The Risk Factors of the Venous Thromboembolism in Hospitalized Patients with Hematologic Malignancies in the United States: National Inpatient Sample Analysis, 2011-2015

Abstract Background. Hospital course of patients with hematologic malignancies associated with multiple complications, such as venous thromboembolism (VTE) which significantly affects morbidity and mortality. Compared to the general population patients with hematologic malignancies carry series of risk factors of VTE. Goals of this study were to describe demographic characteristics as well as define the risk factors of VTE in hospitalized patients with hematologic malignancies. Our study was focused on acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), Non-Hodgkin's lymphoma (NHL), Hodgkin's Disease (HD), multiple myeloma (MM). Methods. Cohort selection. The Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ) for the years 2011 to 2015 was queried for the analysis. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and corresponding ICD-10-CM codes (for the period of 0ctober 1 - December 31, 2015) in order to identify patients with hematologic malignancies as a primary diagnosis for the hospitalization, and VTE as secondary diagnosis of the hospitalization. In order to determine comorbidities in selected population we used Clinical Classifications Software (CCS) in conjunction with ICD-9-CM codes. Statistical Analysis. Complex weights were used throughout all calculations, enabling appropriate national projections. Percentages in all tables and figures reflect national estimates. Chi-squared and independent t-tests were used for univariate analysis where appropriate. We performed logistic regression analyses to examine the association between risk factor and VTE. In our study p-value <0.05 was considered statistically significant. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results. A total of 80,078 patients with hematologic malignancies were hospitalized from 2011 to 2015. Males represented 56.1% of the population, majority of the patients were white (69.5%), greater part of the patients were older than 35 years of age (35-65 42.6%, >65 48.8%) (Table 1). Main comorbidities during hospitalization were anemia (58.1%), followed by hypertension (49.1%), fluid disorders (40.1%) and coagulopathies (24.5%) (data not shown). Rate of VTE in all patients was 5.3% and was evenly distributed among genders and races. Rate of VTE was highest in patients with AML (6.6%) followed by ALL (6.1%), and NHL (6.0%), and lowest in patients with MM (3.49%) followed by CLL (3.31%), and CML (3.31%) (Table 2). The highest risk of VTE among patients with hematologic malignancies were in patients receiving chemotherapy (OR=1.684 95% CI=1.567-1.809) followed by infections such as pneumonia (OR 1.313 95% CI 1.201-1.436) and sepsis (OR=1.66 95% CI=1.524-1.621). Other comorbidities such as congestive heart failure, liver disease, coagulation disorders and acute renal failure were associated with significantly higher risk of VTE with OR varying from 1.1 to 1.2. (Table 3) Conclusions. In this retrospective large US inpatient database analysis, we found that average rates of VTE in patients with hematologic malignancies was 5.3% and was highest in patients with AML. Patients receiving chemotherapy had highest risk of developing VTE during hospitalization followed by patients with infections such as sepsis and pneumonia. Higher rates of VTE in patients receiving chemotherapy and patients with sepsis was previously described, however our findings indicate that rate of VTE remain high in these population. Findings of our study can be used for development of the appropriate antithrombotic prophylactic strategies in hospitalized patients with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.

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Incidence and Outcomes of Acute Transfusion Reactions in Hospitalized Patients in the United States

Blood ◽

10.1182/blood-2020-138982 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 30-31

Author(s):

Rohit Kumar ◽

Sindhu Malapati ◽

Sunny R K Singh ◽

Bokhodir Mamedov ◽

Myra R Shah ◽

...

