The Chronic Kidney Disease-Epidemiology Collaboration-Cystatin C (CKD-EPI-CysC) Equation Has an Independent Prognostic Value for Overall Survival in Newly-Diagnosed Patients with Symptomatic Multiple Myeloma: Comparison with 3 Other Equations for GFR Estimation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1849-1849
Author(s):  
Meletios A Dimopoulos ◽  
Efstathios Kastritis ◽  
Eirini Katodritou ◽  
Anastasia Pouli ◽  
Eurydiki Michalis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Cystatin C ◽  
Prognostic Value ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
P Value ◽  
Newly Diagnosed ◽  
Number Of Patients ◽  
Ckd Stage

Abstract Abstract 1849 Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The estimation of glomerular filtration rate (GFR) is based on equations that use serum creatinine (sCr) as a marker of RI (i.e. MDRD or CKD-EPI). The IMWG has recommended the use of the MDRD formula for the estimation of GFR in MM patients with stabilized sCr, while the classification of RI is based on the 5 stages of the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). However, the equations based on sCr are imprecise and thus novel markers of renal injury have been used in patients with renal damage, including cystatin-C (CysC). CysC is considered as a more sensitive marker of GFR than sCr. Recently, the CKD-EPI investigators have reported that a combined sCr-CysC (CKD-EPI-sCr-CysC) equation correlated better with GFR than equations based on either of these markers alone (CKD-EPI or CKD-EPI-CysC; Inker et al, NEJM 2012;367:20–9). Although cysC has been reported by our group to be elevated in MM patients, the CKD-EPI equations and their value on MM patients' survival have never been evaluated. Therefore, we studied 220 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years) and 16% had sCr ≥2 mg/dl. Serum CysC was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). Serum CysC was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, CKD-EPI, CKD-EPI-CysC and CKD-EPI-sCr-CysC equations were 63.45 ml/min/1.73m2, 68.13 ml/min/1.73m2, 68.11 ml/min/1.73 m2, and 64.87 ml/min/1.73 m2, respectively (p<0.01). Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 39.5% for MDRD vs. 42.2% for CKD-EPI vs. 43.1% for CKD-EPI-CysC vs. 45% for CKD-EPI-sCr-CysC (p<0.01; see also the table). Concordance for CKD stage allocation for the 4 equations of estimating eGFR was 97% for MDRD vs. CKD-EPI, 60% for MDRD vs. CKD-EPI-CysC and 84% for MDRD vs. CKD-EPI-sCr-CysC. A significant correlation was found between ISS stage and all studied equations (p<0.01 for all). The median overall survival (OS) for all patients was 52 months. In the univariate analysis per CKD stage, the 4 equations could predict for OS (the higher CKD stage had poorer survival) with the following significance: MDRD (p=0.057), CKD-EPI (p=0.01), CKD-EPI-CysC (p<0.0001), and CKD-EPI-sCr-CysC (p=0.006). When we tested the 4 equations as continuous variables, all had prognostic value for OS but the CKD-EPI-CysC had the strongest prognostic value (p<0.0001 and Wald=24.0 vs. p<0.0001 and Wald=19.7 for CKD-EPI-sCr-CysC, p=0.003 and Wald=8.9 for CKD-EPI and p=0.005 and Wald=7.7 for MDRD). In the multivariate analysis, that included ISS stage, LDH ≥300 U/l and eGFR for each different equation (as a continuous variable) only eGFR that included CysC but not sCr (CKD-EPI-CysC and not CKD-EPI-sCr-CysC) had independent significance (p=0.013) along with high LDH (p=0.029). Our data suggest that the CKD-EPI-sCr-CysC equation for the estimation of GFR detects more MM patients with stage 3–5 RI than the MDRD, CKD-EPI or CKD-EPI-CysC equations. However, CKD-EPI-CysC was the only equation that could predict for OS, possibly due to the very strong correlation of CysC with ISS (as myeloma cells produce CysC also). The confirmation of these data will lead to the broader use of equations based on CysC (CKD-EPI-CysC with or without sCr) for the evaluation of RI in patients with MM, as it has been suggested for patients with several other renal disorders. Table. Evaluation of Renal Function Stage by Different Equations CKD stage MDRD equation CKD-EPI equation CKD-EPI-CysC equation CKD-EPI-sCr-CysC equation p-value 1 60 (27%) 57 (26%) 67 (30%) 44 (20%) 2 73 (33%) 70 (32%) 58 (26%) 77 (35% Friedman-test 3 53 (24%) 55 (25%) 57 (26%) 62 (28%) p<0.01 4 21 (9.5%) 25 (11%) 27 (12%) 24 (11%) 5 13 (6%) 13 (6%) 11 (5%) 13 (6%) Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Lin Gui ◽  
Fei Wang ◽  
Jinning Shi ◽  
Baoan Chen
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Survival Time ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Rank Test ◽  
Newly Diagnosed

