FLC Assay and Multiparameter Flowcytometry Based Clonal Plasma Cell Measurement Are Independent but Complementary in Assessing the Treatment Response in Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2969-2969
Author(s):  
Hiroki Sugihara ◽  
Kenji Tsuda ◽  
Tomotaka Ugai ◽  
Yuki Nishida ◽  
Masayuki Yamakura ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Partial Response ◽  
Plasma Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Response To Treatment ◽  
Rank Test ◽  
Multiparameter Flow Cytometry ◽  
Prognostic Impact

Abstract Abstract 2969 Purpose: Although stringent complete response (sCR) defined by paraprotein negativity on immunofixation and serum free light chain (sFLC) ratio normalization are considered deeper responses in the IMWG criteria, recent report indicated that Multiparameter flow cytometry (MFC)-dased immunophenotypic response (IR) is a more relevant prognostic factor in MM patients. However, data on the prognostic impact of IR and sFLC ratio (sFLCκ/λ) normalization are still scarce. We investigated the prognostic impact of IR and sFLCκ/λ normalization in MM patients treated with novel agents. Patients and Methods: A total of 124 consecutive patients (M:F=68:56; median age, 71 yr) were treated by chemotherapy regimens containing at least one novel agent (thalidomide, bortezomib, lenalidomide)from April 2005 to May 2012. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the clinical course was assessed by simultaneous serum immunofixation, sFLC measurements, and MFC analysis of bone marrow (BM) plasma cells. Normalization of sFLCκ/λ was defined 2 consecutive normal sFLCκ/λ apart from at least 4 weeks. MFC-defined minimal residual disease (MRD) was evaluated by single-tube 6-color MFC, CD45-CD38 gating strategy, and combination CD19, CD56, and cytoplasmic κ-λ analysis. Clonal plasma cell (PC) negativity by MFC (MFC-negative) was defined as <10−4 neoplastic PCs in BM samples on MFC. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan–Meier (K-M) method and differences between curves were calculated by two-sided log-rank test. Univariate analysis was used to assess the impacts of factors on sFLCκ/λ normalization and MFC negativity (age, Durie–Salmon stage, ISS stage, LDH, hemoglobin, serum albumin, serum creatinine, FISH at diagnosis). The Cox regression proportional hazard model (stepwise regression) was used to explore the independent effects of these variables on PFS and OS. Results: At a median follow-up of 25.8 months, 3- and 5-year OS of all patients were 61.0% and 42.4%, respectively. CR was obtained in 25% (31/124), very good partial response (VGPR) in 33.5% (41/124), partial response (PR) in 30.5% (38/124), and stable disease or less (SD) in 11% (14/124). Normal sFLCκ/λ was achieved in 81% of CR, 56% of VGPR, 13% of PR, and 0% of SD or less response of patients. K-M estimated 3- and 5-year OS were 100% in CR patients; these were significantly better than in VGPR (75.8% and 43.2%, respectively) and PR patients (63% and 26.7.%, respectively). There were no significant differences in 3- or 5-year OS between VGPR and PR patients. Normal sFLCκ/λ and MFC negativity were achieved in 25 (81%) and 18 (58%) of 31 CR patients, respectively. Among 25 CR patients with normal sFLCκ/λ (stringent CR), 15 (60%) were MFC-negative and 10 (40%) were MFC-positive; three of 6 CR patients (50%)without normal sFLCκ/λ were MFC-positive. Twenty-three of 41 VGPR patients (56%) obtained normal sFLCκ/λ, while only 5 (12%) became MFC-negative; all 5 MFC-negative patients also obtained normal sFLCκ/λ. Among 52 patients with less than PR, only 5 (9.6%) obtained normal sFLCκ/λ and none achieved MFC negativity. Patients with MFC-negative CR showed significantly better PFS than patients with MFC-positive CR (p<0.05). Although patients in stringent CR with MFC-negative showed slightly better PFS compared to patients in stringent CR with MFC-positive, difference between the curves were not significant. Within the group of VGPR, PFS and OS were significantly longer in normal sFLCκ/λ patients than abnormal sFLCκ/λ(P<0.001). Univariate analysis showed that hemoglobin 10.0 g/dl>, age >70 yr, and abnormal LDH had negative prognostic impacts on attaining normal sFLCκ/λ, but none of these factors remained significant on multivariate analysis. Cox analysis showed that sFLCκ/λ normalization was an independent prognostic factor for longer PFS and OS in patients with CR, VGPR and PR (P=0.001). Conclusions: This study confirmed that magnitude of CR and VGPR response defined by IMWG criteria was heterogeneous in terms of sFLCκ/λ normalization and MFC negativity. Although MFC and sFLC analysis frequently gave discrepant results among patients with CR and VGPR, both analyses appeared to give important complementary information for assessing the depth of CR and VGPR category. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact Of Comorbidity In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5340-5340 ◽  
Author(s):  
Rafael Ríos Tamayo ◽  
Joaquín Martínez López ◽  
Manuel Jurado ◽  
María Esther Clavero Sánchez ◽  
Fátima López Jiménez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Plasma Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Alcoholic Fatty Liver

