scholarly journals The Role of18F-FDG PET/CT in Multiple Myeloma Staging according to IMPeTUs: Comparison of the Durie–Salmon Plus and Other Staging Systems

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Shengming Deng ◽  
Bin Zhang ◽  
Yeye Zhou ◽  
Xin Xu ◽  
Jihui Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factors ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Deauville Score ◽  
Staging Systems

We aimed at comparing the Durie–Salmon Plus (DS Plus) staging system based on Italian Myeloma criteria for PET USe (IMPeTUs) with other two staging systems in predicting prognosis of patients with all stages of newly diagnosed multiple myeloma (MM). A total of 33 MM patients were enrolled in this retrospective study. The variation between the DS Plus classification and Durie–Salmon staging system (DSS) or Revised International Staging System (RISS) classification was assessed. When staged by the DSS, patients in stage I and stage II did not reach the median overall survival (OS), and the median OS was 33 months for stage III (p=0.3621). When staged by the DS Plus, patients in stage I did not reach the median OS of stage I, and the median OS for stages II and III was 38 and nine months, respectively (p=0.0064). When staged by the RISS, patients in stage I did not reach the median OS, and the median OS was 33 and 16 months for stage II and stage III, respectively (p=0.0319). The concordances between two staging systems were 0.07 (DS Plus versus DSS) and 0.37 (DS Plus versus RISS), respectively. Multivariate analysis revealed that DS Plus stage III (HR: 11.539,p=0.021) and the Deauville score of bone marrow ≥4 (HR: 3.487,p=0.031) were independent prognostic factors associated with OS. Both the DS Plus based on IMPeTUs and RISS possessed a better potential in characterizing and stratifying MM patients compared with the DSS. Moreover, DS Plus stage III and the Deauville score of bone marrow ≥4 were reliable prognostic factors in newly diagnosed MM patients.

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 < 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 > 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<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.

The Role of Cytokines, Growth and Angiogenic Factors in Patients with NEWLY Diagnosed Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4997-4997
Author(s):  
Gurhan Kadikoylu ◽  
Hakan Dogan ◽  
Mukadder Serter ◽  
Aslihan Karul ◽  
Ibrahim Meteoglu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Growth Factor ◽  
Staging System ◽  
Angiogenic Factors ◽  
Stage I ◽  
Stage Iii ◽  
Control Group ◽  
Newly Diagnosed

Abstract Abstract 4997 The cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-a may play some roles in both the pathogenesis of multiple myeloma (MM) and bone destruction. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and angiopoietin (Ang)-2 in recent years may trigger angiogenesis in MM. Moreover transforming growth factor (TGF)-β and insulin-like growth factor (IGF)-1 induce angiogenesis and proliferation of myeloma cells. In this prospective study, we investigated the role of cytokines, growth and angiogenic factors in patients with newly diagnosed MM. Fifty patients (32 were male and 18 female, with mean age of 63 ± 11 years) with newly diagnosed MM were enrolled to this study. Local ethical commity of our university approved this study. 30 healthy individuals (12 were male and 8 female, with mean age of 55±9 years) were selected as control group. The exclusion criteria were malignancy, acute and chronic infections, autoimmune disorders, diabetes mellitus, immune deficiency, and chronic inflammatory diseases. According to Durie-Salmon staging system, 10%, 22%, and 68% of the patients with MM were in Stage I, Stage II and Stage III, respectively. 17%, 44%, and 39% of patients with MM were in International prognostic index-1 (IPI1), IPI2, and IPI3, respectively. 90% of the patients were symptomatic MM, 6% of them were smoldering MM, and solitary plasmacytoma was detected in 4% of the patients. The levels of IL-1β, IL-2, IL-6, IL15, TNF-a, VEGF, bFGF, TGF-β, HGF, IGF-1, Ang-1 and Ang-2 were determined using ELISA in patients and controls. VEGF and nuclear factor kappa-B (NFkB) were evaluated as immunohistochemistry in bone marrow biopsy in patients and pathological control group (13 were male and 6 female, with mean age of 64±14 years) with non-Hodgkin's lymphoma and without bone marrow involvement. In this study, the levels of IL-1β (p<0. 001), IL-2 (p<0. 001), IL-6 (p<0. 001), TNF-a (p<0. 001), IGF-1 (p<0. 001), TGF-β (p<0. 001), HGF (p=0. 004), and Ang-2 (p<0. 001) in patients were higher than controls. But there was no difference for Ang-1, IL-15, and VEGF in between two groups (p>0. 05). According to immunohistochemistry scoring, while NFkB scores in patients were higher than controls (p=0. 035), any significance was not detected for VEGF in between patient and pathological control groups (p>0. 05). According to Durie-Salmon staging system, TNF-a levels in Stage I were higher than Stage III (p=0. 035). According to IPI, TGF-β levels in patients with IPI-1 were higher than the patients with IPI-2 (p=0. 017) and IPI-3 (p=0. 003). The pathogenesis of MM is stil unclear. In this study, although VEGF did not increase, increment in the levels of Ang-2 and other growth factors indicated the induction of angiogenesis in MM. In earlier stage, this condition may be apparent. Disclosures: No relevant conflicts of interest to declare.

