Serum Kappa/Lambda Ratio, An Independent Prognostic Factor at Diagnosis and Serum Free-Light Chains Level, An Early Indicator of Relapse/Progression In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2954-2954
Author(s):  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Taoufik Guilli ◽  
Sophie Ducastelle-Lepretre ◽  
Fiorenza Barraco ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Conflicts Of Interest ◽  
Fish Analysis ◽  
Cox Regression Analysis ◽  
Serum Free ◽  
Treatment Type ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2954 Background: The serum free light chain (sFLC) analysis has been used for the diagnosis and monitoring of plasma cell dyscrasias and has proved its usefulness in disease treatment response in multiple myeloma (MM). Some studies have evaluated the prognostic value of the sFLC levels expressed as K/L ratio (sFLCR) at diagnosis. In contrast, performing this analysis during patient's follow up and on therapy is still not very well defined yet. Aim: Our first objective was to evaluate the impact of sFLCR, measured at diagnosis in MM patients, on the progression free survival (PFS) and overall survival (OS); the second objective was to assess the importance of sFLC analysis during the follow-up especially for relapse/progression detection comparing to concomitant monoclonal-protein (M-p) traditional serum protein electrophoresis (sPE). Methods: Between years 2002 and 2008, we have analysed 174 MM patients for which a concomitant measurement of sFLC and sPE was done during follow-up. Only 118 patients had the sFLCR analysis performed at diagnosis. The sFLC analysis was performed using the Freelite™ test from the Binding site on a BNIIÒ, Dade BehringÓ, and for sPE, analysis was done using a Paragon CZE 2000Ò, Beckman CoulterÓ. There were 92 (53%) males and 82 (47%) females, median age at diagnosis 57 years (34-72), 120 (69%) were IgG (87K&33L), 52 (30%) IgA (41K&11L) and 2 (1%) IgD (1K&1L). According to the ISS, there were 16 (9%) in stage I, 17 (10%) in stage II and 141 (81%) in stage III. Among 61 (35%) FISH analysis done, 31 (51%) detected a chromosome 13 deletion. Twenty six (15%) patients had renal insufficiency. According to the distribution of the different ratios at diagnosis, we have defined three groups: group1 (n=25): patients with 0.13<sFLCR<3.3 which represents the double of the normal range (0.26-1.65); group2 (n=63): patients with sFLCR>3.3 and group3 (n=30): patients with sFLCR<0.13.We also monitored the behaviour of sFLC and sPE in a way to early detect relapse/progression independently of treatment type. Kaplan Meier and cox regression analysis were performed to study the PFS and OS in different groups, slopes of the increase period corresponding to each measurement were compared using the student t-bilateral test with R statistical software. Results: After a median follow-up of 38 months [3.3-93.7], the 5-years OS for groups 1, 2 and 3 was 75% [56-100], 60% [47-76] and 40% [23-69] respectively; and the 5-years PFS was 69% [49-96], 43% [31-60] and 29% [15-54] respectively. The multivariate analysis studying age, ISS, sex, cytogenetics and sFLCR, showed that both OS and PFS are worslty affected with a more abnormal sFLCR, hazard ratios (HR) in Figure1. After monitoring all patients, we observed 117 (67%) patients with relapse/progression and 57 (33%) patients were still in response to treatment. In 77 (66%) cases, relapse or progression was detected by concomitant increase of both sFLC and the M-p with a significant earlier increase for sFLC (Figure2A). In 17 (15%) patients, the relapse or progression was characterised by the only increase of sFLC without any increase of the M-p (Figure2B). Contrarily, in 5 (4%) patients there was only an increase of the M-p without increasing the sFLC (Figure2D). Finally, in 18 (15%) patients, the relapse or progression was revealed by the increase of M-p faster than the concerned sFLC (Figure2C). When comparing slopes of increasing sFLC to increasing M-p, we found a very high significant difference (p<0.001), thus showing that sFLC have a faster detection of relapse or progression. Conclusion: Our study has showed that abnormal sFLCR at diagnosis affects OS and more strongly the PFS independently of any other concomitant variable. In 81% of patients, sFLC analysis enabled an earlier detection of relapse/progression compared to sPE, this could be very important for early treatment intervention especially for high risk patients. Since there are no uniform recommendations for the use of this analysis during follow-up, we recommend its concomitant use with sPE, waiting for guidelines and we suggest that the sFLCR at diagnosis deserves more focus for its validation as a prognostic factor in MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunophenotypic Response After Allografting In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3371-3371 ◽  
Author(s):  
Luisa Giaccone ◽  
Lucia Brunello ◽  
Roberto Passera ◽  
Moreno Festuccia ◽  
Milena Gilestro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
First Line ◽  
Significant Difference ◽  
The Impact