Abstract Multiple myeloma (MM) is a heterogeneous disease. Evaluation of prognostic factors and risk stratification at diagnosis is necessary to compare outcome. Attempts have been made to apply a comorbidity score in the clinical sitting, but a standardized general approach is still lacking. We hypothesized that a comprehensive examination of every associated disease in a large cohort of patients could better highlight the prognostic impact of comorbidity in MM. All consecutive patients diagnosed in our institution, from 1993 to 2013, with symptomatic MM according to IMWG criteria were included in our population-based MM registry. Patients with plasma cell leukemia or with palliative management were excluded. Clinical variables analyzed were: age, sex, Durie-Salmon, International Scoring System (ISS), percentage of plasma cell in bone marrow by morphology (PC), serum creatinine (Cr) and estimated glomerular filtration rate according with Modification of Diet in Renal Disease (eGFR-MDRD). The following comorbodities were analysed: hypertension (HTA), diabetes (DM), obesity (OB) (body mass index > 30 Kg/m2), hyperlipaemia (HL), prior malignancy (PM), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), peptic ulcer (PU), thromboembolism (TE), renal transplant (RT), splenectomy (S), cutaneous disease (CD), amyloidosis (AM), heart disease (HD) (arrhythmia, congestive heart failure, coronary artery disease, other), lung disease (LD) (chronic obstructive pulmonary disease, asthma, other), liver disease (HE) (cirrhosis, non-alcoholic fatty liver disease, other), neurological disorder (ND), psychiatric disorder (PD) and rheumatologic disorder (RD). Kaplan-Meier method was used to estimate OS curves. Cox regression was used to determine the prognostic impact of each comorbidity in a univariate and multivariate model. 311 patients were eligible. Median age was 66 years (12-91), 148 men (47.6 %) and 163 women. Percentage of comorbidities was: HTA 45; OB 32.5; DM 20.4; HD 20.4; LD 15.2; PU 10; HL 9.7; ND 8; PM 7.8; PD 6.5; HBV 3.9; HE 3.9; TE 3.6; RD 3,5; AM 2.3; HCV 1.9; CD 1.6; S 1; RT 0.6; HIV 0.3. 63 patients (20.4 %) showed no comorbidities. Univariate analysis (table 1) demonstrated that AM (P=0.022), HCV (0.038), HIV (0.022), PD (0.015) and ND (0.05) were significantly associated with shorter OS. The variables associated with mortality in the multivariate analysis were age (p=0.002), ISS (III vs I: p=0.01), PC (p=0.05) and Cr (p=0.02). Results will be validated in another MM series and presented during the meeting. The overall prognosis of MM depends on a variety of host and disease-related characteristics. We confirm age, ISS, PC and Cr as robust and independent prognostic factors. Adjusting for these factors, no isolated comorbidity reach statistical significance; however, comorbidity seems to have a role in MM prognosis. More studies are warranted to define the prognostic impact of comorbidities in MM. Disclosures: No relevant conflicts of interest to declare.