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR&lt;3.61) or high NLR group (NLR≥3.61), low MLR group (MLR&lt;0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR&lt; 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB&lt;100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB&lt;100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis. Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR Disclosures No relevant conflicts of interest to declare.

Prognostic Value of Syndecan-1 in Multiple Myeloma and its Relationship with Other Prognostic Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Type I ◽  
Newly Diagnosed ◽  
Clinical Markers ◽  
Free Survival

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P &lt;0.00001), labeling index (0.25; &lt;0.0001), creatinine (0.23; &lt;0.0001), soluble IL6 receptor (0.3; &lt;0.0001), BM plasma cell percentage (0.16; &lt;0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P &lt; 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P &lt; 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P &lt; 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.

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.

Increased Expression of Cyclin-D1 on Trephine Bone Marrow Biopsies Independently Predicts for Shorter Overall Survival In Patients with Multiple Myeloma Treated with Novel Agents

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2965-2965
Author(s):  
Evangelos Terpos ◽  
Maria Roussou ◽  
Anna Tasidou ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Plasma Cells ◽  
Univariate Analysis ◽  
Novel Agents ◽  
Positive Staining ◽  
Newly Diagnosed ◽  
Immunohistochemical Expression

Abstract Abstract 2965 The cyclin-D1 proto-oncogene is an important cell regulator of G1 to S phase progression. The overexpression of cyclin-D1 has been linked to the development and progression of several malignancies. The aim of our study was to evaluate the impact of the immunohistochemical expression of cyclin-D1on the plasma cells of trephine biopsies on survival of newly-diagnosed patients with multiple myeloma (MM) who were treated with novel agents. We evaluated formalin-fixed, paraffin-embedded, bone marrow sections of 130 consecutive patients with newly-diagnosed MM (67M/63F; median age 68 years) before any kind of therapy administration. One hundred and fifteen patients had symptomatic disease that required therapy: 29 (25%) received bortezomib-based regimens and 31 (26%) received thalidomide-based regimens as first line therapy, while all patients received regimens containing bortezomib or an IMiD at some point during the course of their disease. Immunohistochemistry was performed in all trephine biopsies using monoclonal antibodies against cyclin-D1 (Cell Marque Corp., Rocklin, CA, USA), but also against CD56 (Cell Marque Corp., Rocklin, CA, USA), CD27 (Novocastra, Newcastle upon Tyne, UK), CD117 and MUM-1 (DAKO A/S, Glostrup, Denmark), as recommended by the manufacturers. A case was considered positive if there was unequivocal positive staining of at least 20% of the plasma cells for cyclin-D1, CD56 and MUM-1 and a positive staining of at least 10% of the plasma cells for CD117 and CD27. Among patients with symptomatic myeloma (N=115), positive staining for cyclin-D1 was found in 35 (30%) patients, for CD56 in 45 (39%), for CD117 in 94 (81%) and for CD27 in 72 (62%) patients. In patients with asymptomatic myeloma, positive staining for Cyclin-D1 was found only in 1 (7%) patient, for CD56 in 9 (64%), and for CD117 in 6 (43%) (p<0.01 for all comparisons compared to symptomatic patients). There were significant positive correlations between positivity for CD27 and CD56 (p<0.001), between positivity for cyclin-D1 and CD117 (p=0.045) and a negative correlation between positivity for CD117 and CD56 (p=0.001). We also observed significant correlations between CD56 positivity and ISS-1 or ISS-2 (p=0.01) and between CD117 positivity and ISS-3 disease (p=0.002). The median overall survival (OS) for patients with symptomatic MM was 57 months (range 22–120 months). In the univariate analysis, positivity for cyclin-D1 (41 vs. 62 months, p=0.03) and for CD117 (50 vs. 75 months p=0.018) were associated with inferior survival, while positivity for CD56 (47 vs. 62 months, p=0.286), MUM-1 (52.7 vs. 63.8 months, p=0.528) and CD27 (57 vs. 50 months, p=0.445) were not. Other factors associated with inferior OS, in the univariate analysis, included ISS-3 (median OS 37 months, vs. 57 months for ISS-2 and 73 months for ISS-1, p=0.005), Hb <10 g/dl (56 vs. 73 months, p=0.044), corrected serum calcium >11.5 g/dl (29 vs. 62 months, p=0.02), serum LDH above upper normal limit (31 vs. 61 months, p=0.05), serum creatinine >2 mg/dl (26 vs. 64 months, p=0.007), low platelet counts (<100,000/ml) (22 vs. 62 months, p=0.031) and age >65 years (45 months vs. not reached for younger patients, p=0.002). In the multivariate analysis, positivity for cyclin-D1 (HR: 2.6; p=0.001), ISS stage (HR: 1.8; p=0.001) and age >65 (HR 2.7, p=0.003) were independently associated with inferior survival. Immunohistochemistry for cyclin-D1 identified subgroups of patients in ISS-2 and in ISS-3 who had extremely poor outcome. Patients with cyclin-D1 positivity had a median survival of 22 months in ISS-2 (vs. 64 months for the rest of ISS-2 patients, p=0.01) and of 13 months in ISS-3 (vs. 47 months for the rest of ISS-3, p=0.012). Our findings underline that the immunohistochemical expression of cyclin-D1 in the bone marrow trephine biopsies has independent prognostic value in MM patients, even in the era of novel agents. This marker can easily be assessed in patients who undergo a trephine biopsy as part of their initial evaluation and offers significant prognostic information. Furthermore, novel agents targeting cyclin-D1 may be of therapeutic value in MM. Disclosures: No relevant conflicts of interest to declare.