Keyword(s):

Risk Factors ◽

Conflicts Of Interest ◽

Multivariate Logistic Regression Analysis ◽

The United States ◽

Hospitalized Patients ◽

P Value ◽

Continuous Variables ◽

Blood Products ◽

Increased Risk ◽

Transfusion Reactions

Introduction Acute transfusion reactions (ATRs) have a broad spectrum of presentations ranging from benign to life-threatening. Due to the rarity of these reactions, there is a paucity of data regarding their incidence and clinical outcomes. The objectives of this study were to determine the incidence of ATRs, its risk factors, and associated mortality. Methods: We reviewed the National Inpatient Sample (NIS) database 2014 for admissions where the patient (>=18 years old) was transfused blood products. The NIS is a large publicly available all-payer inpatient healthcare database designed to produce U.S. regional and national estimates of inpatient utilization, access, charges, quality, and outcomes. ATRs were identified using ICD-9 CM codes for transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), febrile non-hemolytic transfusion reactions (FNHTR), acute infections, anaphylaxis, and acute hemolytic reaction. Pearson's chi-square and student's t-test were used to compare categorical and continuous variables between hospitalizations with versus without ATRs, respectively. Multivariate logistic regression analysis was done to determine the risk factors for common ATRs (TACO, TRALI, and FNHTR). A multivariate cox proportional model was built to compare the mortality of two study groups. A 2-sided p-value ≤ 0.05 was considered significant. Results: A total of 2,134,691 hospitalizations were associated with the transfusion of blood products. ATRs were documented in 0.2% of the hospitalizations (TACO 0.08%, TRALI 0.06%, FNHTR 0.09%, others 0.003%). The group that had ATRs was slightly younger (median age 67 vs 68 years, p=0.002), had the same proportion of females (58.3% vs 55.3%, p=0.055), less comorbidity score (28.7% vs 31.7% had Charlson Comorbidity Index >3, p=0.042) and more critically ill (17.8% vs 10.5% on mechanical ventilation, p<0.001) compared to group without ATRs. Hospitalizations with ATRs had longer median length of stay (7 vs 6 days, p<0.001) and higher median hospital cost ($64,399 vs $53,912, p<0.001) compared to without ATRs. The risk factors for common ATRs (odds ratio, OR) are mentioned in the table. ATRs were not associated with increased risk of mortality (combined HR 0.89 95%CI 0.71-1.12, p=0.321). Conclusions: Nationally, the incidence of ATRs is low in hospitalized patients and it is not associated with increased mortality. This large database analysis gives insight into the risk factors associated with different ATRs. Disclosures No relevant conflicts of interest to declare.

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Increasing Genetic Complexity Predicts for Inferior Outcomes Following Reduced-Intensity Conditioning Allogeneic Transplant for Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v118.21.3090.3090 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3090-3090 ◽

Cited By ~ 1

Author(s):

Samantha M. Jaglowski ◽

Nyla A. Heerema ◽

Patrick Elder ◽

John C. Byrd ◽

Steven Devine ◽

...

Keyword(s):

Multivariate Analysis ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Prognostic Indicator ◽