High Resolution Array-CGH Provides New Insights Into the Prognosis of Chronic Lymphocytic Leukemia (CLL): Is 8p Loss Worse Than 17p Loss?.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2339-2339
Author(s):  
Andrea Rinaldi ◽  
Michael Mian ◽  
Davide Rossi ◽  
Francesco Forconi ◽  
Clara Deambrogi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Rank Test ◽  
Western World ◽  
Clinical Parameters ◽  
Log Rank Test ◽  
The Impact

Abstract Abstract 2339 Poster Board II-316 BACKGROUND: CLL, the most common adult-onset leukemia in the Western world, has a heterogeneous clinical course. Many advances have led to a better understanding of its pathogenesis and to improvements in treatment strategies, but striking solutions are still missing. We conducted a study to evaluate the impact of genomic aberrations on the clinical course. METHODS: From January 1980 to May 2008, 395 frozen samples of CLL patients, were prospectively collected in four centers. Extracted DNA was analyzed with Affymetrix Human Mapping 6.0 arrays. Normal matched DNA was analyzed for one fourth of the cases. Correlations between minimal common regions (MCR) and clinical parameters were evaluated with the Fisherôs-exact test and their impact on OS with the log-rank test. A p-value after Bonferroni multiple test correction (MTC) (p-adj.) <0.05 was considered as statistically significant. Up to now 266 samples have been analyzed. RESULTS: Analysis of the clinical parameters (CPs) and known risk factors (Rai/Binet, age, doubling time, LDH, beta2, IGVH status, p53 mutations, telomere length, CD38, 11q, 17p) was consistent to previous published series. ZAP70 did not affect the clinical course, likely due inter-laboratories variability. After a median follow up of 53 months, 143/239 (60%) of the patients have started therapy and 63/261 (24%) died. 5-yr OS was 82%. Fisher test between the MCRs and CPs revealed an inverse relation between the presence of trisomy 12 by FISH and del13q14.3, an association between del17p and losses of 8p regions and between CD38 and 12q gain. Before MTC, 46 MCRs had a significant impact on OS and 67. After MTC, 3 regions maintained their role: 8p22 loss (38/248, 15%, p-adj.=0.002, median OS: 26 months vs. 48), 17p13.3-11.2 loss (20/248, 8%, p-adj.=0.001; median OS: 10 months vs. 48). In univariate analysis, the log-rank test among pts with 8p-/17p- (8/248, 3%), 8p- (30/248, 12%), 17p- (12/248, 5%), wild type (198/248, 80%) was statistically significant (p<0.001; see figure). Importantly, none of the analyzed clinical and biological parameters was associated with this aberration. CONCLUSIONS: Loss of 8p22 designated a CLL subgroup with a worse outcome among all patients and in the subset with 17p loss. Our data suggested that this aberration might constitute an independent prognostic factor to be evaluated in independent studies. Results, including a Cox regression model, will be presented on all 395 cases. Disclosures: No relevant conflicts of interest to declare.

Cetuximab (CTX) in first-line treatment of elderly patients with metastatic colorectal cancer (mCRC), KRAS wild type: French multicentre prospective community-based registry and results.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 760-760
Author(s):  
Laurent Mineur ◽  
Eric François ◽  
Jean Marc Phelip ◽  
Rosine Guimbaud ◽  
Carine Plassot ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rank Test ◽  
Wild Type ◽  
Community Based ◽  
Cox Models ◽  
Cox Regression Analysis ◽  
Effective Age

760 Background: Pts included in clinical trials represent the unusual population in mCRC. This study aims to provide oncologist with a better understanding of the potential benefit of CT with CTX in older patients with mCRC KRAS wild type and evaluate prognostic variables on the PFS including the age. Methods: Premium cancer study is a French multicentre prospective community-based registry. 493 pts enrolled and 487 included between September 2009 to March 2012 from 94 French centers and physicians. Pts had to provide written informed consent and protocol submitted to regulatory authorities. Predefined efficacy endpoints was PFS. CTX was administrated at 250 mg/m2 weekly (n=100; 20.3%) or 500 mg/m2 every 2 weeks (n=380;77,2%), other n=13; 2.5%) CT regimen choice was at physician’s discretion.. The main analysis is PFS as well as analysis of prognostic factors of this PFS (29 items including age (< 65 years n=229; 65-74 years n= 165.; ≥75years n=93). Univariate analysis was performed for each covariate, PFS was estimated by Kaplan-Meier curves and compared by log-rank test. univariable Cox regression analysis was used to assess the association between each variable and outcome. Multivariable stepwise Cox models were then fitted for final variable selection of prognostic factors on PFS. Results: Univariate significant prognostic factors for PFS are OMS (0-1 vs 2-3), Tobacco, Site of tumor (right vs other), Number of metastatic organ (1 vs 2-3), Resecability of metastatic disease defined before CT (definitively non resectable metastases vs possible resectable), Surgery of mCRC, folliculitis or xerosis or paronychia grade 0-1 vs 2-4. Age was unidentified as a prognostic factor in univariate analysis. Four factors were independently associated with a better PFS: xerosis [hazard ratio (HR0,651); 95% confidence interval (CI) 0,494-0,857], (WHO PS) 0–1 (HR0,519 ; 95% CI 0,371–0,726) and folliculitis (HR 0,711; 95% CI0,558–0,956) metastases surgery 0,287(CI 0,205-0,403). Conclusions: CTX in combination with standard CT is effective, age is not identified as a prognostic factor for the PFS. Both groups of pts based on age benefit from CTX.