Abstract Background Minimal residual disease (MRD) by multiparameter flow-cytometry recently showed a promising role in predicting outcomes in patients with multiple myeloma. However, data on immunophenotypic response (IR) after allografting are lacking. Aim To evaluate the impact of IR and compare it to conventional complete remission (CR) following allografting in myeloma patients. Methods Sixty-six consecutive patients, median age 54 years (35-66), who underwent an allograft between January 2000 and December 2011 with a follow-up of at least 3 months were included. Disease response was evaluated by serum and urine electrophoresis, and bone marrow aspirate at baseline, 3, 6, 12, 18, 24 months after transplant and yearly thereafter. Skeletal survey or MRI were performed yearly or as clinically indicated (overt relapse or complaints of bone pain). Bone marrow aspirates had to contain at least 13000 cells/µL for flow-cytometry studies and IR was defined as absence of monoclonal plasma-cells detected by 4 or 6-colour staining with the following antibodies: CD38, CD138, CD56, CD19, CD45, cyKappa, cyLambda. CR was defined according to standard criteria (Durie et al, Leukemia 2006; 20:1467-73). Results Conditioning regimen was non-myeloablative 2Gy TBI-based in 55 patients, reduced intensity (fludarabine-melphalan-based) in 10 and myeloablative in 1 patient. Post-grafting immunosuppression consisted of cyclosporine with mycophenolate mofetil or methotrexate. Donors were HLA identical siblings in 58 patients and unrelated in 8. Only 1 patient received bone marrow as source of stem cells. Thirty-five/66 (53%) received the allograft as part of the first line treatment, whereas the remaining 31/66, (47%) were transplanted at relapse. At the time of transplant, 5/66 were both in IR and CR, 16 were only in IR and 4 patients were only in clinical CR. All 21 patients in IR at the time of transplant maintained it, while 26/45 (58%) entered IR after the allograft. Among patients surviving at least 3 months, overall treatment related mortality was 10.6% at 3 years. After a median follow-up of 69 months (range 19-147), the incidence of acute and chronic graft-versus-host disease was 45.6% and 49.3% without significant difference between responsive and non-responsive patients. At follow-up, overall, 24 patients achieved CR and IR (CR/IR group), 21 achieved IR but not CR because of persistence of urine/serum M-component (noCR/IR group), and 21 did not achieve either CR or IR (noCR/noIR group). Interestingly, none achieved CR without IR. Median overall survival (OS) and event-free survival (EFS) in patients who achieved IR were 96 and 55 months versus 36 and 7 months in those who did not (p<0.001). Median OS and EFS were not reached and 59 months in the CR/IR group, 77 and 15 months in the noCR/IR, and 30 and 5 months in the noCR/noIR respectively (p<0.001 for both EFS and OS-fig.1). In univariate analysis, being in the CR/IR group was the only significant predictor for prolonged OS and EFS (p<0.001). Of note, cumulative incidence of extra-medullary disease at first relapse after the allograft was 4% in the CR/IR, 32% in the noCR/IR and 15% in the noCR/noIR groups respectively (p<0.001). Receiving the allograft as first line therapy or later during the disease course did not significantly impact on OS and EFS. Conclusion The achievement of IR confers a favorable impact on OS and EFS after allografting. A higher incidence of extra-medullary in the noCR/IR group (some 30% of our patient cohort) may suggest that myeloma cells escape immune control outside the bone marrow. In this group, imaging studies such as positron emission tomography may clinically be indicated during follow-up to detect early relapse. Disclosures: No relevant conflicts of interest to declare.