Lymphocytic Leukemia ◽

P Value ◽

Allogeneic Transplant ◽

Reduced Intensity Conditioning ◽

Genetic Complexity ◽

Reduced Intensity

Abstract Abstract 3090 Several biologic markers have been identified which predict an unfavorable course in CLL. Reduced-intensity conditioning (RIC) allogeneic transplant may be able to overcome some of these. This retrospective analysis evaluates the effect of cytogenetics, including metaphase cytogenetics, on outcomes with RIC-allogeneic SCT. From 2005–2011, 51 RIC-allogeneic SCTs were performed at The Ohio State University for CLL. There were 38 males (74.5%) and 13 females (25.5%) with a median age of 58 (range 37–73). The median interval between diagnosis and SCT was 48 months (range 9–270). Before SCT, a median 4 lines of chemotherapy were given (range 1–11). One patient was in CR at the time of SCT, 39 were in PR, and 11 had stable or progressive disease; the median CMI was 3 (range 0–7). Fifty-nine percent of patients had del17; 53% had 3 or more abnormalities on metaphase cytogenetics, and 37% had 5 or more abnormalities. The source was PBSC in 48 (94%), BM in 1 (2%) and CB in 2 (4%). Of the PB or BM SCTs, 19 donors (39.6%) were related and 29 (60.4%) were volunteer; 45 (92%) were matched and 4 (8%) had a 1 allele mismatch. There were 21 (41%) pairs with an ABO mismatch and 16 (31.4%) pairs with a gender mismatch. Conditioning was Flu/Bu +/− ATG in 42 patients (82.2%), FluCamTBI in 6 (11.8%), FluCy in 1 (2%), and FluCyTBI-based in 2 receiving CB (4%). Following transplant, 34 (66.6%) developed AGVHD (gr 1–2: 28, gr 3–4: 6) and 27 of 48 evaluable patients (56.3%) developed CGVHD (limited: 7, extensive: 20). With a median follow-up of 17.3 months (range 1–60), the estimated 3-year OS and PFS following transplant were 56.5% and 42.9% respectively. Table 1 lists variables which had a p-value of ≤0.1 on univariate analysis. The presence of del13 and ≥5 karyotype abnormalities remained significant on multivariate analysis for OS while ≥5 karyotype abnormalities and conditioning with an alemtuzumab-containing regimen were significant for PFS (Table 2). The estimated 3 year OS for patients with del13 was 32.2% and 23% for patients with ≥5 karyotype abnormalities, compared with 72.7% and 73.5% for those without, respectively. The estimated 3-year PFS was 21.5% for patients with ≥5 karyotype abnormalities and 0% for patients with an alemtuzumab-containing regimen and 53.9% and 49.3% for those without, respectively.Table.Variables included in multivariate analysis model.Variablelogrank p-valuePFSOSAge ≥550.0072*…Del13 ≥4.7%0.0039*Del17p ≥5.7%0.0019*0.0878Karyotype abnormalities ≥50.0002*0.0138*Karyotype abnormalities ≥30.0186*0.0623Largest node ≥4 cm0.0277*…Marrow involvement ≥50%0.0752…Alemtuzumab conditioning…0.0001*GVHD prophylaxis0.0001*0.0374*HLA mismatch<0.0001*…*statistically significant at p<0.05Table 2.Multivariate analysis of OS, PFS.OSVariableHR95% CIp-valueDel13q<4.7%1≥4.7%3.581.36 to 9.420.01Karyotype<41≥55.161.97 to 13.560.001PFSVariableHR95% CIp-valueConditioningno alemtuzumab1alemtuzumab9.83.28 to 29.290Karyotype<41≥54.351.67 to 11.280.002 Due to small numbers, the alemtuzumab data should be interpreted with caution, but are consistent with previous reports. Increasing genomic complexity is known to predict for diminished chemosensitivity. Accordingly, the presence of 5 or more abnormalities on metaphase cytogenetics was demonstrated to be a poor prognostic indicator for both PFS and OS following SCT. There was substantial, but not universal, overlap among patients with del17, del13, and highly complex karyotype; this interplay merits further consideration. Better understanding of the evolution of genetic complexity will better define how to time transplant to allow for maximum benefit to those patients likely to evolve.Figure 1.OS and PFS by KaryotypeFigure 1. OS and PFS by Karyotype Disclosures: No relevant conflicts of interest to declare.

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Postoperative Venous Thromboembolism in Children Is Increased in Setting of Cancer or Infection

Blood ◽

10.1182/blood.v128.22.2391.2391 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2391-2391

Author(s):

Harold J. Leraas ◽

Jina Kim ◽

Zhifei Sun ◽

Uttara P. Nag ◽

Brian D. Ezekian ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Venous Thromboembolism ◽