A Better Mobilization Regimen for Newly Diagnosed Multiple Myeloma Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4051-4051
Author(s):  
Ahmed Y Abuabdou ◽  
Eric R Rosenbaum ◽  
Saad Usmani ◽  
Bart Barlogie ◽  
Michele Cottler-Fox
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Optimal Number ◽  
P Value ◽  
Newly Diagnosed ◽  
The Poor ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Minimum Number ◽  
Poor Mobilizer

Abstract Abstract 4051 Introduction: What constitutes an acceptable mobilization regimen for collecting CD34+ cells depends on whether the goal of collection is to obtain a minimum number versus optimal number of cells. When treating patients with high-risk myeloma it may be important to obtain an optimal number. Here we compare retrospectively our earlier mobilization regimen, VTD-PACE, with MVTD-PACE in newly diagnosed, previously untreated multiple myeloma patients. Materials and Methods : We reviewed data for all patients who collected hematopoietic progenitor cells on Total Therapy protocols TT3a/TT3b with VTD-PACE (n=394) from February 2004 to September 2008 (138 females and 256 males, median age 59y; range 31–75), and on TT4/TT5 with MVTD-PACE (n=188) from August 2008 to May 2011 (78 females and 110 males, median age 61y, range 30–76). Based on their predicted first day collection with a large volume leukapheresis (30L processed), using our center's predictive formula (Blood 2010; 116(21):1182a), patients were stratified into 4 mobilizer types: poor (<2×106 CD34+ cells/kg), intermediate (≥2 to 10×106), good (>10 to 20×106) and excellent (>20×106). Variables examined included number of CD34+ cells/μl blood on day 1 and day 2 of collection (we have a minimum 2 day collection requirement), number of collection days to reach our minimum goal of 20×106 CD34+ cells/kg, and total CD34+ cells/kg collected for both chemotherapy groups. Variables for both groups stratified by mobilizer type were compared using two-tailed student's t-tests, except for the poor mobilizer group, where population size was too small for formal statistical analyses (VTD-PACE n=7, MVTD-PACE n=4), although averages were calculated. Results : There was no significant difference between VTD-PACE and MVTD-PACE for CD34+ cells/μl blood on day 1 of collection among the excellent [mean 368.9 (n=184) vs. 434.6 x106 (n=92); p-value 0.07], good [mean 138.6 (n=102) vs. 128.6 x106 (n=40); p-value 0.19], and intermediate [mean 60.1 (n=100) vs. 55.9 x106 (n=52); p-value 0.39] groups. A statistically significant difference between VTD-PACE and MVTD-PACE was found for CD34+ cells/μl blood on day 2 of collection for excellent mobilizers [mean 333.8 (n=184) vs. 460 ×106 (n=92); p-value <0.001], but not for the good [mean 165.7 (n=102) vs. 189.5×106 (n=40); p-value 0.21] and intermediate [mean 80.1 (n=101) vs. 102.3 ×106 (n=52); p-value 0.07] groups. When CD34+ cell/kg collection totals with VTD-PACE and MVTD-PACE were compared, a significant difference was seen for the intermediate mobilizer group only [mean 23.6 (n=101) vs. 26.3 ×106 (n=52); p-value 0.03]. For the poor mobilizer group, VTD-PACE had an average CD34+ cells/μl blood of 13.5×106 for day 1 of collection and 17.0 ×106 for day 2, with a total of 14.5×106 CD34+cells/kg collected; while MVTD-PACE had an average of 13.2×106 CD34+ cells/μl blood for day 1 of collection, 24.9×106 for day 2, with a total of 24.2×106CD34+ cells/kg collected. The number of collection days was similar between VTD-PACE and MVTD-PACE in the excellent mobilization group (2 days), but was slightly more for VTD-PACE compared to MVTD-PACE for the good (2.1 vs. 2 days), intermediate (3.2 vs. 2.9 days), and poor (6.1 vs. 5.8 days) groups. Conclusion : Both regimens allow more than minimum collections, but MVTD-PACE provides a higher peak number of CD34+ cells/μl blood, resulting in a slightly lower mean number of days of collection than VTD-PACE to reach an optimal collection. Disclosures: No relevant conflicts of interest to declare.

