Clinical Analysis of Thromboembolism Associated with Lenalidomide-Based Regimens for Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5368-5368
Author(s):  
Xiaoyan Qu ◽  
Yan Gu ◽  
Jianyong Li ◽  
Lijuan Chen
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Venous Catheter ◽  
Disease Status ◽  
Clinical Analysis ◽  
Filter Placement ◽  
Vein Thrombosis ◽  
Surgical History

Abstract Objective: To investigate and analyze the incidence, risk factors, prophylaxis and treatment of thromboembolism associated with lenalidomide-based regimens for multiple myeloma (MM) patients. Methods: 22 newly diagnosed / relapsed MM patients received lenalidomide-based regimes from May 2013 to May 2015 in our department. All diagnosis of thromboembolism were based on objective clinical symptoms, and confirmed by imaging (lower extremity vascular ultrasound, chest CT angiography (CTA), and two-dimensional echocardiography). Investigatethe incidence of thethromboembolism, and analyze the prophylaxis and treatment for the thromboembolism according to risk factors such as patients' characteristics, disease status, and therapy regimes. Results: Aspirin was used as thromboprophylaxis in 16 patients, low molecular weight heparin (LMWH) in 2 patients, and warfarin in 1 patient, while 3 patients received no thromboprophylaxis. There were 4 cases were diagnosedas thromboembolism with the incident of 18.2%. Threeof them were deep vein thrombosis (DVT), while 1 patient was combined withpulmonary embolism (PE), andthe rest one was found thromboembolism in the left atria. The chemotherapy regimes were lenalidomide plus dexamethasone (≤40mg qw). Other risk factors include: old age, male, immobility, central venous catheter (CVC), surgical history, hypertension, cardiovascularevent, IgG/IgA and light chain type, newly diagnosis, and erythropoietin (EPO). The management of thromboembolism included LMWH, warfarin, venous filter placement, adjustment of chemotherapy regimes and maintenance therapy of antithromboembolism. All the 4 patients were well managedat the last follow-up. Conclusion: Thromboembolism was one of the most common non-hematologic adverse events of lenalidomide-based therapy. Aspirin was an effective option for thromboprophylaxis. More cases will be observed for longer time to optimize further evaluations forantithromboticprophylaxes, which include risk stratification-based prophylacticstrategies, new predictors and specific assessment of all thromboprophylaxis options. Disclosures No relevant conflicts of interest to declare.

scholarly journals Correlation of clinical features with the risk of lower limb deep vein thrombosis assessed by duplex ultrasound

2013 ◽  
Vol 12 (2) ◽  
pp. 118-122
Author(s):  
Liz Andrea Villela Baroncini ◽  
Graciliano Jose Franca ◽  
Aguinaldo de Oliveira ◽  
Enrique AntonioVidal ◽  
Carlos Eduardo Del Valle ◽  
...  
Keyword(s):  
Risk Factors ◽  
Deep Vein Thrombosis ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Duplex Ultrasound ◽  
Iliac Vein ◽  
Vein Thrombosis ◽  
Below The Knee ◽  
Clinical Conditions ◽  
Deep Vein