First-Line Treatment with Rituximab Improves Survival of Patients with Post-Transplant Lymphoproliferative Disease (PTLD).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1406-1406 ◽  
Author(s):  
E. Gonzalez-Barca ◽  
E. Domingo-Domenech ◽  
J. Gomez-Codina ◽  
F. Capote ◽  
E. Flores ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Causes Of Death ◽  
Cox Regression ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Response To Treatment ◽  
Rank Test ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Disseminated Disease

Abstract Purpose: to compare the response rate and survival between patients diagnosed of PTLD and treated with front-line rituximab and those not treated with rituximab. Patients and Methods: 108 patients with PTLD have been studied from January 1996 to January 2004. Survival curves were expressed as Kaplan-Meier plots and were compared by the Log-rank test. A multivariate Cox regression analysis was performed to asses the effect of prognostic factors on survival. Results: median age was 55 years (limits: 18–73). 70% were males. The transplanted organ was: kidney 46%, liver 28%, heart 16%. Median time between transplant and PTLD was 59 months, 25% were diagnosed during the first year after the transplant. The most frequent histological subtypes were: large B-cell lymphoma 53% and polymorphic SLPT 13%. 70% were EBV +. Clinical characteristics at diagnosis were: disseminated disease: 52%, extra-nodal disease: 81%, ECOG 3 2: 43%, LDH &gt;N: 60%, IPI 3 3: 40%. Treatments used were: reduction of immunosuppression 91%, chemotherapy 59%, rituximab 33%, antiviral 13%. Response to treatment was: CR 46%, PR 13% failure 11%, not evaluable (early deceased): 29%. With a median follow-up of 15,2 months, survival was: OS 21% and EFS 15%. Forty-six (43%) patients died. The causes of death were: lymphoma progression 15 (33%), infection 15 (33%), toxicity 16 (34%). Survival of patients treated with rituximab was significantly better than the general group: OS 76% (p=0.007) and EFS 70% (p=0.02). Among patients treated with rituximab, 8 (23%) patients died. The significant bad prognostic factors for EFS in the multivariate analysis were: disseminated disease (RR: 2, 95% IC:1,02–3,8; p=0,04), ECOG 3 2 (RR: 5, 95% IC:2,6–9,8; p=0,0001), not been treated with rituximab (RR: 3,8, 95% IC: 1,7–10; p=0,001). IPI did not have prognostic impact. Conclusions: survival of patients with PTLD is low with conventional therapy, and the main causes of death are toxicity and infections. Treatment with Rituximab significantly improves their survival. Patients with disseminated disease and bad performance status have worse prognosis. IPI is not a useful index of prognosis in patients with PTLD.

Secondary Monoclonal Gammopathy Of Undetermined Significance Is Frequently Associated With High Response Rate and Superior Survival In Patients With Plasma Cell Dyscrasias

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5537-5537
Author(s):  
Dehui Zou ◽  
Gang An ◽  
Guoqing Zhu ◽  
Yan Xu ◽  
Weiwei Sui ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Clinical Parameters ◽  
Number Of Patients ◽  
Immunofixation Electrophoresis ◽  
Plasma Cell Dyscrasias ◽  
Undetermined Significance

