Serum Peptidome Based Multiple Myeloma Renal Impairment Biomarker Screening

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2968-2968
Author(s):  
Ju Bai ◽  
Aili He ◽  
Wanggang Zhang ◽  
Yun Yang ◽  
Jianli Wang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Overall Survival ◽  
Correlation Analysis ◽  
Renal Impairment ◽  
Relative Intensity ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Tubular Injury ◽  
Kaplan Meier ◽  
Renal Tubular

Abstract Background: Renal impairment (RI) is relatively common in patients with newly diagnosed MM (NDMM), ~20-40%, and forms one of the defining features for diagnosis of symptomatic disease. RI has a negative prognostic impact in patients with MM, with an increased risk of early death and a reduction in median survival of up to 50% compared with MM patients without RI. Identification of the early RI in MM and prompt intervention can effectively reverse the RI and prolong the survival of patients. Considering serum creatinine (SCr), blood urea nitrogen (BUN) and creatinine clearance (CrCl) are difficult to reflect early RI, cystatin C (Cys-C), as a new biomarker, has certain value for the diagnosis of early glomerular impairment in MM. However, the early stage of RI in MM was mainly renal tubular injury. Low molecular urine protein (retinol-binding protein, β-microglobulin) are effective in early renal tubular injury, but they are affected by urea PH value. This study was to screen a panel of serum peptides associated with early RI in MM. Methods: 164 MM patients were selected from those who were newly diagnosed in the Second Affiliated Hospital of Xi'an Jiao Tong University during a given period of time (2009.1-2014.1). Their diagnoses were made according to the diagnostic criteria from the International Myeloma Working Group. The median age was 65 years old (range 36-83) and 60.4% were male. RI was defined as having a CrCl<40ml/min. Weak cation exchange magnetic bead combined with matrix assisted laser desorption/ionization time of flight mass spectrometry were used to compare and analyze serum peptidome of MM with or without RI. Correlation analysis of two variables was estimated by Spearman method. The patients were categorized into two groups according to the relative intensities of peptides (≥mean versus <mean). Overall Survival was estimated by the Kaplan-Meier method and compared using a log-rank test. The event was defined as the time from initial diagnosis to treatment-related death time. Statistical significance was defined as p<0.05. Results: Serum peptidome of MM including 104 without RI and 50 with RI were analysed. 18 statistically different expressed peptide peaks were obtained in the molecular weight range of 700-10000Da (P<0.05), among which, 7 peptides were upregulated and 11 peptides were downregulated. Quick classifier (QC) model had optimal distinction efficiency, in the training set with a sensitivity of 93.33% and a specificity of 90%. Blind test verified that this model correctly identified 18 cases out of total 20 MM with RI and 70 cases from 74 MM without RI. Peptides with molecular weight of 3908.85Da and 3216.06Da were significant upregulated in MM patients with RI. Relative intensities of the two peptides were decreased when CrCl(38/50MM) was improved to 40ml/min after therapy. Peptide with molecular weight of 2990.08Da was significant downregulated in MM patients with RI. Its relative intensity was elevated after therapy(CrCl>40ml/min,38/50MM). Spearman correlation analysis showed that relative intensities of peptides with molecular weight of 3908.85Da, 3216.06Da and 2990.08Da were correlated with SCr(r=0.81, p<0.001; r=0.84, p<0.001; p=-0.86, p<0.001), CrCl(r=-0.79, p<0.001; r=-0.81, p<0.001; r=0.83, p<0.001), BUN(r=0.74, p<0.001; r=0.77, p<0.001; r=-0.79, p<0.001), Cys-C(r=0.81, p<0.001; r=0.84, p<0.001; r=-0.86, p<0.001). The median follow-up duration among 164 patients was 27 months (range 4-52 months). Kaplan-Meier analyses of overall survival (OS) showed that patients with higher relative intensities of peptide with 3908.85Da and 3216.06Da (≥mean relative intensity) had a significantly inferior outcome. Lower relative intensities of peptides with molecular weight of 3908.85Da and 3216.06Da (<mean relative intensity) was associated with a favorable OS (46.2±9.2% versus 16.1±6.5%, p=0.012; 41.7±9.5% versus 18.5±6.0%, P=0.021). The OS rate was higher in patients with increased relative intensity of peptides with molecular weight of 2990.08Da (≥mean relative intensity) of than in those with decreased relative intensity (<mean relative intensity)(36.1±10.5% versus 16.2±4.7%, p=0.008). Conclusion: Peptides(3908.85Da, 3216.06Da and 2990.08Da) associated with MM RI obtained by serum peptidome technology can provide new clue for early assess and diagnose MM RI in clinical. Disclosures No relevant conflicts of interest to declare.