Pediatric Patients ◽

Conflicts Of Interest ◽

Significant Risk ◽

The United States ◽

Improvement Program ◽

Thrombotic Risk ◽

Factors Associated

Abstract Background: Venous thromboembolism (VTE) is an uncommon but clinically significant postoperative complication in children. Incidence of VTE in pediatric patients ranges from 34-58 per 10,000 hospitalized children1. Due to rarity of these events, there is limited information about the factors predisposing children to VTE after surgery. We queried a national surgical database to identify risks and outcomes associated with VTE in pediatric surgical patients. Methods: The National Surgical Quality Improvement Program-Pediatric (NSQIP) is a prospectively collected database that records pediatric surgical information, surgical approaches, and 30 day patient outcomes. The database was queried for the years 2012-2013 to identify pediatric patients (age < 18) who had received surgical intervention and were diagnosed with postoperative VTE. Because of their separate coding in NSQIP, we defined VTE as including venous thromboembolism, or pulmonary embolism (PE) diagnosed radiographically within 30 days of operation. To reduce non-random differences between patients we used propensity scores based on age, sex, race, BMI, and ASA classification to match patients in a 1:2 ratio using the nearest neighbor method. Using univariate and multivariate analysis, we identified preoperative risk factors associated with VTE. Results: In total, 130 patients were identified who developed VTE postoperatively (VTE n=122, PE n=7, BOTH PE + VTE n= 1) from this database of 114,395 patients. There were 104 patients with VTE that also had complete entries and were subsequently analyzed in this study. Surgical specialties treating patients in this analysis included cardiothoracic surgery, general surgery, neurosurgery, orthopedic surgery, otolaryngology, plastic surgery, and urology. Eighty-one unique operative CPT codes were identified for patients with VTE. Patients who developed VTE had increased operative time, anesthesia time, and total length of stay (all p < 0.001). Multivariate analysis demonstrated that pneumonia (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.3 - 2.29), Central Line Associated Bloodstream Infection (CLABSI) (OR 1.69, 95% CI 1.18 - 2.42), sepsis (OR 1.47, 95% CI 1.18 - 1.82), septic shock (OR 1.36, 95% CI 1.06 - 1.75), and current solid or hematologic malignancy or active treatment of malignancy (OR 1.30, 95% CI 1.08 - 1.58) were all statistically significant risk factors associated with development of VTE (all p < 0.05). Conclusions: Postoperative VTE risk is significantly increased in children with malignancy or severe infections. Further research is needed to understand the mechanism between malignancy, systemic inflammation, and VTE risk in children. These findings may help to identify patients in need of prophylactic treatment in order to reduce postoperative thrombotic risk in pediatric patients. References: 1. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124(4):1001-1008. Disclosures No relevant conflicts of interest to declare.

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2259. Predictors of Empiric Carbapenem Therapy in Complicated Intra-Abdominal Infections in the United States, 2013–2017: A Retrospective Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1937 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S773-S773

Author(s):

Marya Zilberberg ◽

Brian Nathanson ◽

Kenneth Lawrence ◽

Colby Johnson ◽

Kristen Ditch ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

The United States ◽

Generation Cephalosporin ◽

Hospitalized Patients ◽

P Value ◽

Multivariable Logistic Regression Model ◽

Abdominal Infections

Abstract Background Complicated intra-abdominal infections (cIAI) remain an important cause for hospitalization. Evidence-based guidelines recommend reserving broad-spectrum antibiotic coverage for high-risk cases in order to reduce overuse of certain antibiotic classes, particularly in the face of emerging carbapanem resistance. We examined the factors associated with use of empiric carbapenem treatment (ECT) among hospitalized patients with cIAI. Methods We performed a multicenter retrospective cohort study in the Premier database of approximately 180 hospitals, 2013–2017. Using an ICD-9/10 based algorithm including a requirement for a laparotomy/laparoscopy, we identified all adult patients hospitalized with cIAI and included those with a positive blood or abdominal culture. We derived and tested a multivariable logistic regression model to examine predictors of ECT. Results Among 321,317 hospitalized patients with cIAI, 4,453 (1.4%) were culture-positive, 1,185 (26.6%) of whom received ECT. Among those given ECT, >50% (682) had no risk factors for resistance, and in only 120 (10.1%) was an organism resistant to a third-generation cephalosporin (C3R extended spectrum β-lactamase [ESBL] phenotype) isolated. The top 5 variables associated with ECT use were: pre-cIAI anti-fungal therapy (OR 2.57, 95% CI 1.91, 3.45) urgent (vs. emergent) admission (OR 1.56, 95% CI 1.21, 2.01), corticosteroids (OR 1.50, 95% CI 1.13, 1.99), ICU admission (OR 1.46, 95% CI 1.17, 1.82), and presence of sepsis/septic shock (OR 1.43, 95% CI 1.18, 1.74). The model had a moderately good fit (c-statistic = 0.683; 95% CI (0.665, 0.700), Hosmer-Lemeshow P value = 0.411). Conclusion Among patients hospitalized with a cIAI, 26.6% received ECT despite >50% lacking risk factors for resistance, and an only 10% prevalence of C3R in this cohort. This suggests that there remains an opportunity for carbapanem-sparing strategies. Further stratification of the risk for resistance is needed among patients with markers of high illness severity, such as those identified in our model. Disclosures All authors: No reported disclosures.