Abstract Background Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon during the treatment of multiple myeloma (MM). The incidence, biological characteristics and prognostic value of secondary MGUS in patients with MM remain undefined. Materials and Methods Serum immunofixation electrophoresis (IFE) was retrospectively analyzed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia (pPCL). Patients who developed a secondary MGUS were identified through a retrospective analysis of serum immunofixation electrophoresis (IFE). IFE test was performed with Sebia Hydragel kits on the Sebia Hydrasys electrophoresis system (Sebia, Norcross, GA) using agarose gels. The identification of secondary MGUS required the detection of at least one new monoclonal (M) protein with heavy and/or light chain immunoglobulin different from the initially diagnosed MM Results Secondary MGUS was more common in patients with myeloma who had undergone SCT than in those who had not (17 [29.8%] out of 57 versus 5 [1.4%] out of 352, P < 0.001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The overall CR rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (p<0.01). The median PFS and OS of the entire cohort with MM was 25.0 months (95% CI: 19.9-30.0) and 36.0 months (95% CI: 29.4-42.6), respectively. Despite the small number of patients with secondary MGUS, these patients had a clearly better disease outcome as compared with those without secondary MGUS. The median PFS was 52.0 months (95% CI: 41.1-62.9) in patients with secondary MGUS versus 22.5 months (95% CI: 19.6-25.4) for the rest of the cohort (P = 0.002). Patients with secondary MGUS also had much longer OS, and the median OS was not reached versus 35.0 months (95% CI: 29.4-40.6) for the patients without secondary MGUS (P < 0.001). Univariate analysis performed on the whole group of 409 patients identified several prognostic factors that had significant negative effect on OS. These factors included advanced International Staging System stage (P<0.001), 17p deletion (P<0.001), 13q deletion (P=0.009), t(4;14) (P=0.042), 1q gains(P=0.006), absence of secondary MGUS (P<0.001). A multivariate Cox regression model including ISS stage, chromosome aberration determined by FISH and secondary MGUS was applied. The presence of secondary MGUS retained independent prognostic values for OS (HR 0.128 [95% CI 0.018-0.922], p=0.041). A similar analysis for prediction of PFS did not identify presence of sMGUS as independent prognostic factor. Survival was then analyzed in patients undergoing stem cell transplantation. Patients with secondary MGUS seemed to have a longer median PFS, but the difference was not statistically significant (52 months versus 41.0 months; p=0.126). Median OS was not reached in both group and no statistical difference was found (p=0.220) Conclusion We observe that secondary MGUS is frequently observed in MM patients after transplantation, and associated with a more favorable prognosis. The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS are comparable. The favorable survival could be explained by the higher depth of response especially after myeloablative therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

2009 ◽  
Vol 16 (2) ◽  
pp. 443-453 ◽  
Author(s):  
Marina Bagnoli ◽  
Federico Ambrogi ◽  
Silvana Pilotti ◽  
Paola Alberti ◽  
Antonino Ditto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Adverse Outcome ◽  
Multiple Correspondence Analysis ◽  
Nuclear Accumulation ◽  
Rank Test ◽  
Prognostic Impact ◽  
Apoptosis Resistance ◽  
Prognostic Information

The impairment of apoptotic pathways represents an efficient mechanism to promote chemoresistance in cancer cells. We previously showed that in epithelial ovarian cancer (EOC) cells, long isoform of cellular FLICE-inhibitory protein (c-FLIPL) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIPL downmodulation. Here, we studied the association between c-FLIPL and p53 expressions and their prognostic impact in EOC patients. Tumor tissue from 207 patients diagnosed with primary EOC was analyzed by immunohistochemistry (IHC) for c-FLIPL and p53 expressions, and multiple correspondence analysis (MCA) was used to evaluate the multivariable pattern of association among patients' clinical–pathological characteristics and biological determinants. IHC revealed c-FLIPL expression and p53 nuclear accumulation inversely related (P=0.0001; odds ratio=0.29, confidence interval (CI)=0.15–0.055). MCA indicated that p53 accumulation was associated to clinical–pathological variables, while c-FLIPL expression contributed to the overall association pattern independently from other's clinical characteristics and complementary to p53. Kaplan–Meier curves showed a reduced survival time according to c-FLIPL expression in concert with p53 accumulation (median overall survival (OS): 35 months) compared with lack of expression of both markers (median OS: 110 months; log-rank test, P value=0.024). The multivariable Cox regression model, adjusted for known prognostic factors, identified c-FLIPL expression, but not p53 nuclear accumulation, as an independent prognostic factor for adverse outcome (hazard ratio=1.82, 95% CI=1.17–2.82; P=0.008). Altogether these data support the independent contribution of c-FLIPL in refining the prognostic information obtained from standard clinical–pathological indicators, confirming its pivotal role in promoting cell survival.

scholarly journals Prognostic Impact of Hyperdiploidy on Multiple Myeloma in the Era of New Agents