BACKGROUND: Symptoms and clinical signs suggestive of deep vein thrombosis (DVT) are common but may have numerous possible causes. OBJECTIVES: 1) To identify the most frequent clinical symptoms and correlate them with duplex ultrasound scan (DS) findings; 2) to identify high-risk clinical conditions for DVT; and 3) to evaluate time since the onset of symptoms and DS examination. METHODS: A total of 528 patients with a clinical suspicion of DVT were evaluated by DS performed by experienced vascular ultrasonographists. RESULTS: DVT was present in 192 (36.4%) of the patients. The external iliac vein was involved in 53 patients (10.04%), the femoral veins in 110 (20.83%), the popliteal vein in 124 (23.48%), and veins below the knee were involved in 157 (29.73%) of the cases. Limb swelling was present in 359 cases (68%), and 303 (57.4%) complained of pain. Sixty nine patients received a DS due to suspected or proven pulmonary embolism (PE); 79 patients were in postoperative period. In the multivariate analysis, independent risk factors for DVT included age>65 years (OR=1.49; 95% confidence interval [95%CI] 1.01-2.18; p=0.042), edema (OR=2.83; 95%CI 1.72-4.65; p<0.001), pain (OR=1.99; 95%CI 1.3-3.05; p=0.002), cancer (OR=2.32; 95%CI 1.45-3.72; p<0.001), and PE (OR=2.62; 95%CI 1.29-5.32; p=0.008).Time since the onset of symptoms did not differ between the groups. CONCLUSIONS: In the present study, 36.4% of the patients referred to DS had DVT. Age > 65 years, presence of limb swelling, pain, cancer, and suspected or proven PE should be considered as major risk factors for DVT.

scholarly journals Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3911-3917 ◽  
Author(s):  
Grace H. Ku ◽  
Richard H. White ◽  
Helen K. Chew ◽  
Danielle J. Harvey ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Venous Catheter ◽  
Population Based ◽  
Older Age ◽  
Myelogenous Leukemia ◽  
Vein Thrombosis ◽  
Chronic Comorbidities

Abstract A population-based cohort was used to determine the incidence and risk factors associated with development of venous thromboembolism (VTE) among Californians diagnosed with acute leukemia between 1993 to 1999. Principal outcomes were deep vein thrombosis in both the lower and upper extremities, pulmonary embolism, and mortality. Among 5394 cases with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE was 281 (5.2%). Sixty-four percent of the VTE events occurred within 3 months of AML diagnosis. In AML patients, female sex, older age, number of chronic comorbidities, and presence of a catheter were significant predictors of development of VTE within 1 year. A diagnosis of VTE was not associated with reduced survival in AML patients. Among 2482 cases with acute lymphoblastic leukemia (ALL), the 2-year incidence of VTE in ALL was 4.5%. Risk factors for VTE were presence of a central venous catheter, older age, and number of chronic comorbidities. In the patients with ALL, development of VTE was associated with a 40% increase in the risk of dying within 1 year. The incidence of VTE in acute leukemia is appreciable, and is comparable with the incidence in many solid tumors.

scholarly journals Sonographic and Clinical Features of Upper Extremity Deep Venous Thrombosis in Critical Care Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Michael Blaivas ◽  
Konstantinos Stefanidis ◽  
Serafim Nanas ◽  
John Poularas ◽  
Mitchell Wachtel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critical Care ◽  
Upper Extremity ◽  
Strong Predictor ◽  
Venous Catheter ◽  
Acute Thrombosis ◽  
Vein Thrombosis ◽  
Therapeutic Anticoagulation ◽  
Deep Vein ◽  
Critical Care Patients

Background-Aim. Upper extremity deep vein thrombosis (UEDVT) is an increasingly recognized problem in the critically ill. We sought to identify the prevalence of and risk factors for UEDVT, and to characterize sonographically detected thrombi in the critical care setting.Patients and Methods. Three hundred and twenty patients receiving a subclavian or internal jugular central venous catheter (CVC) were included. When an UEDVT was detected, therapeutic anticoagulation was started. Additionally, a standardized ultrasound scan was performed to detect the extent of the thrombus. Images were interpreted offline by two independent readers.Results. Thirty-six (11.25%) patients had UEDVT and a complete scan was performed. One (2.7%) of these patients died, and 2 had pulmonary embolism (5.5%). Risk factors associated with UEDVT were presence of CVC [(odds ratio (OR) 2.716,P=0.007)], malignancy (OR 1.483,P=0.036), total parenteral nutrition (OR 1.399,P=0.035), hypercoagulable state (OR 1.284,P=0.045), and obesity (OR 1.191,P=0.049). Eight thrombi were chronic, and 28 were acute. We describe a new sonographic sign which characterized acute thrombosis: a double hyperechoic line at the interface between the thrombus and the venous wall; but its clinical significance remains to be defined.Conclusion. Presence of CVC was a strong predictor for the development of UEDVT in a cohort of critical care patients; however, the rate of subsequent PE and related mortality was low.