Response and Overall Survival Is Impaired in Obese Patients with Acute Myelogenous Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1522-1522
Author(s):  
Martina Crysandt ◽  
Edgar Jost ◽  
Susanne Isfort ◽  
Tim H Brümmendorf ◽  
Stefan Wilop
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Induction Therapy ◽  
Risk Group ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Obese Patients ◽  
Newly Diagnosed ◽  
Laboratory Parameters

Abstract Abstract 1522 Introduction Dose calculation of chemotherapeutic agents is mainly based on body surface area (BSA). Historically, in many institutions, doses are not adapted to a BSA above 2 sqm, although recent data suggested that this relative dose reduction in patients above 2 sqm is associated with a worse outcome. Obesity is a widespread and increasing phenomenon in the developed countries and is mainly defined by the body mass index (BMI). It is known, that the risk to develop haematological or solid malignancies is increased in obese patients – and, additionally, weight influences outcome in several tumours. Therefore, in our study, we analyzed the prognostic impact of obesity in newly diagnosed AML regarding the response to the first cycle of induction therapy and overall survival. Methods We identified 145 patients with newly diagnosed AML who were treated with induction therapy containing cytarabine and an anthracycline in our institution. Clinical data including several laboratory parameters associated with nutritional status (cholesterol, triglycerides, protein, C-reactive protein, albumin, lymphocyte count, transferrin, pseudo-cholinesterase, fT3, b-type natriuretic peptide), long-term medication with statins, chemotherapy dosing as well as response and overall survival have been assessed retrospectively from the institution's database. In our institution, all patients with a high BSA received a chemotherapy-dose calculated with a cut-off of not more than 2 sqm. Results In our cohort, median BMI was 25.2 kg/sqm (range 17.0 – 48.1). Seventeen patients had a BMI above 31 kg/sqm, 128 below. The median BSA of all patients was 1.83 sqm (range 1.49 – 2.40). In 41 patients, chemotherapy doses have been adjusted owing to a BSA of more than 2 sqm. We included cytogenetic risk group, BMI, BSA above 2.0 sqm, weight, long-term medication with statins and laboratory parameters in our univariate and multivariate analysis. Only cytogenetic risk group (p=0.001), triglycerides (p=0.008) and the BMI (p=0.032) were independent risk factors for overall survival. Univariate analysis showed similar results. Patients with a BMI >31 showed a significantly worse response (PR + CR) on first induction therapy (47.1% vs. 74.8%, p=0.018) and a shorter median survival (11.2 vs. 25.1 months, p=0.004). Both BMI-groups showed the same distribution of well-known risk factors including age, cytogenetic risk groups and secondary AML. Discussion/Conclusion In our cohort, a high BMI was associated with poorer response and impaired overall survival, whereas BSA was not. This leads to the conclusion, that the adverse effect may be mediated by obesity itself and not caused by underdosing of chemotherapy. Although an effect of BMI is known from several solid tumours, the reason remains unclear. Possible explanations include altered metabolisation and production of growth factors in adipose tissue (possibly indicated by elevated triglycerides), impaired or accelerated hepatic drug activation and/or metabolisation or impact on immune function. This study is limited by the retrospective single-center design and the relatively small patient number. Nevertheless, the data clearly confirmed other well established risk factors like the cytogenetic risk group supporting the validity of this approach. The study results suggest BMI as an independent risk factor for AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic Impact of Bone Marrow Erythropoiesis on Newly Diagnosed Plasma Cell Myeloma: A Single Institutional Analyses