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Yi Wang ◽  
Jing Zhuang ◽  
Gang An ◽  
Xue-Han Mao ◽  
Chenxing Du ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Prognostic Factor ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Univariate Analysis ◽  
Medical Science ◽  
Novel Agents ◽  
Prognostic Impact ◽  
Complex Karyotype

Introduction Multiple myeloma (MM) is a kind of hematological malignancy which is characterized by high genetic heterogeneity. It has been proved that the existence and even the coexistence of numerical and structural cytogenetic abnormalities (CAs) play a critical role in the development and progression of MM. Hyperdiploidy (HD), as one of the two primary CAs of MM, can be observed in around half of the patients and is considered as a favorable prognostic factor. Nevertheless, its role in overcoming the negative effect of concomitant high-risk CAs remains controversial. Although the outbreak of novel drugs by the last decades, such as proteasome inhibitors (PIs) and Immunomodulatory drugs (IMiDs), has significantly improved the survival of patients, MM is still incurable and can relapse recurrently. The prognostic impact of HD in the era of novel agents and its impact on other CAs are unclear and under to be explored. Here, we report our results based on the Chinese population to provide some evidence for the above questions. Methods A total of 213 patients between January 2013 to November 2017 were included in this study. All of the participants were from our database consisting of patients with newly diagnosed MM (NDMM) enrolled into the prospective, nonrandomized clinical trial (BDH 2008/02 or BDH 2014/03, all informed consents were obtained) approved by Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College. According to patients' willingness and specific conditions, they were assigned to either PI- or IMiD-based inductive treatment and maintenance, with or without autologous stem cell transplantation (ASCT) as consolidation therapy. Bone marrow aspirate samples were collected before the initiation of therapy and MM cells were enriched by CD138 magnetic beads. Then fluorescence in situ hybridization (FISH) was performed. Specifically, if patients possessed at least an extra copy of probes for any two of chromosomes 5, 9, or 15 concurrently in more than 10% cells, they would be classified into HD subgroup; otherwise, they would be divided into NHD (non-hyperdiploidy) subgroup. Clinical and biological baseline characteristics were compared. Progression-free survival (PFS) and overall survival (OS) were measured using the log-rank test. Significant variables from the univariate analysis were selected for the cox stepwise regression analysis. Results In our cohort, HD was identified in 34% (72/213) NDMM patients. HD was more common among older people (p=0.007). Patients with HD often had a lower level of serum albumin (p=0.037), but NHD patients had a higher frequency of elevated lactate dehydrogenase (LDH). Moreover, immunoglobulin isotype distribution was not similarly (p&lt;0.001), in which patients with NHD were more often IgD or light chain isotype. As to the genetics aspect, 99.1% (211/213) patients harbored at least one CA, and NHD patients appeared to be more genetic instability. 14q32 (IGH) translocation(p&lt;0.001), del(13q) (p&lt;0.001) and del(17p) (p=0.012) were likely to be detected in patients with NHD. However, there were no significant differences in the ratio of 1q21 gain/amplification and complex karyotype. Among patients with IGH translocation, t(14;undefined) [could not find partner genes by t(4;14), t(11;14), t(14;16) or t(14;20) probes] and t(11;14) were the most common translocation type in HD and NHD patients respectively. Median follow-up was 37 (4-82) months, Patients with HD showed a better median PFS (41 months vs. 27 months, p=0.047) and median OS (75 months vs. 55 months, p=0.024). Further subgroup analysis showed that the prolonged survival of HD was significant in patients who did not receive ASCT as part of the first-line therapy, but it could not overcome negative prognostic effects of other CAs except complex karyotype. Multivariate analysis confirmed that the state of ploidy was an independent prognostic factor for MM. Conclusions HD patients have specific differences in clinical and biological features. In the era of novel agents, MM patients with HD still have better survival than NHD. However, it may not ameliorate the adverse prognosis of concurrent high-risk CAs identified by FISH. Figure 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.