Risk Factors for Development of Symptoms Post Autologous Transplant for Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1771-1771
Author(s):  
Erica Campagnaro ◽  
Rima Saliba ◽  
Karen Anderson ◽  
Linda Roden ◽  
Floralyn Mendoza ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Symptom Burden ◽  
Disease Status ◽  
Female Gender ◽  
Patient Characteristics ◽  
The United States ◽  
Charlson Score ◽  
Female Ratio ◽  
Post Transplant

Abstract Background: Multiple myeloma (MM) is the most common indication for autografting in the United States. Although safe, autografting can be associated with substantial morbidity due to the toxic side effects of chemotherapy. Strategies aimed at minimizing symptoms post autografting may result in better tolerance. The risk factors for symptom development post autografting for MM have not been well characterized. Purpose: To define pretransplant conditions which may be predictive of post-transplant symptom burden. Methods: We performed prospective evaluation of symptom burden among 64 myeloma patients undergoing autograft at MDACC as well as retrospective review of pretransplant variables including patient demographics, performance status, albumin, disease status, and Charlson Comorbidity Index (CCI). Univariate analysis was performed to correlate pretransplant variables with posttransplant symptom burden as defined by M.D. Anderson Symptom Inventory (MDASI) scores at different timepoints post transplant. Results: 64 patients were studied from 6/2000 to 5/2003. Patient characteristics are summarized in Table 1. Symptom burden increased from baseline to day 0 to nadir, with most patients returning to their baseline by day 30 post transplant (Figure 1). Table 2 summarizes the potential impact of pre-transplant variables on median MDASI scores at nadir. Patients with the highest MDASI scores at baseline had the highest MDASI scores at nadir in quartile analysis(p=.001). Patients with Charlson score of ≥ 3, age &gt; 60, β 2M &gt; 3, albumin ≤ 4, and female gender had a trend towards higher nadir MDASI scores. Other pre-transplant variables, including Durie-Salmon stage, LDH, hemoglobin, disease status at time of autograft, and time from diagnosis to autograft had no apparent correllation with symptom burden throughout transplant (data not shown). Conclusions: Autografting for MM is associated with significant but reversible symptom burden during the first 30 days of the procedure. Baseline symptom burden is the most important predictor of post transplant symptom burden. Other potential predictors include Charlson score, age, β 2M, albumin, and female gender. The MDASI scoring system is a potentially useful means of following symptom burden post autografting that could be used to assess interventions aimed at reducing transplant related morbidity in MM patients. Patient Characteristics Median (range) Age at transplantation, years 55.2 (30–74) Time to SCT, months 7.5 (2.5–73.3) Albumin at transplantation 3.74 (2.9–4.5) β2M at transplantation 3.79 (1.4–19.3) Charlson score at transplantation 3.48 (2–6) Disease status at transplantation n (%) First remission 42 (65.6) Primary refractory 14 (21.9) Other 8 (13.6) Preparative regimen n (%) Melphalan 53 (82.8) Other 11 (17.2) Male to female ratio 1.5 : 1 Impact of Pre-transplant Variables on Nadir MDASI Scores n Median (range) Charlson score &lt; 3 50 22 (1–97) ≥ 3 14 41 (3–72) .09 Age ≤ 60 years 43 23 (1–97) &gt; 60 years 21 31 (3–72) .2 β 2M ≤3.0 34 20 (1–85) &gt; 3.0 27 28 (4–97) .2 Albumin ≤ 4.0 50 27 (1–97) &gt; 4.0 14 19 (1–16) .2 Gender Female 26 30 (5–85) Male 38 23 (1–97) .2 Figure Figure