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5579-5579
Author(s):  
Daniel E Ezekwudo ◽  
Rohit Singh ◽  
Bolanle Gbadamosi ◽  
Mark Micale ◽  
Ishmael Jaiyesimi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Outcome ◽  
Plasma Cell ◽  
Prognostic Impact ◽  
Plasma Cell Myeloma ◽  
Newly Diagnosed ◽  
Bone Marrow Biopsies ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Impact

Abstract Introduction: In plasma cell myeloma (PCM), tumor burden and activity plays an important role in diagnosis and prognosis (e.g. circulating plasma cells), however very little attention has been directed to the impact of the non-plasma cell component of the bone marrow. The presence of anemia has been used to distinguish PCM from smoldering myeloma; however this can be a non-specific finding as there are many potential causes of anemia besides PCM. We sought to determine if the level of erythropoiesis in bone marrow biopsies may be a more reliable prognostic factor. In the study herein, we assessed the level of bone marrow erythropoiesis in patients with newly diagnosed PCM, and compared those findings with cytogenetic results (CGs), other prognostic factors and overall clinical outcome. We hypothesized that patients with adequate erythropoiesis (AEp) are likely to have favorable cytogenetics and better outcome compared to those with decreased erythropoiesis (DEp). Methods: We retrospectively reviewed pathology database for bone marrow biopsies in patients with diagnosis of plasma cell myeloma (PCM) at Beaumont Hospital, an academic community center from 2012 and 2014. Biopsy cases without anemia were excluded. A total of 91 patients with plasma cell myeloma and anemia were identified. Each biopsy was re-examined to determine the level of erythropoiesis. The level of erythropoiesis was calculated by multiplying erythroid fraction (obtained from M:E ratio) with non-plasma cell bone marrow cellularity. Cases were separated into AEp and DEp using an erythroid compartment cut-off of 7.5% based on already established data. Kaplan-Meier analysis was used to compare survival between groups. Results: Demographic distribution of studied patients were 46 (50.1%) white, 39 (43%) African Americans and 6 (6.6%) others. Out of 91 cases analyzed, 38 (42%) had AEp whereas 53 (58%) had DEp. Among those with AEp, 23 (62%) had favorable CGs (defined as those without t (4, 14), t (14, 16), t (14, 20) or 17 p deletion); 15 (38%) had unfavorable CGs. Among those with DEp, 14 (26%) had favorable CGs whereas 39 (74%) had unfavorable cytogenetics. The vast majority of patients with favorable CGs were alive whether they had AEp (87%) or DEp (79%), thus CGs remained significant even after controlling for erythroid compartment (p = 0.03). Overall, those with AEp were noted to have significantly lower β-2 microglobulin (AEp median =2.42 mg/dL, DEp median = 4.50 mg/dL, p = 0.02). Kaplan-Meier analysis showed a significant difference in survival curves among the four groups (AEp with favorable CGs, AEp with unfavorable CGs, DEp with favorable CGs, DEp with unfavorable CGs, p<.0001). While the two groups with favorable CGs showed no significant difference (p=.6050), the two groups with unfavorable CGs did (p=.0027). Conclusion: Our findings suggest that patients with PCM and anemia are not a homogenous population. Assessment of the erythroid compartment in these patients reveals a population with AEp that has more favorable CGs and lower β-2 microglobulin than patients with DEp. Despite this finding, patients with favorable CGs had a favorable clinical outcome whether they had AEp or not, indicating that current therapies can overcome differences in erythropoiesis in that group. For patients with unfavorable CGs, however, those with AEp had superior survival outcome compared to those with DEp, indicating that there may be some prognostic or diagnostic utility to assessing erythropoiesis in patients who meet current criteria for PCM, and possibly, incorporating erythropoietic activity into diagnostic/prognostic schema. Disclosures No relevant conflicts of interest to declare.

scholarly journals Incidence of spinal disease and role of spinal radiotherapy in multiple myeloma

2018 ◽  
Vol 25 (6) ◽  
Author(s):  
A. M. Sharma ◽  
M. Sackett ◽  
D. Bueddefeld ◽  
P. Lambert ◽  
A. Dubey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Cord Compression ◽  
Newly Diagnosed ◽  
Spinal Disease ◽  
Kaplan Meier ◽  
Long Term Survivors