Personalized Treatment with low doses of Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma in frail or Elderly Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5049-5049
Author(s):  
Angel Ruedas ◽  
Pablo Guisado ◽  
Beatriz Aguado ◽  
Ricardo Perez ◽  
Joaquin Martinez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Elderly Patients ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Light Chains ◽  
Bone Marrow Toxicity ◽  
Low Doses ◽  
Very Elderly

Abstract Abstract 5049 Background. Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims. To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods. The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results. 38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions. Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures: No relevant conflicts of interest to declare.

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.

Tailored Low Dose Lenalidomide with Low Dose Dexamethasone (len/dex) in Previously Treated Patients with Multiple Myeloma Older Than 70 Years Requiring Treatment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4950-4950
Author(s):  
Angel Ruedas ◽  
Ricardo Perez ◽  
Valentin Garcia ◽  
Alicia Smucler ◽  
Pilar Bravo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Elderly Patients ◽  
Low Dose ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Bone Marrow Toxicity ◽  
Low Doses ◽  
Previously Treated

Abstract Abstract 4950 Background & Aims The management of elderly patients with Multiple Myeloma (MM) previously treated requiring further therapy (although in most cases palliative) is very difficult due to the presence of concomitant diseases, decreased bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. As in this setting the tolerability of standard doses of conventional chemotherapy, high doses of dexamethasone or IMiDs is a concern, we report the preliminary results of the combination of tailored low doses of lenalidomide (len) and low doses of dexamethasone (dex). Methods We retrospective analyze the results of the combination of low dose lenalidomide and low dose of dexamethasone (len/dex) in 14 patients aged over 70 years with pretreated MM and progressive disease. Low doses of len (5-10 mg daily for 21days) were initially given and flexibly modified in subsequent cycles according to response and toxicity, along with low doses of dex (20-40 mg/day for 4 days) in most (12) patients. G-CSF and red cell transfusions were used when needed. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. Results Median age was 80 years (70-90). All patients had received between 2-5 different previous modality treatments (m=2), including bortezomib (7), thalidomide (4) or PBSCT (2). 11 pts had IgG, m=3397mg/dl (868-4990), 2 IgA m=1460 (1050-1870) and another one BJ. 9 pts had κ and 4 » light chains. Median Hemoglobin level was 10 gr/dl (7.2-11.4) and median creatinine level 1.19 mg/dl (0.75-1.63). 11 (78%) had bone disease. 9 pts had S&D stage II, 4 stage III and another one stage I. 7 pts had ISS stage II, 4 had stage I and 2 stage III. Patients received between 2 and 13 cycles of len/dex (m=6.8). 11 pts (78%) achieved Partial Remission (PR) and 2 (14%) achieved significant, but lesser that 50%, reduction of the M-component (Stable Disease: Std). Overall response (PR+Std) occurred in 13/14 patients (92.8%). The best response occurred between 2-12 cycles of len/dex. Grade III-IV bone marrow toxicity occurred in 5 pts (35 %) and neurological toxicity (PNP) in 5 pts (35%) (all of them had received previous bortezomib or thalidomide). Treatment was stopped in 6 pts: for unrelated causes (1), due to neurological (3) or haematological (1) toxicity and in 2 pts after achieving Std and both relapsed after 3 months. Conclusions Treatment with tailored low doses of lenalidomide and low doses of dexamethasone (len/dex) is an active and tolerable option for previously treated elderly patients with symptomatic MM. Low lenalidomide doses can be flexibly modified according to the quality of the response and the hematological toxicity that is expectable and manageable. Previous treatments with bortezomib or thalidomide is associated with neurotoxicity. Disclosures No relevant conflicts of interest to declare.

scholarly journals Masaoka-Koga and TNM Staging System in Thymic Epithelial Tumors: Prognostic Comparison and the Role of the Number of Involved Structures

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5254
Author(s):  
Marco Chiappetta ◽  
Filippo Lococo ◽  
Luca Pogliani ◽  
Isabella Sperduti ◽  
Diomira Tabacco ◽  
...  
Keyword(s):  
Staging System ◽  
Tnm Staging ◽  
Multiple Organ ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
Tnm Staging System ◽  
Staging Systems

Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka–Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. Results: Considering the Masaoka–Koga system, 5- and 10-year overall survival (5–10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5–10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2–T3 curves. Including the number of involved structures, in Masaoka–Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5–10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5–10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka–Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