Upper Extremity Deep Vein Thrombosis - Incidence, Risk Factors, and Management. The Worcester Venous Thromboembolism Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 584-584
Author(s):  
Frederick A. Spencer3 ◽  
Robert J. Goldberg ◽  
Darleen Lessard ◽  
Cathy Emery ◽  
Apar Bains ◽  
...  
Keyword(s):  
Risk Factors ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Central Venous Catheter ◽  
Lower Extremity ◽  
Upper Extremity ◽  
Venous Catheter ◽  
Central Venous ◽  
Vein Thrombosis ◽  
Deep Vein

Abstract Background: Recent observations suggest that upper extremity deep vein thrombosis (DVT) has become more common over the last few decades. However the prevalence of this disorder within the community has not been established. The purpose of this study was to compare the occurrence rate, risk factor profile, management strategies, and hospital outcomes in patients with upper versus lower extremity DVT in a cohort of all Worcester residents diagnosed with venous thromboembolism (VTE) in 1999. Methods: The medical records of all residents from the Worcester, MA statistical metropolitan area (2000 census=478,000) diagnosed with ICD-9 codes consistent with possible DVT and/or pulmonary embolism at all 11 Worcester hospitals during the years 1999, 2001, and 2003 are being reviewed by trained data abstractors. Validation of each case of VTE is performed using prespecified criteria. Results: A total of 483 cases have been validated as acute DVT events - this represents all cases of DVT occurring in residents of the Worcester SMSA in 1999. For purposes of this analysis we have excluded 4 patients with both upper and lower extremity DVT. Upper extremity DVT was diagnosed in 68 (14.2%) of patients versus 411 (85.8%) cases of lower extremity DVT. Patients with upper extremity DVT were younger, more likely to be Hispanic, more likely to have renal disease and more likely to have had a recent central venous catheter, infection, surgery, ICU stay, or chemotherapy than patients with lower extremity DVT. They were less likely to have had a prior DVT or to have developed their current DVT as an outpatient. Although less likely to be treated with heparin, LMWH, or warfarin they were more likely to suffer major bleeding complications. Recurrence rates of VTE during hospitalization were very low in both groups. Conclusions: Patients with upper extremity DVT comprise a small but clinically important proportion of all patients with DVT in the community setting. Their risk profiles differs from patients with lower extremity DVT suggesting strategies for DVT prophylaxis and treatment for this group may need to be tailored. Characteristics of Patients with Upper versus Lower Extremity DVT Upper extremity (n=68) Lower extremity (n=417) P value *Recent = < 3 months Demographics Mean Age, yrs 59.3 66.5 <0.001 Male (%) 51.5 45 NS Race (%) <0.05 White 86.6 91.6 Black 1.5 3.2 Hispanic 9.0 2.0 VTE Setting (%) <0.001 Community 53.8 76.2 Hospital Acquired 46.2 23.8 Risk Factors (%) Recent Central Venous Catheter 61.8 11.9 <0.001 Recent Infection 48.5 32.4 <0.01 Recent Surgery 47.8 28.1 <0.001 Cancer 44.1 32.6 0.06 Recent Immobility 38.2 47.0 NS Recent chemotherapy 25 9.5 <0.001 Renal disease 23.5 1.7 <0.0001 Recent ICU discharge 23.5 15.1 0.07 Recent CHF 19.1 16.6 NS Previous DVT 3.0 18.7 <0.01 Anticoagulant prophylaxis (%) During hospital admission (n=125) 76.7 71.6 NS During recent prior hospital admission (n=188) 73.7 54.7 <0.05 During recent surgery (n=146) 62.5 55.3 NS Hospital therapy - treatment doses (%) Any heparin/LMWH 66.2 82 <0.01 Warfarin at discharge 53.1 71.2 <0.01 Hospital Outcomes (%) Length of stay (mean, d) 11.2 6.8 <0.01 Major bleeding 11.8 4.9 <0.05 Recurrent DVT 1.5 1.0 NS Recurrent PE 0 0.2 NS Hospital Mortality 4.5 4.1 NS