Background Spinal disease (spd) in multiple myeloma (mm) can be a major source of morbidity in newly diagnosed patients and long-term survivors. We retrospectively assessed the incidence of spinal disease in patients newly diagnosed with myeloma, its effect on survival, and the possible effect of spinal radiation therapy (rt).Methods Patients diagnosed with mm between 2010 and 2014 were identified through the provincial cancer registry. Plain radiography, computed tomography, and magnetic resonance imaging were reviewed to detect and document the type of spd. Data related to rt and systemic therapy were collected. Kaplan–Meier and time-varying Cox regression models were used to describe overall survival.Results Of 306 identified patients with newly diagnosed mm, 51% had spd, including 17% with lytic disease, 68% with compression fractures, and 15% with spinal cord compression. Of the patients with spd, 61% received spinal rt. Of those patients, 84% received spinal rt within 3 months after their diagnosis. Median dose was 20 Gy. Most patients (89.2%) received chemotherapy, and 22.5% underwent autologous stem-cell transplantation. Only 6 of the patients treated with spinal rt received re-irradiation to the same site. Overall survival was similar for patients with and without spd. On multivariate analysis, spinal rt had no effect on survival.Conclusions In patients newly diagnosed with mm, spd is a common presentation. With current systemic therapy, the presence of spd had no adverse effect on overall survival. The effect of spinal rt on overall survival was nonsignificant.

Albumin Is a Prognostic Factor for Overall Survival in Newly Diagnosed Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4253-4253
Author(s):  
Awais M. Khan ◽  
Jeffrey E. Lancet ◽  
Mohamed A. Kharfan-Dabaja ◽  
Najla H Al Ali ◽  
Alan F. List ◽  
...  
Keyword(s):  
Overall Survival ◽  
Serum Albumin ◽  
Induction Chemotherapy ◽  
Serum Albumin Level ◽  
Cox Regression ◽  
Albumin Level ◽  
Normal Serum ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
History Of

Abstract Abstract 4253 Background: Hypoalbuminemia (HA) is a strong predictor of poor clinical outcomes in many medical conditions. Low serum albumin is recognized as an adverse prognostic factor in patients with neoplastic diseases such as multiple myeloma, melanoma, and colon cancer. Severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic cell transplant (AHCT) was reported as an independent predictive variable for non-relapse mortality and overall survival (Kharfan-Dabaja, et al Biol Blood Marrow Transplant 2009; 15). A separate study conducted by our group showed that in patients with relapsed and refractory AML, serum albumin < 3.5 g/dl prior to salvage chemotherapy, correlated with lower complete remission (CR) rate and inferior overall survival (OS) (Komrokji, et al ASH 2009). We examined the prognostic value of serum albumin level prior to induction chemotherapy in patients with newly diagnosed AML. Methods: Data were collected retrospectively in a cohort of newly diagnosed AML patients who received induction chemotherapy (3+ 7 regimen). The primary objective of this study is to examine the relationship between serum albumin at baseline and probability for achieving complete remission (CR) or incomplete remission (CRi) and overall survival (OS). All analyses were conducted using SPSS version 19.0. The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups and Cox regression for multivariable analysis. Results: Between November 2004 and July 2007, 135 patients who received 3+7 induction chemotherapy at Moffitt Cancer Center were included in this analysis. Patient baseline characteristics were similar between patients with baseline serum albumin < 3.5 g/dl (HA) and those with serum albumin ≥ 3.5 g/dl (no HA) with respect to age, sex, FAB subtype, history of antecedent MDS, karyotype, and chemotherapy. Patients with HA, mean age was 60 years compared to 56.5 years in non HA group. The median OS for patients with HA was 221 days (95%CI 149.5–292.5) compared to 421 days (95%CI 236.7–605) with normal serum albumin (p<0.005). (Figure-1) The CR/CRi rate was 64%% for HA and 77.6% for those with normal albumin (p=0.09). In a multivariable Cox regression analysis including age ≥ 60 years, history of MDS, karyotype, and serum albumin level at baseline; only age, karyotype and serum albumin were independent predictors of OS [Hazard ratio 0.47 (95%CI 0.31–0.71) (p<0.005) for normal serum albumin group]. Conclusion: In this cohort of patients with newly diagnosed AML, we demonstrate that hypoalbuminemia < 3.5 g/dl is an independent covariate for overall survival with conventional chemotherapy management. Serum albumin is a surrogate marker of general health, comorbidities, and performance status. The prognostic value of low serum albumin should be validated in a prospective study. Disclosures: No relevant conflicts of interest to declare.