Prognostic Value of Bone Marrow Angiogenesis in Newly Diagnosed Multiple Myeloma: A Comparison with Conventional Prognostic Factors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5111-5111
Author(s):  
Shaji Kumar ◽  
Jessica L. Haug ◽  
Linda Wellik ◽  
Thomas E. Witzig ◽  
John A. Lust ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Prognostic Value ◽  
Staging System ◽  
Continuous Variable ◽  
Newly Diagnosed ◽  
Grade Group

Abstract Background: Abnormally increased tumor associated neovasculature plays an important role in tumor progression in solid tumors and hematological malignancies. In multiple myeloma (MM) bone marrow angiogenesis, measured in terms of microvessel density (MVD), has prognostic value, and appear to increase with disease progression from monoclonal gammopathy of undetermined significance to relapsed MM. We have shown that MVD has prognostic value in patients with newly diagnosed MM including patients undergoing upfront high dose therapy and stem cell transplantation, but comparison with other known prognostic factors has been limited by sample size. It is also not known whether the MVD adds prognostic value once the recently described International Staging System (ISS) is applied. The goal of this study was to determine the prognostic effect of bone marrow MVD in newly diagnosed MM relative to the ISS and other known prognostic factors. Methods: We studied 400 patients with newly diagnosed MM seen at the Mayo Clinic between March of 1988 and December 2001. Sections from bone marrow biopsy blocks from the time of initial diagnosis were studied by immunohistochemistry using antibodies against CD34 antigen to high light the endothelial cells. Under low power (100X); three areas with maximum number of microvessels (hotspots) were identified. Each of these areas was further studied at 400X magnification and the number of microvessels per high power field counted. The average of the three readings was taken as the MVD for the sample. In addition, the samples were graded as low, intermediate or high by using a visual estimate as previously described. Additional clinical data was extracted from medical records. Some of the patients have been included in previous studies related to angiogenesis. Results: A total of 400 patients in whom a bone marrow biopsy from within 30 days of diagnosis was available were studied. The pts were followed for a median of 37 months (Range: 1 month to 16.5 years) and 318 pts (80%) had died at the time of this analysis. The median MVD for the entire group was 14.7 (Range 0–168). The median overall survival for the three groups according to the MVD grade was lower for the high grade group (31.9 months) compared to the intermediate grade group (37.2 months) and the low grade group (not reached); P &lt;0.029, log rank test. We examined this group of patients for other factors prognostic for overall survival. Factors significant on univariate analysis included ISS stage, platelet count (&lt;150 vs. &gt;= 150 X 106/L), and plasma cell labeling index (&lt;1 vs &gt;=1). In a multivariate analysis using these variables and MVD as a continuous variable, high MVD and the ISS staging system were significantly associated with poorer survival (Table). Conclusion: In this large group of pts with newly diagnosed MM, we confirm the prognostic value of increased bone marrow angiogenesis. We examined the MVD as a continuous variable in the multivariate analysis for a closer evaluation of this measure in this comparison. More importantly, the prognostic value appears to be independent of the ISS and other major prognostic factors. The resultsof this study reinforces the biological relevance of this finding in MM. HR 95% CI P value MVD 1.006 (1.001, 1.011) 0.0279 ISS Stage I 0.37 (0.25, 0.56) &lt;0.001 ISS Stage II 0.58 (0.41, 0.83) 0.0025

scholarly journals The Association of International Staging System (ISS) Stage with Disease and Symptom Burden in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2115-2115
Author(s):  
Mark A Fiala ◽  
Michael Slade ◽  
Jesse Keller ◽  
Keith Stockerl-Goldstein ◽  
Michael Tomasson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Performance Status ◽  
Symptom Burden ◽  
Staging System ◽  
Stage I ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Bone Marrow Plasma ◽  
International Staging System