Acute Splenic Sequestration In a Newborn Cohort with Sickle Cell Anemia (SCA): Predictive Factors and Impact on Disease Severity

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 263-263 ◽  
Author(s):  
Cécile Arnaud ◽  
Annie Kamdem ◽  
Lena Coïc ◽  
Nadia Médejel ◽  
Emmanuelle Lesprit ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Severity ◽  
Predictive Factors ◽  
G6pd Deficiency ◽  
Conflicts Of Interest ◽  
Blood Parameters ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 263 Early occurrence of dactylitis, severe anemia and leukocytosis have been identified as risk factors for adverse outcome in children with SCA (Miller NEJM 2000), but the impact of acute splenic sequestrations (ASS) on disease severity has not yet been reported. The goal of this study was to define the predictive factors of ASS and to evaluate if this complication was a risk factor for disease severity. Methods. SS patients of the newborn cohort, seen at our SCA Center in Créteil before 3 months of age and older than 2 years at the last visit (n=197), were included in this study. Alpha and beta genotypes, and G6PD activity were determined. Blood parameters were recorded at steady state during the second year of life. ASS was defined as an Hb-decrease of ≥20% associated with a spleen-increase ≥2cm. Vaso-occlusive crises (VOC) requiring hospitalizations and acute chest syndromes (ACS) were recorded. The yearly rates of VOC and ACS were calculated for the entire follow-up and for the period before any intensification (transfusion program, hydroxyurea or SCT). Results. Median follow-up was 7.9 yr (range 2–24), providing 1820 patient-years. Alpha-Thal was present in 70/162 (43.2%); beta-haplotypes, available in 140 patients, were Car/Car in 62 (44.3%), Ben/Ben in 35 (25%), Sen/Sen in 7 (5%), and others in 34 (25.7%). G6PD deficiency was present in 24/171 (14%). At baseline, mean (SD) blood parameters were: Hb: 8g1/dL (1.2); Ht: 24.6% (3.9); MCV: 79.2 fL(8.3); HbF: 15.7% (8.2); LDH: 919 UI/L (369) and reticulocytes: 296 (114); WBC: 14.3 (5.2), neutrophils 5.8 (3.1) × 109/L. Among the 197 SS-patients, 64 (32%) experienced their first ASS at the median age of 2.0 yr (range 0.1–12.9) and 36/64 recurred. ASS occurred before 1 yr of age in 10 (5%) and before 2 yr in 33/197 (17%). Splenectomy was performed in 24 of them at the median age of 5.1 yr (range 2.7–12.9). The KM-estimated cumulative risk of ASS occurrence at age 7 was 32% (95%CI: 25–39%). The Cox-regression analysis showed that gender, G6PD deficiency, beta haplotypes were not risk factors whereas alpha-Thal significantly increased the risk of ASS occurrence (HR: 1.9, 95% CI:1.1-3.3, p=0.021). Among blood parameters, multivariate Cox analysis retained low platelet (HR: 1.4 per 1×107/L decrease; 95%CI:1.1-1.8, p=0.014) and high reticulocyte counts (HR=2.0 per 1×107/L increase; 95%CI:1.6-2.6) as independent significant predictive factors for ASS. Comparison of patients with or without ASS history showed no significant difference in the rate of ACS but significantly higher rates of VOC during the entire follow-up (0.68±0.58 vs 0.47±0.55; p=0.014) and in the number of hospitalizations (1.64±0.83 vs 1.29±0.92; p=0.01) in patients with ASS history. Rates of VOC before intensification were 1.1±0.7 and even 2.2±2.0 in those having experienced ASS before age 1 vs 0.6±0.7 (p=0.001) in those with no ASS history. Conclusion. Results from this study in a newborn cohort show that ASS are more frequent in patients with alpha-Thal and are associated with a higher rate of VOC. Splenectomy is usually recommended in case or recurrent ASS; however, our previous results show that geno-identical SCT can cure 95%SCA children and partly restore splenic function. We suggest that this procedure be proposed to those with available donor before considering total splenectomy. Disclosures: No relevant conflicts of interest to declare.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2959-2959
Author(s):  
Daisuke Ohgiya ◽  
Makoto Onizuka ◽  
Hiromichi Matsushita ◽  
Naoya Nakamura ◽  
Hiroshi Kawada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Chemotherapy Resistance ◽  
Nuclear Body ◽  
Rank Test ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2959 Background: Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods: Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results: The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion: Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. Disclosures: No relevant conflicts of interest to declare.