Effectiveness of a Strategy to Proceed to Allogeneic Stem Cell Transplantation in All Elderly AML Patients Treated with Intensive Chemotherapy: Only Patients in Complete Remission After First Induction Show Long Term Survival.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3085-3085
Author(s):  
Peter A. Von Dem Borne ◽  
Constantijn J.M. Halkes ◽  
Erik W.A. Marijt ◽  
Sabina Kersting ◽  
J.H. Frederik Falkenburg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Consolidation Chemotherapy ◽  
Early Relapse ◽  
Kaplan Meier ◽  
Elderly Aml ◽  
Treat Population

Abstract Abstract 3085 Introduction Acute myeloid leukemia (AML) in patients over 60 years has a poor prognosis with 2-year survival rates of less than 10%. Intensive chemotherapy improves interim survival but not long term cure rates compared to non-intensive care. Allogeneic stem cell transplantation (alloSCT) has the potential to cure elderly AML patients, but most reported studies refer to selected patient cohorts. We have developed a T cell-depleted reduced intensity conditioning (RIC) regimen and preplanned post alloSCT donor T-cell infusion, inducing only limited GVHD directly after alloSCT (von dem Borne et al. Curr Opin Oncol 2009) making it a suitable regimen for elderly patients. In 2006, we instituted a center policy to perform RIC alloSCT in every newly diagnosed AML and high grade MDS patient >60 years who qualified for induction therapy. We here report feasibility, toxicity, and outcomes of this strategy. Patients and methods From 2006 to 2011, 45 consecutive patients aged 60–79 years (median: 67) with newly diagnosed AML (n=43) or high-risk MDS (IPSS score >1.5) started induction chemotherapy (continuous infusional cytarabine combined with bolus anthracycline with or without etoposide). Patient not achieving complete remission (CR) after induction received a re-induction cycle with high-dose cytarabine with or without amsacrine. Patients in CR after induction or re-induction were to receive one cycle of consolidation chemotherapy, followed by RIC alloSCT in case of continuous CR. Results Six patients (13%) died during first induction. 19 patients (43%) achieved CR after first induction, of which 12 received a RIC alloSCT (27% of intention-to-treat population) after consolidation chemotherapy. Causes why CR patients did not receive alloSCT were good-risk AML (n=1), early relapse after consolidation chemotherapy (n=2), high age (patient had become over 80 years) (n=1), infectious complication (n=1) and patient choice (n=2). 20 patients (45%) failed to achieve a CR after induction chemotherapy. 16 of these patients received the planned re-induction therapy; 10 of these patients achieved a CR, 7 patients received a third chemotherapy course for consolidation, and 4 underwent RIC alloSCT. There were no long-term survivors in this group. 19 patients without CR after 1st induction died from progressive AML.15 AML deaths after 1st induction failure occurred in patients who were treated according to the institutional strategy (6 patients with progressive disease despite additional chemotherapy, 1 relapse prior to start of re-induction, 3 relapses early after consolidation, and 4 relapses after alloSCT). Relapses in patients not adhering to the pre-specified strategy occurred in patients opting to discontinue therapy while in CR (n=3), inability to find a donor (n=1), and complication preventing alloSCT (n=1). One transplanted patient died from GVHD. For the entire intent-to-treat population, the Kaplan-Meier estimate for overall survival at 1 and 2 years after start of treatment is 38% and 19%, respectively. For patients achieving CR after 1st induction and receiving alloSCT, Kaplan-Meier estimate overall survival at 2 years after start of treatment is 50%. The main reasons for dying when adhering to the protocol were early death (13%) and refractory/relapsing malignancy (47%). Only 2 patients (4%) died after 1st induction as a consequence of TRM. Non-TRM reasons for not adhering to the protocol with subsequent death due to AML were patient preference (n=4; 9%) and inability to identify a matched donor (n=1; 2%). Conclusions This single-center comprehensive cohort study shows that 38% of elderly AML patients that are deemed fit for induction chemotherapy can be brought to alloSCT in CR. At diagnosis, this strategy offers a chance of cure for about 20% of patients. Fifty percent of patients achieving CR after 1st induction and receiving alloSCT are alive 2 years after alloSCT. Since none of the patients who failed to achieve a CR after 1st induction survived long-term, the most important aspect to improve this strategy is to strive for higher primary CR rates, including the prevention of early deaths. Alternative strategies, such as combining alloSCT and consolidation chemotherapy into one coherent regimen may especially improve outcome by preventing early relapse and improving patient compliance. Post-induction TRM and lack of a donor were only minor obstacles to this potentially curative approach. Disclosures: No relevant conflicts of interest to declare.