Multiple Copies of MLL Is The Most Commonly Detected Cytogenetic Abnormality In Newly Diagnosed Multiple Myeloma and May Modify Disease Risk

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1910-1910 ◽  
Author(s):  
Chrystal Landry ◽  
Dory Londono ◽  
Sean M. Devlin ◽  
Alex Lesokhin ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Protein Translation ◽  
Response To Therapy ◽  
Cytogenetic Abnormality ◽  
Newly Diagnosed

Abstract Background Multiple myeloma (MM) is a heterogeneous condition with variable disease course, response to therapy, and survival outcome. Cytogenetics and fluorescent in-situ hybridization (FISH) have identified several recurrent chromosomal aberrations in MM and play important and independent roles in risk stratification (Munshi et al. Blood 2011). However, the pathogenesis of the disorder remains poorly understood. Next-generation sequencing has recently identified that MM involves mutations of genes with roles in protein translation, histone methylation, and blood coagulation (Chapman et al. Nature 2011). Based on the observation that extra copies of MLL, a histone methyltransferase known to regulate the homeotic transcription factor HOXA9 that is highly expressed in MM, is frequently detected in MM, we sought to define the incidence and prognostic significance of excess MLL in MM patients. Methods We identified 188 patients with newly diagnosed MM who had cytogenetics and/or FISH performed on initial, pre-treatment bone marrow specimens at Memorial Sloan-Kettering Cancer Center between January 2009 and December 2012. Standard karyotype and FISH were performed as previously described (Cigudosa et al. Blood 1998, Gerritsen et al. Blood 1992). Probes included LSI IgH/FGF3, LSI IgH/CCND1, LSI IgH/MAF, LSI MLL, LSI p53/cep17, LSI13q14.3/13q34, LSI ETV6, LSI CBFB, LSI 1p36/1q25, and LSI 5,9,15 from Abbott Molecular. Fisher's exact test evaluated the association between MLL and selected abnormalities. Kaplan-Meier methodology estimated overall survival from the date of BM evaluation, and survival was compared using a logrank test. Results In unselected bone marrow specimens, abnormalities were detected by karyotype in 17% (27/156) and FISH in 47% (87/186) of patients tested. Hyperdiploidy, which has been associated with longer survival, was identified in 23% (43/187) of patients, while the unfavorable risk abnormalities, including loss of p53, deletion 13q (by karyotype), translocation (4;14) and excess 1q were seen in 8% (15/179), 8% (12/156), 4% (7/176) and 16% (29/178) of patients, respectively. Translocation (11;14) was seen in 4 patients; translocation (14;16) was not identified in any patient. 28% (51/183) of patients had extra copies of MLL, which was the most frequent genetic abnormality identified. Unexpectedly, this abnormality was significantly associated with both favorable (hyperdiploidy, P = <0.001) and unfavorable (deletion 13q, P = 0.043; excess 1q P = 0.001) risk genetics. While having excess MLL had no impact on the overall survival of standard-risk patients, defined as neither hyperdiploid nor with unfavorable genetics (N = 100), patients with poor-risk genetics (N = 46) and extra copies of MLL had a trend toward better survival, P = 0.06 (Figure 1). Conclusions Karyotype and FISH studies identified excess MLL as the most frequent cytogenetic abnormality in a large cohort of newly diagnosed MM patients. In patients with MM and unfavorable cytogenetics, the presence of excess MLL may ameliorate some of the adverse impact of associated with these abnormalities. Understanding the functional significance of excess MLL, perhaps as it relates to frequently dysregulated HOXA9 in MM, may provide insight into disease pathogenesis and/or identify drugable targets. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Original Versus Generic Lenalidomide in Patients with Relapsed Multipl Myeloma: Comprasion of Effectivity and Adverse Events