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Polymorphisms in the CYP450 Genes Influences Regimen Related Toxicity and Outcome in Patients with Beta Thalassaemia Major Undergoing HSCT.

Blood ◽

10.1182/blood.v114.22.869.869 ◽

2009 ◽

Vol 114 (22) ◽

pp. 869-869

Author(s):

Poonkuzhali Balasubramanian ◽

Salamun Desire ◽

Vikram Mathews ◽

Kavitha M Lakshmi ◽

Shaji R Velayudhan ◽

...

Keyword(s):

Risk Factors ◽

Annual Meeting ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

P Value ◽

Thalassaemia Major ◽

Hematopoietic Stem ◽

Beta Thalassaemia ◽

Variant Genotype ◽

The Impact

Abstract Abstract 869 Polymorphisms in drug metabolizing enzymes are known to contribute to inter-individual differences in the pharmacokinetics (PK) of the two most commonly used drugs for conditioning for hematopoietic stem cell transplantation (HSCT), busulfan (Bu) and cyclophosphamide (Cy) and their metabolites in plasma. We have previously reported the impact of CYP genes on the PK of Cy, [Blood (ASH Annual Meeting Abstracts), Nov 2004; 104: 99] and the influence of Cy PK on transplant outcome [Blood (ASH Annual Meeting Abstracts), Nov 2004; 104: 1820]. We have now extended this study to evaluate a total of 19 polymorphisms in 11 genes that are known to be involved in the metabolism of Bu and Cy. 180 of the 276 patients with thalassemia major who underwent HSCT between March 1991 and Dec 2008 and for who genomic DNA was available were included in the study. The following polymorphisms were screened using PCR followed by RFLP and/ or gel electrophoresis: GSTA1*B, GSTM1 and GSTT1 deletion, GSTP1*B, CYP2B6*2, *3, *4, *5 and *6, CYP2C9*2, *3 and *4, CYP2C19*2, *3, CYP3A4*1B, CYP3A5*3, *6 and ALDH1A1*2 and ALDH3A1*2. Polymorphism frequencies were associated with regimen related toxicities, other transplant related complications using Fischer's Exact test and Cox-proportional hazard's model.. Significant associations are shown in the Table. On univariate analysis, CYP2B6*4 variant genotype was associated with incidence of hemorrhagic cystitis (HC); CYP2C9*3 variant genotype was associated with the severity of HC; CYP2C19*3 and 2C9*2 genotypes were associated with overall and even-free survival (OS and EFS) and CYP2C9*2 and CYP2C9*3 genotype was associated with transplant related mortality (TRM). Multivariate analyses performed adjusting for known clinical risk factors still showed these genotypes to be significantly associated with outcome parameters. Variant genotypes of polymorphisms that result in decreased metabolism of Cy are protective against regimen related toxicities while these polymorphisms were risk factors for EFS and OS in the present study. This is the first report on the influence of common GST, CYP and ALDH polymorphisms on outcome of HSCT in patients with thalassaemia major. Screening for these polymorphisms in patients with beta thalassaemia undergoing HSCT can help identify patients at higher risk of complications.Table:EndpointGenotypeRelative risk (95% CI)P- value HCCYP2B6*4 variant0.3 (0.13-0.889)0.028 HC grade 1 vs. HC grade 2-4CYP2C9*3 variant0.2 (0.073-0.962)0.043 TRM2C9*2 variant2.7 (1.08-6.77)0.034 2C9*3 variant2.3 (1.0-5.7)0.049 OS and EFS2C19*3 variant3.3 (1.2-9.3)0.018 2C9*2 variant1.3 (0.93-2.03)0.070 Disclosures: No relevant conflicts of interest to declare.