Increased Circulating Plasma Cells Predicts Poor Overall Survival in Symptomatic Plasma Cell Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4205-4205
Author(s):  
Mi Hyun Bae ◽  
Sang Hyuk Park ◽  
Chan-Jeoung Park ◽  
Bo Hyun Kim ◽  
Young-Uk Cho ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Survival Curve ◽  
Plasma Cell Myeloma ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
Meier Survival Curve

Abstract Backgrounds Flow cytometry can rapidly determine immunophenotypes of neoplastic plasma cells (PCs) and quantify PCs in patients with plasma cell myeloma. Flow cytometric immunophenotyping and quantification of neoplastic plasma cells is sensitive and reliable tool for diagnosis and disease monitoring in patients with monoclonal gammopathy. Circulating PCs (cPCs) in peripheral blood (PB) after autologous hematopoietic stem cell transplantation is a marker of high-risk disease in patients with plasma cell myeloma. We assessed the utility of quantification of cPCs using flow cytometry for risk stratification in newly diagnosed plasma cell myeloma patients in the era of novel agents. Methods PB and bone marrow (BM) aspirates of 85 newly diagnosed patients with symptomatic plasma cell myeloma from August 2013 to July 2014 were analyzed by five-color flow cytometry using monoclonal antibodies against CD45, CD19, CD56, CD38, and CD138. The gating strategy employed first used the expression of CD38 and CD138 to identify plasma cells among 100,000 to 200,000 events. cPCs in PB was determined according to the patient's specific immunophenotype of neoplastic PCs in BM. Results The median age of the patient population was 68 years (45~87) and 58% were female. Median follow-up duration was 19.2 months. Six out of 85 patients (7%) did not show cPCs. Among 79 patient (93%) who had detectable cPCs, the median cPCs was 0.09% (0.006~3.612%). Patients without cPCs or cPCs under 0.05% were assigned to low cPCs group (n=32, 38%) and others to high cPCs group (n=53, 62%) according to receiver operating characteristics analysis. High cPCs group showed higher level of BM neoplastic PCs detected by both methodologys of morphology and flow cytometry (P=0.002, 0.033, respectively), higher BM cellularity (P=0.011), higher serum M protein level (P=0.013), lower hemoglobin (P=0.008), and lower platelet level (P=0.034) than low cPCs group. High cPCs group was associated with adverse cytogenetics such as t(4;14) and monosomy 13 (P=0.008), and CD45 negative immunophenotype (P=0.007). In survival analysis, high cPCs presented shorter overall survival (OS) than low cPCs group (P=0.013) (Fig. 1). It was independent with patient age and cytogenetic risks (P =0.011). Conclusion By flow cytometry cPCs was detected in most symptomatic plasma cell myeloma patients. Increased cPCs ≥0.05% among PB leukocytes could be an independent prognostic factor showing adverse effect in overall survival in symptomatic plasma cell myeloma patients. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Disclosures No relevant conflicts of interest to declare.

