patients with or without DM was compared in terms of clinical/laboratory tests and outcome. Results. There were 389 MM patients (M/F=288/101, 74% vs. 26%) with median age of 71 years, with the features summarized in the Table. The immunophenotypes consisted of IgG (194, 49.9%), IgA (113, 29%), and light chain diseases (LCD) (67, 17.2%). Clinical stages included Durie-Salmon (DS) stage I/II/III = 7.2%/20.1%/72.7% and International Staging System (ISS) stage I/II/III = 14.5%/29.3%/56.2%. Serum Cr > 2.0 mg/dL at diagnosis was noted in 34%. Sixty patients (15.4% of 389) had DM preceding the diagnosis of MM. There was no statistical difference of median age, gender distribution, DS stages, and renal impairment when comparing MM patients with or without comorbid DM.MM patients with comorbid DM were associated with a lower prevalence of IgA-type diseases (with vs. without DM= 17% vs. 32%, P=0.094), an elevated serum beta-2 microglobulin >5 mg/L (with vs. without DM = 75% vs. 52%, P=.006), and ISS-stage III disease (with vs. without DM = 75% vs. 53%, P=.005). In terms of anti-myeloma therapy, the proportion of MM patients with or without DM who once received thalidomide, bortezomib and high-dose chemotherapy plus stem cell transplantation (HDT and SCT), and bisphosphonates were similar. The median overall survival (OS) of all patients was 20.5 months. The OS was well correlated with ISS stages (I vs. II vs. III = 51.2 vs. 27.2 vs. 13.4 months, P<0.001) but was not with comorbid DM. Conclusions. Comorbid DM was present in up to 15% of MM patients, and was more frequently associated with elevated serum beta-2 microglobulin (>5 mg/L) and ISS-stage III diseases; however, comorbid DM did not significantly influence the OS. Therefore, comorbid DM itself should not be considered as a contraindication of aggressive anti-myeloma treatments at present. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic value of pretreatment serum beta 2 microglobulin in myeloma: a Southwest Oncology Group Study [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 823-830 ◽  
Author(s):  
BG Durie ◽  
D Stock-Novack ◽  
SE Salmon ◽  
P Finley ◽  
J Beckord ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Median Survival ◽  
Prognostic Significance ◽  
Phase Iii ◽  
Oncology Group ◽  
Southwest Oncology Group ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Pretreatment Serum

Abstract Six hundred twelve eligible, previously untreated patients with active multiple myeloma and at least some data available for analysis were entered into a randomized trial (Southwest Oncology Group [SWOG] Phase III myeloma study 8229/30), in which the prognostic significance of pretreatment serum beta 2 microglobulin levels was evaluated. Because there was no statistically significant survival difference between the alternating and syncopating VMCP/VBAP regimens, it was possible to evaluate serum beta 2 microglobulin for the total population all together. The serum beta 2 microglobulin measurements showed the highest significance of any prognostic factor, both in the bivariate and multivariate regression analyses. The median survival was 36 months for the 322 patients with pretreatment serum beta 2 microglobulin values of less than 6 micrograms/mL, as compared with a median survival of 23 months for the 225 patients with a beta 2 level of greater than or equal to 6 mcg/mL (P less than .0001). The stepwise multiple regression model first contained serum beta 2 microglobulin, followed by serum albumin, serum calcium, age, and serum creatinine. Serum beta 2 microglobulin was highly correlated with stage: median values ranged from 3.7 micrograms/mL for stage IA, to 10.1 for stage IIIB. It was possible to stratify myeloma patients based on combinations of serum beta 2 microglobulin with both albumin and age, producing excellent separation of patients into low-, intermediate-, and high-risk categories. It is concluded that serum beta 2 microglobulin is the most powerful prognostic factor currently available for multiple myeloma and that it can be used alone or in combination with other variables for pretreatment stratification.

Sign in / Sign up

Export Citation Format

Share Document