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PS02.181: RISK FACTORS AND TREATMENT OF DIAPHRAGMATIC HERNIA FOLLOWING IVOR-LEWIS OESOPHAGECTOMY FOR CANCER

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.181 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 173-173

Author(s):

Francesco Puccetti ◽

Paolo Parise ◽

Uberto Fumagalli Romario ◽

Andrea Cossu ◽

Stefano De Pascale ◽

...

Keyword(s):

Risk Factors ◽

Oesophageal Cancer ◽

Diaphragmatic Hernia ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Neoadjuvant Chemoradiotherapy ◽

Occurrence Rate ◽

P Value ◽

Ivor Lewis

Abstract Background Oesophagectomy is the mainstay of curative treatment for oesophageal cancer and post-oesophagectomy diaphragmatic hernia (PODH) represents a potentially life-threatening surgical complication characterized by an underestimated occurrence rate and unknown related risk factors. This study analyses the experience of two tertiary designated centers in order to evaluate key elements concerning development and treatment of PODH. Methods A cohort of consecutive patients affected by a clinically resectable oesophageal cancer (any T, any N and M0) underwent Ivor-Lewis oesophagectomy between March 1997 and April 2017 according to three different approaches: totally open incision procedure (OILO), hybrid (HILO) and totally mininvasive to esophagectomy (MILO). All patients were retrospectively observed in the context of a postoperative calendarised follow-up in order to record the incidence and postrepair results of PODH. Results 414 patients underwent Ivor-Lewis oesophagectomy for cancer and 22 (5.3%) developed PODH within a median follow-up period of 16 months (6 - 177). Surgical repair was generally applied by the mean of laparoscopic cruroplasty (77%) with a conversion rate of 24%. Postoperative morbidity did not include early recurrences but exclusively cardio-pulmonary complications (5 patients) with one case of respiratory failure leading to death. The discharge was reached after a median hospital stay of 6 days (2 - 95) while 3 recurrences (14%) occurred over a median follow-up period of 10.1 months. A wide univariate analysis identified statistically significant associations between PODH occurrence and the administration of preoperative chemoradiotherapy, the complete pathological response (CPR) and a lymph node harvest (LNH) larger than 33 stations (p-value of 0.016, 0.001 and 0.024 respectively). The strong influence of an extended LNH was confirmed by the multivariable analyses (0.026) along with CPR which should however be considered as longer survival-related bias. Conclusion The minimally invasive surgery and the neoadjuvant chemoradiotherapy represent a considerable part of multimodal treatment for oesophageal cancer presenting a not statistically significant association with PODH development while a LNH including more than 33 nodes resulted to be an independent risk factor mirroring the extent of surgical demolition in oesophagectomy. Disclosure All authors have declared no conflicts of interest.

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Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma. Incidence, Risk Factors and Outcomes

Blood ◽

10.1182/blood.v126.23.3968.3968 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3968-3968

Author(s):

Sabarish Ayyappan ◽

Dhivya Prabhakar ◽

Vinita Gupta ◽

Brenda Cooper ◽

Hillard M. Lazarus ◽

...

Keyword(s):

Risk Factors ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Patient Characteristics ◽