scholarly journals Expression of Myeloid Antigen in Neoplastic Plasma Cells Is Related to Adverse Prognosis in Patients with Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hyoeun Shim ◽  
Joo Hee Ha ◽  
Hyewon Lee ◽  
Ji Yeon Sohn ◽  
Hyun Ju Kim ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Bone Marrow Histology ◽  
Myeloid Antigens ◽  
Kaplan Meier ◽  
Patient Prognosis ◽  
Expression Status

We evaluated the association between the expression of myeloid antigens on neoplastic plasma cells and patient prognosis. The expression status of CD13, CD19, CD20, CD33, CD38, CD56, and CD117 was analyzed on myeloma cells from 55 newly diagnosed patients, including 36 men (65%), of median age 61 years (range: 38–78). Analyzed clinical characteristics and laboratory parameters were as follows: serumβ2-microglobulin, lactate dehydrogenase, calcium, albumin, hemoglobin, serum creatinine concentrations, bone marrow histology, and cytogenetic findings. CD13+ and CD33+ were detected in 53% and 18%, respectively. Serum calcium (P=0.049) and LDH (P=0.018) concentrations were significantly higher and morphologic subtype of immature or plasmablastic was more frequent in CD33+ than in CD33− patients (P=0.022). CD33 and CD13 expression demonstrate a potential prognostic impact and were associated with lower overall survival (OS;P=0.001andP=0.025) in Kaplan-Meier analysis. Multivariate analysis showed that CD33 was independently prognostic of shorter progression free survival (PFS;P=0.037) and OS (P=0.001) with correction of clinical prognostic factors. This study showed that CD13 and CD33 expression associated with poor prognosis in patients with MM implicating the need of analysis of these markers in MM diagnosis.

scholarly journals What Effect Do Pulmonary Micronodules Detected at Presentation in Patients with Osteosarcoma Have on 5-Year Overall Survival?

2021 ◽  
Vol 10 (6) ◽  
pp. 1213
Author(s):  
Reid Davison ◽  
Fadi Hamati ◽  
Paul Kent
Keyword(s):  
Computed Tomography ◽  
Overall Survival ◽  
Surgical Intervention ◽  
Survival Rates ◽  
Pulmonary Nodules ◽  
Survival Advantage ◽  
University Hospital ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
Overall Survival Rates

For osteosarcoma, staging criteria, prognosis estimates, and surgical recommendations have not yet changed to reflect increasingly sensitive computed tomography (CT) imaging. However, the frequent identification of micronodules (<5 mm) on presentation leaves clinicians in a difficult position regarding the need to biopsy, resect, or follow the lesions and whether to consider the patient metastatic or non-metastatic. Our objective was to compare the 5-year overall survival rates of patients with osteosarcoma with non-surgically resected lung micronodules on presentation to patients without micronodules to guide community oncologists faced with this common dilemma. We collected data retrospectively on all newly diagnosed osteosarcoma patients, aged less than 50, treated at Rush University Hospital over 25 years without pulmonary nodules >10 mm or pulmonary surgical intervention. Kaplan–Meier curves showed there was no difference in 5-year overall survival in patients with any size nodule <5 mm compared to patients with no nodules. Additionally, our study showed a survival advantage for those who presented with 0 or 1 nodule (90%) compared to ≥2 nodules (53%). Our data suggest surgery may not be necessary for singular nodules <5 mm identified on presentation, and that these patients behave more like “localized” patients than metastatic patients.

scholarly journals Bone Marrow Mastocytosis Is Independently Associated with Inferior Survival in Chronic Myelomonocytic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2956-2956
Author(s):  
Andrew T Kuykendall ◽  
Anthony Hunter ◽  
Ling Zhang ◽  
Eric Padron ◽  
Chetasi Talati ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Prognostic Model ◽  
Systemic Mastocytosis ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Kaplan Meier ◽  
Myelomonocytic Leukemia ◽  
Baseline Demographic