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5594-5594
Author(s):  
Zahit Bolaman ◽  
Sehmus Ertop ◽  
Atakan Turgutkaya ◽  
Selim Cem ◽  
Ayse Hilal Eroglu Kucukerdiler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Muscle Cramp ◽  
P Value ◽  
Medicine Department ◽  
School Of Medicine ◽  
Number Of Patients

Original versus generic lenalidomide in patients with relapsed multipl myeloma: Comprasion of effectivity and adverse events Ali Zahit Bolaman1, Sehmus Ertop2 Atakan Turgutkaya1, Cem Selim, 1 Ayse Hilal Eroglu Kucukerdiler1, Birsen Sahip2, Irfan Yavasoglu1. 1 Adnan Menderes University, School of Medicine, Department of Hematology AYDIN/TURKEY 2 Bulent Ecevit University School of Medicine, Department of Hematology ZONGULDAK/TURKEY Backround: Lenalidomide is an effective IMID derivative drug in the treatment of patients with multiple myeloma. Lenalidomide is available as original and generic forms in our country. So far, there is no any clinical study comparing generic and original lenalidomine for effectivity and adverse events. We compared generic and original lenalidomide effects and adverse events (AEs) in patients with relapsed multiple myeloma (RMM). Methods: The patients with RMM using original or generic lenalidomide were evaluated as retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease and progressive disease rates and also for adverse events, development rates of neutropenia, anemia, thrombocytopenia, febrile neutropenia, anorexia, constipation diarrhea, nausea, vomiting, creatinine increase, transaminase increase, asthenia, fatigue, pyrexia, peripheral edema, upper respiratory system infection, pneumonia, another infection, muscle cramp, back pain, bone pain, muscle weakness, arthralgia, headache, tremor, paresthesia, deep vein thrombosis, pulmonary embolism, hyperglycemia, hypokalemia, hypocalcemia, hypomagnesaemia, skin dry and skin erythema were investigated in myeloma patients. All data were analyzed using the PASW for Windows version 19.0 (SPSS Inc., Chicago, IL, USA). The results were described as a number, frequency, and percentage. The chi-squared test and Fisher's exact test were used for the analysis of categorical data and independence between variables. The results were assessed at 95% confidence interval and p-value of less than 0.05 was accepted as significant. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. OR rate was 60 % versus 39.5% in patients using original and generic lenalidomide, respectively. CR rate was 14.5%, VGPR was rate 45.4% in original group while CR rate was 20.9 and VGPR 18.6 in patients using generic lenalidomide. AEs were low in original lenalidomide group than generic group. AEs were usually grade 1 or 2. Response and AEs rates are shown in Table 1. Conclusion: Our study showed original and generic forms of lenalidomide are effective for the treatment of RMM. OR rate was higher in original lenalidomide than generic lenalidomide. The AEs of original lenalidomide were lower than generic lenalidomide without statistically significance. Further studies involving a larger number of patients with RMM would be useful for comparing the efficacy and AEs of original or generic lenalidomide. Disclosures No relevant conflicts of interest to declare.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin-C Are Sensitive Markers of Renal Injury in Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3918-3918
Author(s):  
Evangelos Terpos ◽  
Gerasimos-Petros Papassotiriou ◽  
Efstathios Kastritis ◽  
Maria Gkotzamanidou ◽  
Dimitrios Christoulas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Serum Creatinine ◽  
Cystatin C ◽  
Renal Damage ◽  
Roc Analysis ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Mdrd Formula ◽  
Neutrophil Gelatinase