Serum C-Terminal Telopeptide Maintains Its Correlation with Bone Disease in Myeloma Patients Even Under Treatment with Bisphosphonates

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4003-4003
Author(s):  
Lara Pochintesta ◽  
Silvia Mangiacavalli ◽  
Federica Cocito ◽  
Cristiana Pascutto ◽  
Alessandra Pompa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Type I Collagen ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Positive Association ◽  
Disease Status ◽  
Serum Levels ◽  
Patient Specific ◽  
Type I

Abstract Abstract 4003 Skeletal related events (SREs) are a significant cause of morbidity and mortality in multiple myeloma (MM). Markers of bone turn-over, in particular serum C-terminal telopeptide of type I collagen (CTX), can be used for monitoring early signs of bone damage either in osteoporosis or in neoplasm such as Multiple Myeloma. Since serum CTX levels are significantly decreased during bisphosphonate treatments (Dennis, N Engl J Med 2008), it is not clear whether serum CTX monitoring still retain a role in predicting SREs once bisphosphonate treatments was started. Aim of this study was to test whether serum CTX monitoring significantly correlates with active bone disease in a population of MM patients irrespective of concomitant bisphosphonate treatment. An unselected cohort of 87 patients with multiple myeloma diagnosed at our Hematology Division with the following characteristics entered this study: the availability of a baseline determination of serum CTX prior to start bisphosphonate therapy, multiple sequential serum CTX determinations (≥2 performed with an interval of at least 4 weeks), a radiologic evaluation available at the time of any SREs. The study was approved by our local ethical committee and conducted according to Helsinki Declaration guidelines. Patients baseline characteristics were the following: M/F 59%/41%, median age 60 (range 37–86), Durie and Salmon stage I/II/III (11%/14%/75%). During the study period (median follow-up 2.8 year, range 0.4–21 years), 73 patients (83%) experienced at least one SRE. Development of SRE was evaluated by standard skeletal x-ray, CT or MRI scan. Serum CTX was measured by an enzyme chemiluminescence method. A total of 260 serum CTX determinations were available for statistical analysis (median number of determinations for each patient 3, range 2–9). Univariate analysis found a statistically significant association between serum CTX and bone disease status with higher values in patients with active lytic lesions when compared to patients without radiological evidence of bone disease (median value 0.411 vs 0.356, p<0.001). By contrast, we observed significantly lower serum CTX values in patients under bisphosphonates treatment (median value 0.160 vs 0.355, p=<0.001). Association between serum CTX values, bone disease status and active bisphosphonates treatment was analyzed with a time-series linear model, accounting for measurement being repeated sequentially on each patient (random-effects GLS regression). Bone disease status and bisphosphonates treatment resulted significantly and independently associated to serum CTX (regression coefficient 0.222, 95%CI: 0.107–0.338, p<0.001 and 0.208 95%,CI: 0.320–0.096, p<0.001 respectively for bone disease status and bisphosphonates, cfr Tab 1). In addition, variations of CTX serum levels correlated significantly with the presence of active bone disease even under treatment with bisphosphonates (p<0.001). In conclusion, this study confirmed a positive association between serum CTX and presence of active bone disease. In addition serum CTX levels show a significant decrease under treatment with bisphosphonates. Taking into account these observations, patient-specific variations rather than the absolute serum CTX value should be used for detecting the onset of new SREs during a concomitant bysphosphonates treatment. Tab 1: Levels of serum CTX according to bone disease status and bisphosphonates treatment. Bisphosphonates treatment Progression in bone disease Active None Yes 0.219 (0.03–1.79) 0.533 (0.02–4.14) No 0.139 (0.03–0.69) 0.345 (0.071–1.57) Disclosures: No relevant conflicts of interest to declare.