Abstract Background: The clinical presentation of multiple myeloma (MM) varies greatly but often includes bone pain, anemia, renal dysfunction, hypercalcaemia, and/or constitutional symptoms. There are no signs or symptoms that are disease specific. The earliest staging system for MM, the Durie-Salmon (DS), associated disease and symptom burden with prognosis; however, it has been largely replaced by the International Staging System (ISS), which is easier to compute and better identifies patients with the poorest prognosis. It is unclear if ISS stage, like DS, is associated with disease or symptom burden. Objective: To compare disease and symptom burden of patients with newly diagnosed MM by ISS Stage. Methods: Data was extracted from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway corresponding with interim analysis 6 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data and patient reported quality of life (EORTC QLQ-C30 and QLQ-MY20), as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator and/or a proteasome inhibitor for initial MM treatment; and no prior malignancies in the past 5 years. All clinical data was reported by trained data analysts at the enrolling center with the exception of flow cytometry which was performed centrally; raw lab values for beta-2 microglobulin and albumin were entered and stage was subsequently calculated by the analysts for this study according to the ISS (Greipp et al, JCO 2005). Twenty-six patients with unknown ISS were excluded from the analysis. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with one-way ANOVA tests. Results: 599 patients were eligible for analysis. Sex, race, and heavy and light chain isotypes were all evenly distributed among the ISS stages; however, median age for ISS stage III was 67, 65 for stage II and 62 for stage I (p<0.001). Stage I and II patients were similar in disease burden, but stage III patients had higher serum M-proteins (p<0.001), LDH (p=0.002), bone marrow plasma cells (p<0.001), circulating plasma cells (p<0.001), and creatinine (p<0.001), and lower hemoglobin (p<0.001) and platelets (p=0.001). Further, stage III patients had poorer performance status (p<0.001), global health (p<0.001), physical functioning (p<0.001), social functioning (p<0.001), and role functioning (p<0.001), and increased fatigue (p<0.001) and pain (p=0.016). Results are summarized in Table 1. Conclusions: Stage III had a higher disease and symptom burden than stage I and II patients. Stage I and II patients were similar in most measures suggesting that ISS may not discriminate between these groups well, this is supported by other studies that have failed to find outcomes differences between stage I and II patients. Table 1. Stage I n= 204 Stage II n = 210 Stage IIIn = 185 p Demographics Age in years 62 65 67 <0.001 Male 64% 57% 62% NS Race NS White 80% 83% 74% Black 19% 13% 23% Other 2% 3% 3% Heavy Chain NS IgG 80% 80% 75% IgA 20% 20% 25% Light Chain NS Kappa 65% 61% 60% Lambda 34% 38% 38% Biclonal 1% 2% 2% Disease Burden Serum M-Protein g/dL 1.9 2.0 3.2 <0.001 LDH μkat/L 2.7 2.8 3.0 0.002 Bone Marrow Plasma Cells* 7% 9% 13% <0.001 Circulating Plasma Cells* 0% 0% 0.1% <0.001 Calcium mmol/L 2.4 2.3 2.4 <0.001 Creatinine μmol/L 82 88 149 <0.001 Hgb mmol/L 7.4 6.4 5.8 <0.001 Platelets x109/L 222 212 199 .001 Bone Lesions 61% 52% 53% NS Symptom Burden/Quality of Life Measures ECOG Performance Status <0.001 0 47% 42% 22% 1 49% 42% 54% 2 5% 8% 15% 3-4 0% 8% 9% Global Health Scale 66 66 50 <0.001 Physical Functioning Scale 86 80 63 <0.001 Cognitive Functioning Scale 83 83 83 NS Emotional Functioning Scale 75 75 75 NS Social Functioning Scale 83 83 66 <0.001 Role Functioning Scale 66 66 50 <0.001 Disease Symptom Scale 27 22 27 NS Fatigue Scale 33 33 44 <0.001 Pain Scale 33 33 42 0.016 Note-Median presented unless specified. *- CD38+/CD138+ by flow cytometry Disclosures Vij: Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy.

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P&lt;0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P&lt;0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

Clinical Staging for Sleep-Disordered Breathing

2002 ◽  
Vol 127 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Michael Friedman ◽  
Hani Ibrahim ◽  
Lee Bass
Keyword(s):  
Body Mass Index ◽  
Success Rate ◽  
Body Mass ◽  
Sleep Disordered Breathing ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Staging ◽  
Disordered Breathing

OBJECTIVE: The purpose of this study was to identify prognostic indicators that would lead to stratification of patients likely to have successful surgery for sleep-disordered breathing (SDB) versus those destined to fail. STUDY DESIGN: We retrospectively reviewed 134 patients to correlate palate position and tonsil size to the success of the UPPP as based on postoperative polysomnography results. Similar to our previously published data on the Friedman Score as a predictor of the presence and severity of SDB, the palate position was determined on physical examination of the oral cavity and was graded for each patient. This grade combined with tonsil size was used to stage the patients. Stage I was defined as having palate position 1 or 2 combined with tonsil size 3 or 4. Stage II was defined as having palate position 3 or 4 and tonsil size 3 or 4. Stage III patients had palate position 3 or 4 and tonsil size 0, 1, or 2. Any patient with body mass index of greater than 40 was placed in the stage III group. The results of uvulopalatopharyngoplasty (UPPP) were then graded as success or failure and success rates were compared by stage. SETTING: Academically affiliated tertiary care referral center. RESULTS: Stage I patients who underwent UPPP had a success rate of 80.6%, stage II patients had a success rate of 37.9%, and stage III patients had a success rate of 8.1%. CONCLUSION: A clinical staging system for SDB based on palate position, tonsil size, and body mass index is presented. It appears to be a valuable predictor of the success of UPPP. Additional studies and wider use of the staging system will ultimately define its role in the treatment of SDB.

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