Abstract Abstract 3918 Renal impairment (RI) is a common complication of patients with multiple myeloma (MM). The evaluation of RI is based mainly on the estimation of glomerular filtration rate (GFR) using the MDRD equation. However, MDRD formula has greater value in patients with stabilized serum creatinine, while the majority of MM patients have acute renal damage. Thus, it is of great importance to evaluate novel markers of kidney injury in MM setting. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 KDa protein which is overproduced by proximal tubular cells in response to injury. NGAL is upregulated within 2 hours of injury, well before functional changes are observed in both preclinical and clinical studies. NGAL has never been evaluated in MM. Cystatin-C (Cys-C) is a cysteine protease inhibitor which provides a better reflection of GFR (renal tubular function) than serum creatinine. The aim of the study was to evaluate NGAL and Cys-C in MM and explore possible correlations with patients' RI. We studied: i) 64 patients with newly diagnosed myeloma: 16 with asymptomatic disease (7M/9F; median age 59 years, range 37–82 years) and 48 with symptomatic myeloma (30M/18F; median age 70 years, range 45–89 years; ii) 8 patients with MGUS (4M/4F; median age 72 years, range 39–84 years); and iii) in 20 healthy, gender and age-matched controls. Serum Cys-C was measured on the Behring Nephelometer-II analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany). Serum NGAL was measured using an ELISA methodology (Quantikine, R&D Systems, Minneapolis, MN, USA). eGFR was evaluated using the MDRD formula. Twenty-six (54%) patients with symptomatic MM had eGFR >60 ml/min, while 12 (25%) had eGFR 30–60 ml/min and 10 (21%) eGFR <30 ml/min. All patients with asymptomatic MM and MGUS had an eGFR >60 ml/min. However, NGAL serum levels were elevated in patients with both asymptomatic (median: 91.7 μg/l, range: 29.5–206.4 μg/l) and symptomatic MM (115.4 μg/l, 15.4–417.3 μg/l) compared to controls (52.5 μg/l, 26.5–72.6 μg/l; p<0.001 for both comparisons). Even MGUS patients had elevated NGAL values compared to controls (116.5 μg/l, 74.9–205.5 μg/l; p<0.01). Only patients with symptomatic MM had increased levels of Cys-C compared to controls (1.37 mg/L, 0.7–4.0 mg/l vs. 0.7 mg/l, 0.6–1.0 mg/l; p<0.01). NGAL strongly correlated with Cys-C (r=0.506, p<0.001) and eGFR (r=-0.457, p<0.01), while Cys-C showed also strong correlation with eGFR (r=-0.804, p<0.001) as well as with ISS (ISS-3 had higher values of Cys-C compared to ISS-2 and ISS-1, p-ANOVA<0.001), beta2-microglobulin (r=0.434, p=0.002), high sensitivity CRP (r=0.364, p=0.012), serum interleukin-6 (r=0.349, p=0.016) and age (r=0.339, p=0.019). Regarding eGFR, the median levels (range) of NGAL were 97.8 μg/l (17.5–244.2 μg/l), 151.2 μg/l (15.4–232.3 μg/l) and 233.4 μg/l (101.7–417.3 μg/l) for patients with eGFR >60 ml/min, 30–60 ml/min and <30 ml/min, respectively (p-ANOVA<0.001). The respective median values for Cys-C were: 0.9 mg/l (0.7–2.0 mg/l), 1.5 mg/l (1.1–3.2 mg/l) and 2.9 (1.7–3.9 mg/l) for patients with eGFR >60 ml/min, 30–60 ml/min and <30 ml/min (p-ANOVA<0.001). The ROC analysis showed that NGAL values of >50.5 μg/l have a 80.8% sensitivity and 86.4% specificity for eGFR <60 ml/min (AUC=0.764). Similarly, Cys-C values of >1.15 mg/l have a 73.1% sensitivity and 100% specificity for eGFR <60 ml/min (AUC=0.941). Median levels of Cys-C were higher in patients with BJ proteinuria ≥200 mg/day (1.6 mg/l, 0.7–3.9 mg/l) compared to all others (1.1 mg/l, 0.7–1.9 mg/l; p=0.003). The respective values of NGAL for patients with BJ proteinuria ≥200 mg/day vs. <200 mg/day were: 169.7 μg/l (15.4–417.3 μg/l) vs. 105.5 μg/l (35–212.7; p=0.099). The ROC analysis showed that NGAL values of >61.7 μg/l have a 76.9% sensitivity and 81% specificity for BJ proteinuria ≥200 mg/day (AUC=0.641), while Cys-C values of >1.5 mg/l have a 92.3% sensitivity and 76.2% specificity for BJ proteinuria ≥200 mg/day (AUC=0.941). Our data suggest that both NGAL and Cys-C are very sensitive markers that reflect RI in newly-diagnosed patients with multiple myeloma. The high levels of NGAL in asymptomatic MM patients and in MGUS patients may indicate the presence of subclinical renal damage in these patients early in the course of their disease and may reveal NGAL as an early marker that predicts the development of RI in MM. Disclosures: No relevant conflicts of interest to declare.