Impact of t (11;14) on the outcome of autologous hematopoietic cell transplantation (Auto-HCT) in multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8040-8040
Author(s):  
Koji Sasaki ◽  
Gary Lu ◽  
Chitra Hosing ◽  
Uday R. Popat ◽  
Sairah Ahmed ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Cancer Center ◽  
Induction Treatment ◽  
High Dose ◽  
Significant Difference ◽  
The Impact

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (>PR1: 82 vs. 76%, <PR1: 7 vs. 11%, relapsed 10 vs. 13%), complete remission (CR: 21% vs. 32%; p=0.30), very good partial remission (VGPR: 29% vs. 21%; p=0.23) or overall response (75% vs. 85%; p=0.18) between patients with t(11;14) and normal karyotype. Median PFS in patients with t(11;14) and normal karyotype was 15.7 months and 35.9 months, respectively (p=0.017). Median OS in patients with t(11;14) and normal karyotype was 51.4 months and 88.4 months, respectively (p=0.03). There was no difference in PFS (p=0.25) or OS (p=0.71) in patients with t(11;14), with or without other high-risk chromosomal abnormalities. Conclusions: In this large single center study with a long follow up, we demonstrated that t(11;14) in MM is associated with a shorter PFS and OS in the context of auto-HCT.

Variable Risk of Second Primary Malignancy In Multiple Myeloma Patients of Different Ethnicities

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 678-678
Author(s):  
Pedram Razavi ◽  
Gaurav Patel ◽  
Asher Chanan-Khan ◽  
Sikander Ailawadhi
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Latency Period ◽  
Incidence Rates ◽  
Second Primary ◽  
Solid Organ ◽  
Specific Patient ◽  
Significant Difference ◽  
Race Ethnicity ◽  
The Impact