Retrospective Study Of Incidence Of Thromboses In Chinese Versus African Americans With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1121-1121
Author(s):  
Radha Raghupathy ◽  
Sabarish Ayyappan ◽  
Dhivya Prabhakar ◽  
Frankie KF Mo ◽  
Erica L. Campagnaro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Retrospective Study ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Chinese Patients ◽  
Asian Patients ◽  
Venous Thromboembolic Events ◽  
The Difference

Abstract Background Risk of arterial (ATE) and venous thromboembolic events (VTE) is increased in multiple myeloma (MM). Immunomodulator therapy (Imid) concurrent with steroids further increases this risk. Retrospective single arm studies suggest that Asian patients with MM may have a lower risk of TE than in other ethnicities. We performed a retrospective study comparing Chinese (C) and African American (AA) patients in two centers, the Department of Clinical Oncology, Prince of Wales Hospital, the Chinese University of Hong Kong (PWH) and the University hospitals, Case Medical Center, Cleveland, Ohio (CMC), for ethnic differences in incidence of TE in MM. Methods 120 Chinese patients from PWH and 100 AA patients from CMC fulfilling IMWG consensus criteria for MM diagnosis between Jan 1st 2000 and Dec 31st 2011 were identified and selected for analysis. Data regarding demographics, comorbidities, myeloma characteristics, therapy and thrombotic complications were collected by electronic and paper chart review. Data collection was censored as of Dec 31st 2012. Results The Chinese cohort comprised more men, lower baseline incidence of diabetes (DM), hypertension (HTN) and non-myeloma related renal failure (CRF), advanced myeloma at diagnosis and more IgA subtype than AA. Over 90% of patients of both groups received chemotherapy. 72% of Chinese and 80% of AA received Imid based treatment. Lenalidomide with steroids was used more often in AA (36.8% AA vs 3.6%C, p<0.0001), Chinese received more thalidomide with steroids. (62.2% C vs 42.1%, p:0.004) Use of thromboprophylaxis (TP) is not routine in PWH, less Chinese were on TP during the disease course (11.7% vs 68%, p<0.0001) or during Imid based treatment. (16% vs 85%, p: 0.0001) Relative rates of aspirin, low molecular weight heparin and warfarin usage for TP were similar across both groups. Despite lower TP rates, a significantly lower rate of symptomatic VTE was observed in the Chinese. (3.3% vs 22%, p:0.001) The difference in VTE detection persisted on correction for number of imaging studies performed, 24 imaging tests in Chinese and 145 in AA. (16.7% vs 48.3%, p:0.004). Amongst the Chinese, all 4 events (100%) occurred on thalidomide dexamethasone (TD), 3 events (75%) in the absence of TP. In the AA, 21 of 26 events (81%) occurred on Imid based treatment. 12 events (46%) occurred in the absence of TP. On binary logistic regression using race, gender, prior venous thrombosis, any TP, TD and lenalidomide dexamethasone therapy as covariates, AA race (OR: 5.022, 95% CI:1.3- 19.4) and TD therapy (OR: 4.07, 1.26- 3.13) emerged as significant risk factors for VTE. Overall incidence of VTE on TD treatment was 4.5% in Chinese versus 22% in AA. (p:0.002) An increased number of arterial events were seen in the Chinese (9.2% vs 3% in AA) but the difference did not reach statistical significance. Of the 11 arterial events in Chinese, 5 (46%) occurred on Imid based therapy, 9 events (82%) were in the absence of TP. 7 were cardiac and 4 cerebrovascular. Of the 3 arterial events in AA, 1 (33.3%) occurred on Imids and all patients were receiving TP. 1 was cardiac, 1 abdominal and 1 upper limb. Conclusion Our study suggests that the Chinese have a lower risk of VTE than AA in the setting of MM. However , despite lower prevalence of most vascular risk factors in Chinese, ATE rates in Chinese were higher than AA, while not statistically significant. Larger studies are necessary to further elucidate these differences in thrombosis risk and to develop specific guidelines for TP in Asian patients with MM Disclosures: No relevant conflicts of interest to declare.