Introduction: Systemic mastocytosis with associated hematologic neoplasm (SM-AHN) is defined by the presence of a concomitant hematologic malignancy with chronic myelomonocytic leukemia (CMML) being a particularly common partner. The overall survival of patients with SM-AHN is inferior to those with SM alone, even when matched for relevant prognostic covariates. However, the prognostic impact of mastocytosis in patients with CMML is unknown. Methods: CMML patients with concomitant mastocytosis were identified from the Moffitt Cancer Center CMML database. We assessed baseline demographic, clinical, and molecular findings and used Kaplan-Meier method to estimate overall survival (OS). The log-rank test was used to compare Kaplan-Meier curves, We then compared the SM-CMML cohort to a well-established institutional database of CMML patients. Baseline demographic and clinical variables were analyzed using GraphPad Prism and SPSS was used for Cox Regression Analysis. Results: Between 5/2004 and 5/2019 22 of 645 CMML patients (3.4%) were identified to have concomitant mastocytosis. The median follow-up for the 22 patients with SM-CMML was 51 months. Nine (41%) patients were diagnosed with de novo CMML prior to SM. In these cases, secondary SM-CMML occurred at a median time of 7 months after CMML diagnosis. Ten patients (45%) were diagnosed with CMML and SM concurrently and 3 (14%) were diagnosed with SM prior to CMML. Among 17 patients tested for KIT mutations, 12 were found to harbor a mutation. The remaining five patients did not undergo high-sensitivity KIT testing on a bone marrow aspirate. Eleven patients had extended gene sequencing performed with the most common additional mutations involving TET2 (45%), SRSF2 (55%), ASXL1 (27%), RAS (27%), DNMT3A (27%), and RUNX1 (27%). The median overall survival (OS) was estimated to be 38.6 months. Next, we compared this cohort of SM-CMML patients to a large, established database of CMML patients (excluding those with concomitant SM). Age at diagnosis, baseline white blood cell count, hemoglobin, and platelet count were well matched between the two groups. Applying the Mayo CMML Prognostic Model to the cohort of SM-CMML patients demonstrated that 32%, 41%, and 27% were low, intermediate and high risk, respectively. In the CMML cohort, 13%, 35%, and 51% were low, intermediate and high, risk respectively, suggesting the SM-CMML was more common in the lower-risk group (p=0.025). The median OS was similar between the two cohorts (median OS 31.3 vs 38.6 months, p = 0.43). However, multivariate analysis including Mayo Prognostic Scoring System, age > 65, and SM component revealed all three variables to be independently associated with survival (HR 1.8, p < 0.001; HR 1.7, p = 0.047; and HR 1.5, p 0.003, respectively). Assessing the impact of mastocytosis in low, intermediate, and high-risk groups separately, the inferior prognostic impact of mastocytosis was most prominent in high-risk patients (OS 19.6 mo vs. 5.4 mo; p = 0.049). Survival outcomes between SM-CMML and CMML were not statistically different in intermediate and low-risk groups (p = 0.47 and p = 0.19, respectively). Among 16 deaths in the SM-CMML cohort, cause of death was able to be assessed in 13 patients. Four (31%) patients died after transformation to acute myeloid leukemia (AML). These patients were either intermediate- or high-risk by Mayo Prognostic Model. Nine patients (69%) died due to multisystem organ failure due to progressive systemic mastocytosis without development of acute leukemia. Among these, 4 (44%) were low-risk, 3 (33%) were intermediate-risk, and 2 (22%) were high-risk. Conclusions: SM-CMML typically presented with lower-risk disease when graded by the Mayo CMML Prognostic Model. Compared head-to-head, OS was similar between SM-CMML and CMML; however multivariate analysis revealed the SM component to be a significant adverse prognostic factor. The presence of bone marrow mastocytosis is associated with inferior survival in high-risk CMML cases. Cause of death among SM-CMML patients was attributable to both progressive mastocytosis and transformation to AML. AML transformation was limited to intermediate- and high-risk group while progressive mastocytosis was seen across the risk spectrum. Future studies are warranted to determine if SM therapy can mitigate this outcome. Figure 1 Disclosures Kuykendall: Abbvie: Honoraria; Celgene: Honoraria; Incyte: Honoraria, Speakers Bureau; Janssen: Consultancy. Talati:Celgene: Honoraria; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria. Komrokji:DSI: Consultancy; Incyte: Consultancy; Agios: Consultancy; JAZZ: Consultancy; JAZZ: Speakers Bureau; Novartis: Speakers Bureau; pfizer: Consultancy; celgene: Consultancy.

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