Abstract Abstract 678 Background: Second primary malignancies (SPM) among multiple myeloma (MM) patients have been reported with an estimated incidence varying from 1%–15%. We have previously reported that significant disparity exists in MM survival across patients of different ethnicities. We undertook a Surveillance Epidemiology and End Results (SEER) based analysis to describe the incidence of SPM among MM patients of different ethnicities, in order to explore the variable impact that SPM might have on MM outcomes of patients across racial subgroups. Methods: SEER database was used to examine the standardized incidence rates (SIR) of SPM among MM patients diagnosed between 1973–2008. Observed to expected ratio (O/E) of SPM was calculated using incidence rates of cancers for the general population. The 95% confidence limits (CI) were constructed using Fisher's exact test. The analysis was restricted to patients with MM as first primary, microscopic confirmation of diagnosis, reporting sources not coded as autopsy- or death-certificate-only, and SPM reported more than 2 month after MM diagnosis. Mutually exclusive race/ethnicity categories were: African-Americans (AA), Asians/Pacific Islanders (API), Hispanic whites (HW), Non-Hispanic whites (NHW), and others. The risk of SPM among MM patients was explored by ethnicity, type of SPM, and latency period. Results: A total of 3090 cases of MM with SPM were diagnosed between 1973–2008, of which, 2021 patients met our inclusion criteria. Stratification of SPM by ethnicity revealed: 387 AA (19%), 72 API (4%), 51 HW (3%), 1500 NHW (74%) and 11 other (<1%) cases. There was an average 4.7-year latency period between diagnosis of MM and SPM (mean age 68.2 and 72.9 years, respectively). The latency period was not significantly different by type of SPM (solid organ vs. hematological) or ethnicity. AA had the youngest age at diagnosis for both, MM and SPM (65.6 and 70.1 year, respectively). (Figure 1) For all SPM sites analyzed together, there was no significant difference between the observed and expected incidence (O/E 0.98; 95% CI 0.94–1.02). However, O/E risk was significantly decreased for solid organ SPM (N=1695; O/E 0.92; 95% CI 0.88–0.96) and increased for hematological malignancies (N=263; O/E 1.63; 95% CI 1.44–1.84). Highest excess risk among all SPM was noted for acute non-lymphocytic leukemia (ANLL) (O/E 6.51; 95% CI 5.37–7.83). The overall risk of observed SPM was not different from expected rates by ethnicity, with the exception of HW who had a significantly decreased overall SPM risk. Table 1 summarizes significant results of O/E risk of SPM by race and site. HW and NHW were less likely to develop overall solid organ SPM. Within solid organ sites, HW had a significantly decreased O/E risk of developing lung/bronchus and prostate SPM. NHW were the only ethnic subgroup with an increased O/E risk of developing melanoma of skin, while the O/E risk of developing SPM of kidney/renal pelvis was increased only among AA. The risk of ANLL as SPM was significantly increased among AA, API, and NHW, while risk of NHL as SPM was only increased among NHW. Conclusion: Exploring potential causes of outcome disparities is important for evaluating disease characteristics and optimal triaging of healthcare resources for specific patient populations. We have performed the largest population-based analysis for the risk of SPM in MM patients stratified by race/ethnicity. We found that the risk of developing SPM among MM patients is variable depending on the patient's ethnic background. This warrants further exploration of the impact of SPM on outcomes of MM patients across different racial subgroups. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long Term Survival Analysis of Multiple Myeloma Patients Receiving Induction Therapy+ Autologous STEM CELL Trasplantation, Comparing Velcade-Dexametasone to Alkylating Polichemotherapy As Induction Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5764-5764
Author(s):  
Sara Caceres ◽  
Rocio Cardesa ◽  
Carmen Cabrera ◽  
M. Helena Bañas ◽  
Fatima Ibañez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Autologous Bone Marrow Transplantation ◽  
Young Patients ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
Term Survival ◽  
The Impact

Abstract Introduction: Multiple Myeloma (MM) is an incurable disease. In young patients, autologous bone marrow transplantation (ABMT) remains a cornerstone treatment after induction therapy. Induction therapy has varied during time, from alkylating polychemotherapy (VBAD,VCMP) or VAD chemotherapy (AVAD) to Velcade-Dexametasone based regimens (VD). We present results of follow-up of a large cohort of patients treated with ABMT. We described overall survival (OS; from transplant to death by any cause) and progression free survival (PFS; from transplant to death by any case or progressive disease defined by reappearance by inmunofixation, or duplication of monoclonal peak after ABMT) , and the impact of induction therapy regiments. Patients: 183 patients transplanted from 2002 to 2017. The median age of the patients was 59 years (33-72). Before 2008 all the patients were treated in alkylating based chemotherapy (42 patients). After 2008 patients were treated with VD based regimens (141patients). Only 12 patients received maintenance therapy based in PETHEMA trials 2005 and 2012. No one patient received a planed second transplant; only 32 patients received a second transplant after relapse as consolidation therapy. Results: Median follow-up of patients still alive is 3.65 years (0.15-14.77). Median OS of all patients was 9.12 years (95% confidence interval (CI): 6.28-NR); Median PFS was 3.02 years(95% CI: 2.46-3.76). At 13 years only 2% of patients remains progression free (CI: 0.00-17%). There were significant differences between patients treated before and after VD regimens. The median OS of patients treated with APVAD was significantly shorter compared to VD (6.22 years, CI[3.39-12] vs. NR, CI[6.28-NR], p=0.025) (HR=0.49, p=0.01). Conclusions: VD schemes of induction before ABMT have improved remarkably OS inpatients with Myeloma; nonetheless, plateau is not observed in EFS. Further analysis must address if EFS could represent a strong indicator of OS, mainly due to novel effective salvage therapies after relapse/refractoriness could be a confounding factor. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Improved Survival in African American Patients Undergoing Autologous Transplant for Multiple Myeloma in the Chemotherapy and Novel Agent Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4631-4631
Author(s):  
Karen Sweiss ◽  
Annie L. Oh ◽  
Gregory S. Calip ◽  
Damiano Rondelli ◽  
Pritesh R. Patel
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
African American ◽  
Proteasome Inhibitor ◽  
Conflicts Of Interest ◽  
Hematologic Toxicity ◽  
Racial Groups ◽  
Significant Difference ◽  
The Impact ◽  
Novel Agent