Polyclonal Gamma Globulin Suppression and Risk Of MGUS Progression Into Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1875-1875 ◽  
Author(s):  
Jawad Z. Sheqwara ◽  
Mohammad Alhyari ◽  
Shannon Keating ◽  
Philip Kuriakose
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Plasma Cell ◽  
Total Protein ◽  
Gamma Globulin ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
M Protein ◽  
Plasma Cell Dyscrasia ◽  
Female Ratio

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is the most common form of plasma cell dyscrasia, with a prevalence of 3% in the general population above age of fifty. MGUS has a malignant evolution rate of 1% per year. Large longitudinal studies have suggested that virtually all patients diagnosed with multiple myeloma (MM) had a preceding MGUS, with 75 % having detectible Monoclonal (M) protein ≥8 years prior to diagnosis. It is important to identify the features at diagnosis that can predict neoplastic transformation to MM. Purpose We identified 239 patients at our institute in whom MGUS was diagnosed between 2000 and 2010. The presenting clinico-hematologic features were correlated with the frequency of evolution into MM to identify early predictors of evolution. The primary end point was progression to MM. Results The patients' mean age was 70.7 years. The Male/Female ratio was 0.7. The mean concentration of the M component (MC) was 0.7 g/dL. IgG was the most frequent MC (77%), followed by IgA (13%). The median ratio of MC protein to total protein was 0.5. Single or multiple background polyclonal (PC) suppression was noted in 36% of patients. PC suppression of 50% or more was noted in 20.1% of patients, 49.8% had < 50% and 30.1% had no suppression. Mean bone marrow plasma cell percentage was 4.5 percent and mean hemoglobin was 12.4 g/dL. Eighteen of the 239 patients with MGUS progressed into MM over ten years of follow up. Univariate comparisons of all variables between those who progressed and those who did not, showed that the initial concentration of the serum M protein, ratio of M protein to the total protein, number of PC gamma globulins suppressed, degree of PC suppression and IgM gamma globulin suppression were statistically significant risk factors that correlated with progression into MM. Fourteen out of eighteen patients with progressive disease had either PC suppression or background IgM suppression. Conclusions Monoclonal protein concentration, ratio of M protein to the total protein and abnormal serum free light chain ratio are simple variables that have been shown in multiple previous studies to predict the progression of MGUS into MM. In our study, we additionally found that number of PC suppressed, degree of suppression and IgM suppression are also key risk factors that can predict progression. We believe that these variables can be potentially applied into an approach that uses a detailed risk stratification system to predict which cases of MGUS will progress into MM and to provide more intensive monitoring for patients more likely to progress. Disclosures: No relevant conflicts of interest to declare.

Exchange Transfusion and Leukapheresis in Pediatric AML Patients with High Risk of Early Death for Bleeding and Leukostasis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3741-3741
Author(s):  
Ursula Creutzig ◽  
Claudia Rossig ◽  
Michael Dworzak ◽  
Arendt von Stackelberg ◽  
Wilhelm Woessmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Exchange Transfusion ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Early Death ◽  
Myelogenous Leukemia ◽  
Acute Monocytic Leukemia ◽  
Metabolic Disturbances