Cytometric Response in Multiple Myeloma Cells to Low and Standard Doses of Bortezomib

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5393-5393
Author(s):  
Nicole Beffermann ◽  
Mauricio Ocqueteau ◽  
Pablo Ramirez ◽  
Mauricio Galleguillos ◽  
Mauricio Sarmiento
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Overall Survival ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Light Chains ◽  
Cell Transplant ◽  
Antineoplastic Drugs ◽  
Low Doses ◽  
Number Of Patients

Abstract Bortezomib is a very useful drug in the treatment of multiple myeloma (MM) patients. Used in combination with other antineoplastic drugs it has a well documented impact in progression free survival (PFS) and overall survival (OS) of any age patients, elegible or not for hematopoietic cell transplant. Standard dose (1,3 mg/m2) is used in almost all patients and low dose (0,7-0,8mg/m2) is reserved to patients with kidney disease and neuropathy. However, bortezomib doses used in phase 1 and 2 initial studies were described between 0,7 and 1,3 mg/m2 and were equally effective. The aim of this study was to evaluate the cytometric response of MM naive patients to two different bortezomib doses. We retrospectively analyzed the flow cytometry of fourty eight patients with naive MM treated with VCD scheme (Bortezomib-Cyclophosphamide-Dexametasone), without kidney failure nor neuropathy, of whom 21 received low doses of bortezomib (0.8mg/m2) and 27 standard doses (1.3 mg/m2). Flow cytometry was analyzed at diagnosis and at the end of treatment according to the expression of several clusters of differentiation (CD), establishing the presence of plasmoblastic myeloma clones (>95% of plasma cells with immunophenotype CD19 (-) CD56(+) CD45(-) CD38(+) and restriction of intra cytoplasmatic kappa and or lambda light chains) and normal mature plasma cells (CD19(+) CD56(-) CD45 (+) CD38 (++) with a policlonal expression of kappa/lambda light chains). Cytometric complete response was defined as normalization of the immunophenotype of plasma cells and absence of pathological cells. We found no statistical differences between the 2 groups in flow cytometric response (p>0.1), as shown in figure 1. This retrospective analysis suggests that lower doses of bortezomib could have similar effects in disease control, at least in cytometric response, to standard doses. Further studies should be made to evaluate clinical response and overall survival in patients treated with low doses compared to standard doses of bortezomib. In our country high costs of new generation antineoplastic drugs makes it necessary to find less expensive and equally effective schemes in order to make these well known beneficial treatments available to a greater number of patients. Disclosures No relevant conflicts of interest to declare.

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