Abstract African Americans (AA) have a 2- to 3-fold higher incidence of multiple myeloma (MM) when compared to other racial groups. Evidence suggests that there may be differences in the biology of MM, which confer a more favorable prognosis in AA patients. Prior studies are conflicted as to whether AA patients achieve equal or improved outcomes compared to non-African American (non-AA) patients. Our purpose was to evaluate the impact of AA race on outcomes of MM patients undergoing ASCT at a single center in both the chemotherapy and novel agent era. One hundred and twenty-nine patients who received melphalan 200 mg/m2 and ASCT between 2000 and 2013 were included in the analysis. Sixty-one (47%) patients were African-American and 68 (53%) were non-AA. Baseline characteristics including age, FISH, cytogenetics, paraprotein subtype, median number of prior therapies and International Staging System (ISS) stage were similar between racial groups. Overall, 77 (60%) patients received any novel agent prior to transplant and 52 (40%) received only chemotherapy. More non-AA patients were male (59% vs. 38%, p=0.02), received initial induction with a proteasome inhibitor (59% vs. 28%, p=0.0007), and were treated with post-ASCT maintenance therapy (41% vs. 23%, p=0.008). Time from diagnosis to ASCT in AA patients was 10 (range: 4-144) versus 8 (range: 3-54) months in non-AA patients (p=0.01). The ASCT hospital course was similar between both groups with no significant differences in time to neutrophil and platelet engraftment as well as the duration of hospitalization. Additionally, there was no significant difference in the extra-hematologic toxicity between the two groups including the incidence of diarrhea, mucositis, and infection. Response was measured using the International Myeloma Working Group criteria and was assessed immediately prior to transplant and between 90 to 180 days after transplant. No differences were observed in pre-transplant (p=0.13) or post-transplant (p=0.28) response rates between the two groups. African American patients had a significantly improved median OS compared to non-AA patients (not reached vs. 108 months, p=0.03). We further stratified analyses of OS by those treated in the chemotherapy versus novel agent era. Improved OS was observed in both the chemotherapy (93 vs. 68 months, p=0.02) and novel agent (not reached vs. 79 months, p=0.01) treatment era. In a multivariate Cox proportional hazards model, AA race was associated with improved overall survival (adjusted HR 0.30, 95% CI 0.11 to 0.81; p=0.017). Multiple myeloma has one of the most apparent ethnic disparities in incidence and outcomes among cancers. In our study, AA patients had a longer time to transplant and received less proteasome inhibitor-based induction and post-ASCT maintenance suggesting disparities in access to care. Despite these differences in treatment, we observed improved overall survival after ASCT compared to non-AA patients. We demonstrated this improved OS in patients who had received either chemotherapy or novel agents prior to ASCT. These findings provide further evidence for more favorable outcomes among AA patients. One explanation could be a difference in disease biology that may result in a lower risk disease. Investigation of these biologic differences between AA and non-AA MM patients may increase our understanding of the pathogenesis and future treatments of myeloma. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic Factors in Patients with an Implanted Pacemaker after 80 Years of Age in a 4-Year Follow-Up

Gerontology ◽  
2017 ◽  
Vol 64 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Krystyna Krzemień-Wolska ◽  
Andrzej Tomasik ◽  
Celina Wojciechowska ◽  
Karolina Barańska-Pawełczak ◽  
Ewa Nowalany-Kozielska ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Favourable Prognosis ◽  
Treatment Type ◽  
Ventricular Lead ◽  
Pacing Mode ◽  
The Impact