Abstract Background. The risk of early death (ED) due to bleeding and/or leukostasis is high in AML patients with initial hyperleukocytosis (white blood cell count [WBC] > 100 000/µl) and highest in those with hyperleukocytosis and mono- or myelomonocytic leukemia (FAB M4/M5). (Creutzig, et al 1987) Within the AML-BFM studies, emergency strategies for children with AML and high risk for bleeding and leukostasis included exchange transfusion (ET) or leukapheresis (LPh). In order to determine whether these interventions reduced the rate of ED, 1251 AML-BFM patients from the trials AML-BFM 98 and 04 were analyzed. Risk factors for ED and interventions performed were verified focusing on patients with hyperleukocytosis. Patients . 238 of 1251 (19%) AML-patients <18 years of age (FAB M3 excluded) presented with hyperleukocytosis. Twenty-three out of 1251 (1.8%) patients died by bleeding and leukostasis within 15 days from diagnosis, 18 (78%) of these 23 ED patients had hyperleukocytosis. Seventy-two patients received ET and 17 LPh (including 14 patients with WBC counts < 100 000/µl). 149 patients with hyperleukocytosis did not receive ET/LPh. The median age of patients receiving ET was significantly lower compared to those with LPh (3.5 years vs 12.6 years, p = 0.015). WBC counts were similar in both treatment groups (ET median 224 000/µl vs LPh 218 000/µl, p = 0.20). Results. The percentage of ED by bleeding/leukostasis increased with higher WBC counts and was highest in 105 patients with WBC > 200 000/µl (14.3%). The ED rates were even higher in patients with FAB M4/M5 and hyperleukocytosis >200 000/µl compared to others with WBC >200 000/µl (M4/M5 13/65 [20%] vs. others 2/40 [5%], p=0.04). Patients with WBC counts >200 000/µl did slightly better with ET or LPh compared to those without ET/LPh (ED rate 7.5 % vs 21.2 %, p=0.055). Patients with WBC between 100 000/µl and 200 000/µl received ET/LPh less frequently compared to those with WBC >200 000/µl (22/133 [17%] vs. 53/105 [50%]). ET/LPh was mainly given in case of clinical symptoms of bleeding or leukostasis or coagulopathies or insufficient reduction (or increase) of WBC counts despite low dose chemotherapy. 15/80 (19%) patients with FAB M4/5 and WBC 100 000-200 000/µl received ET/LPh and none of these patients died early. ET/LPh was even given in 14 patients with WBC <100 000/µl because of clinical symptoms of bleeding or leukostasis or coagulopathies or rising WBC counts. In multivariate analysis WBC >200 000/µl was the strongest independent risk factor for ED (hazard ratio =15.0, 95% confidence interval 4.9-46.3, p(chi)<0.0001). FAB M4/M5 subtypes, general condition grade 4 and initial bleeding were also significant risk factors. Application of ET/LPh seems to have a non-significant benefit for a reduced ED rate by bleeding/leukostasis (p=0.13). The assessment of the general clinical condition of the patients plays a major role for the decision for ET/LPh. However, this possibly selective cofactor could not be included completely in our calculation because of lack of standardized assessments and documentation of clinical reasons for decision making in particular in patients without ET/LPh. There was no difference in ED rates between ET and LPh. (2/17 vs 5/72, p =0.61). Compared to LPh, ET can be given without time delay. ET is easier to perform especially in young children who need smaller exchange volumes, as well as in adolescents where it can be applied also as partial ET. ET also corrects metabolic disturbances and avoids deterioration of coagulation. Conclusion. Our data confirm the high risk of bleeding/leukostasis in patients with hyperleukocytosis. Although we could only disclose a trend for a clinical benefit of ET/LPh in this retrospective analysis - probably due to some negative selection bias in patients with the intervention - we strongly advocate ET/LPh in AML patients with WBC >200 000/µl, and in particular in those with FAB M4/M5 subtypes or with clinical symptoms of bleeding or leukostasis or coagulopathies even with lower WBC (100 000/µl - 200 000/µl). Creutzig, U. et al. (1987) Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia: Associations with hyperleukocytosis and acute monocytic leukemia. Cancer,60, 3071-3079. Disclosures No relevant conflicts of interest to declare.

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