ID1 Expression Correlates with CEBPA Mutational Status and Is Not An Independent Risk Factor in Cytogenetically Normal AML,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3554-3554
Author(s):  
Katharina Wagner ◽  
Frederik Damm ◽  
Michael A Morgan ◽  
Felicitas Thol ◽  
Haiyang Yun ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
High Expression ◽  
Prognostic Impact ◽  
Mutational Status ◽  
Negative Prognostic Factor ◽  
Cebpa Mutations

Abstract Abstract 3554 Background: Acute myeloid leukemia with normal karyotype (CN-AML) is a heterogenous disease. During the last years, mutations in several genes (e.g. NPM1, FLT3, CEBPA, WT1, IDH1, IDH2) have been identified which are involved in the pathogenesis of AML and affect the prognosis of these patients. Moreover, deregulated expression of genes such as MN1, BAALC, ERG and WT1 was demonstrated to be predictive of outcome in CN-AML. Recently, high expression of the ID1 gene was described as a negative prognostic factor in AML (Tang et al. Blood 2009, 114:2993–3000). Aims: We have shown that C/EBPα, a transcription factor encoded by the CEBPA gene, binds to a regulatory element in the promoter region of the ID1 gene and regulates ID1 expression in leukemic cells (Wagner et al. Proc Natl Acad Sci USA 2006, 103:6338–6343). Therefore, we wanted to analyze the prognostic impact of ID1 expression in CN-AML in the context of other molecular markers, in particular CEBPA mutations. Methods: ID1 expression was quantified normalized to ABL by real time RT-PCR in 269 patients (age 16–60 years) with CN-AML treated with intensive double induction and consolidation therapy within the AMLSG 295 and 0199 trials (NCT00209833). The patients were also analyzed for mutations in the genes NPM1, FLT3, CEBPA, WT1, IDH1 and IDH2. Median follow up was 79 months. Results: Expression of ID1 varied over a 3-log range. High expression of ID1 (ID1high, defined as > median expression level) was significantly associated with the presence of a FLT3 -ITD or an IDH2 mutation and WT1 wildtype. Moreover, ID1 expression was closely associated with CEBPA mutational status. Altogether, 41 patients (15%) harboured a CEBPA mutation (24 monoallelic and 17 biallelic mutations). ID1 expression in the CEBPA wildtype patients was significantly higher than in patients with monoallelic CEBPA mutations and these patients had a significantly higher ID1 expression compared to patients with biallelic CEBPA mutations (p = 0.001). ID1high patients had a trend to a lower complete remission (CR) rate (74% vs. 84%; p = 0.07), but in multivariate analysis only blast clearance on day 15 after induction 1, age and WT1 SNP rs16754 were independent predictors for the achievement of CR. In univariate analysis, ID1high patients had an inferior overall survival (OS) compared to patients with low expression (median OS 29 vs. 78 months, 5 year OS 39% vs. 53%, p = 0.026). ID1high status was an independent negative prognostic factor in multivariate analysis when analyzed together with NPM1, FLT3 -ITD, WT1, IDH1, IDH2, extramedullary disease and platelet counts (HR 1.51; 95% CI 1.06–2.19). However, when also CEBPA mutational status was entered into the model, ID1 expression lost its prognostic impact and the only independent prognostic factors were age, platelets, CEBPA mutations, NPM1 /FLT3 -ITD risk group and WT1 SNP rs16754. Likewise, ID1high patients had a trend to an inferior relapse-free survival (RFS; HR 1.36, 95% CI 0.96–1.93, p = 0.086) in univariate analysis. However, in multivariate analysis including CEBPA mutational status, ID1 expression had no impact on RFS and the only prognostic factors for RFS were NPM1 and CEBPA mutations and WT1 SNP rs16754. In CEBPA wildtype patients, ID1 expression had no impact on CR-rate, OS or RFS in univariate or multivariate analysis. Conclusions: CEBPA mutations seem to deregulate ID1 expression in CN-AML. Therefore, ID1 expression is not an independent prognostic factor in CN-AML. Disclosures: No relevant conflicts of interest to declare.

Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients

2021 ◽  
pp. 000313482110415
Author(s):  
Naruhiko Honmyo ◽  
Tsuyoshi Kobayashi ◽  
Shintaro Kuroda ◽  
Kentaro Ide ◽  
Masahiro Ohira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Portal Hypertension ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Hemoglobin Level ◽  
Rank Test ◽  
Predictive Index ◽  
Preoperative Hemoglobin ◽  
Preoperative Hemoglobin Level

Background Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. Methods This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. Results Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( P < .001), and preoperative hemoglobin level ( P = .007) were related to HCC development, and the presence of HCC history ( P = .002) and preoperative hemoglobin level ( P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). Discussion The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

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