Background: The controversy over electrotherapy for patients aged >80 years occurs already at the stage of qualification for this treatment type and concerns optimal device selection, the implantation strategy, and the overall benefit from pacemaker therapy. The group also has a considerable number of cardiovascular risk factors, and the data from the literature on the impact of the pacing mode on the remote prognosis of this group are ambiguous. Objective: Assessment of the risk factors for death among patients with implanted pacemakers >80 years of age in a 4-year follow-up. Methods: The study group consisted of 140 consecutive patients (79 women) aged 84.48 ± 3.65 years with single- or dual-chamber pacemakers implanted >80 years of age because of symptomatic bradycardia. In univariate and multivariate Cox regression analyses, demographic, echocardiographic, and laboratory parameters, pharmacotherapy, and factors related to the implanted device - i.e., indications, pacemaker type, and the implantation position of the tip of the right ventricular lead - were included. The endpoint was death for any reason in a 4-year follow-up. Results: During follow-up, 68 patients (48.6%) died. Although atrial fibrillation with a slow ventricular response constituted 20% of the indications for implantation, 60.8% of the patients received a single-chamber system (VVI/VVIR). In the whole group, the multivariate Cox regression analysis showed both a favourable prognostic significance of DDD pacing system implantation (HR = 0.507; 95% CI: 0.294-0.876) and coexisting hypertension (HR = 0.520; 95% CI: 0.299-0.902). The risk factors were fasting glycaemia (HR = 1.180; 95% CI: 1.038-1.342) and, potentially, female sex (HR = 1.672; 95% CI: 0.988-2.830; p = 0.056). In the female subgroup a more favourable prognosis was related to the use of angiotensin-converting enzyme inhibitors (HR = 0.435; 95% CI: 0.202-0.933) and DDD pacemaker implantation (HR = 0.381; 95% CI: 0.180-0.806). In the male subgroup a more favourable prognosis was related to concerned patients with coexisting hypertension (HR = 0.349; 95% CI: 0.079-0.689). Conclusions: DDD mode pacing seems to serve as a factor which decreases mortality among patients aged >80 years in long-term follow-up. The potentially poorer prognosis for the female patients in this group may result from a combination of the dominant VVI pacing mode, potential propagation of atrial fibrillation, a low proportion of antithrombotic therapy, and sex-related predispositions to thromboembolic complications.

scholarly journals The impact of native Fallot anatomy on future therapeutic requirements and outcomes at follow-up

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Ravaglioli ◽  
Lamia Ait-Ali ◽  
Duccio Federici ◽  
Stefano Salvadori ◽  
Arketa Pllumi ◽  
...  
Keyword(s):  
Interventional Procedures ◽  
Cox Regression ◽  
Interventional Procedure ◽  
Pulmonary Arteries ◽  
Cardiac Events ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Clinical Records ◽  
The Impact

Abstract Background In patients with repaired Fallot, subsequent surgical or interventional procedures and adverse cardiac events are frequent. We aimed to evaluate the impact of a simple pre-operative anatomic classification based on the size of the pulmonary valve (PV) annulus and branches on future therapeutic requirements and outcomes. Method This is a single-center retrospective analysis of patients operated for Fallot before the age of 2 years, from January 1990. Pre-operative anatomy, surgical and interventional procedures and adverse events were extrapolated from clinical records. Results Among the 312 patients, a description of the PV and pulmonary arteries (PAs) native anatomy was known in 239 patients (male:147, 61.5%), which were divided in the following 3 groups: group 1 (65 patients) with normal size of both PV and PAs; group 2 (108 patients) with PV hypoplasia but normal size PAs; group 3 (66 patients) with concomitant hypoplasia of the PV and PAs. During the 12.7 years (IQR 6.7–17) follow-up time, 23% of patients required at least one surgical or interventional procedure. At Kaplan–Meier analysis, there was a significant difference in requirement of future surgical or interventional procedures among the 3 groups (p < 0,001). At multivariate Cox regression analysis, hypoplasia of PV and PAs was an independent predictor of subsequent procedures (HR:3.1,CI:1.06–9.1, p = 0.03). Conclusion Native anatomy in Tetralogy of Fallot patients affects surgical strategy and follow-up. It would be therefore advisable to tailor patient’s counseling and follow-up according to native anatomy, rather than following a standardized protocol.

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