Hematologic Malignancies ◽

P Value ◽

First Line ◽

Bulky Disease ◽

First Line Therapy ◽

Line Therapy

Abstract Venous thromboembolism (VTE) is a frequent complication of hematologic malignancies, including lymphoid malignancies. VTE results in significant morbidity and mortality in lymphoma patients. There is limited information regarding the factors affecting the risk of VTE in diffuse large B cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. We conducted a retrospective analysis to identify risk factors affecting the incidence of VTE and the effect of this complication on patient outcome. Methods: We searched the hematologic malignancies database of University Hospitals Seidman Cancer Center for patients newly diagnosed with DLBCL between 2004 and 2014. Records were reviewed for baseline demographics, evidence of known risk factors for VTE, disease characteristics, treatment history and baseline laboratory values. The univariate probability of overall survival (OS) and progression free survival (PFS) was estimated using the Kaplan-Meier method. The cumulative incidence procedure was used to estimate the incidence of VTE. To identify risk factors for VTE, univariate analysis was conducted on the potential risk factors for VTE and variables with P-value .25 were selected for analysis in the multivariate logistic regression model. Results: 204 patients diagnosed with DLBCL were included. Patient characteristics are presented in table 1. The median age at diagnosis was 66 years and 63% had advanced stage at diagnosis. After a median follow up was 27 months, 34 patients (16.6%) presented a VTE, with a 3-year cumulative incidence of 13.7% (95% CI 9.2-20.3%). The VTE was a pulmonary embolism in 12 subjects (35%) and deep venous thrombosis in 22 patients (65%). The diagnosis of VTE was done in the presence of active disease in 23 subjects (67%) and the first VTE occurred during the first line of chemotherapy in 16 patients (47% of VTE). Risk factors identified by univariate analysis (table 2) included previous history of VTE, coronary artery disease and congestive heart failure, bulky disease, and absence of a complete response. Treatment with an anthracycline - containing regimen resulted in decreased risk of VTE. In multivariate analysis, only the presence of bulky disease, progressive disease after first line therapy and treatment with anthracyclines retained statistical significance (p = 0.05, 0.05 and 0.006, respectively). After a median of 27 months of follow up 113 patients had presented progression after first line therapy and 72 had died. Overall, 3-year PFS was 58.6% (95% CI 51-66.2%), with lower PFS in patients experiencing VTE (3-year PFS: VTE 34.8%; no VTE 64.4%, p=0.002). 3-year OS for the whole cohort was 70.2% (95% CI 63.1-77.3%). Patients who presented VTE had a 3-year OS of 51.3% vs. 74.8% in patients without VTE (p=0.002). DLBCL patients present a high risk of VTE, with approximately half of all VTE events occurring early in the course of the disease. We were able to identify the presence of bulky disease at diagnosis and the absence of response to first line therapy as risk factors for developing VTE. The use of anthracycline-containing regimens was protective against VTE, likely because of the increased rates of disease response. Patients with VTE had worsened outcomes, likely a result of the presence of persistent disease, although a direct effect of VTE on long-term outcomes cannot be ruled out. Our results highlight the need for a heightened awareness of the increased risk of VTE in DLBCL patients and the need for prevention strategies. Table 1. Baseline patient characteristics Median age, years (range) 66 (20-92) Gender (%) Male Female 115 (56.3%) 89 (43.6%) Stage I II III IV 32 (15.9%) 43 (21.4%) 41 (20.4%) 85 (42.3%) R-IPI 0 1-2 3-5 18 (8.8%) 104 (51.0%) 80 (39.2%) Table 2. Risk Factors and results of univariate analysis Risk factor Odds Ratio p value Age > 65 1.179 0.661 Male gender 0.847 0.659 Prior congestive heart failure 5.69 0.009 Prior VTE 4.016 0.07 Increased creatinine 3.479 0.181 Morbid obesity 5.121 0.252 Prior malignancy 1.283 0.674 Bulky disease 2.425 0.035 Stage II vs. I III vs. I IV vs. I 3.742 1.343 1.906 0.058 0.703 0.338 Elevated LDH 1.329 0.450 Hemoglobin <10g/dl 0.902 0.236 Platelets < 150,000/mcl 1 0.108 Non - GCB molecular subtype 0.658 0.439 Positive FISH for t(8;14) 1.668 0.568 Anthracycline 0.383 0.050 Rituximab 5.454 0.265 Response PR vs. CR PD vs. CR SD vs. CR 0.843 0.986 0.850 0.863 1.013 1.550 Disclosures No relevant conflicts of interest to declare.

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Granulocyte Transfusions at Appropriate Doses Improve Survival in Hematological Patients with Febrile Neutropenia

Blood ◽

10.1182/blood.v126.23.3566.3566 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3566-3566

Author(s):

Luciana Teofili ◽

Caterina Giovanna Valentini ◽

Nicola Piccirillo ◽

Roberta De Blasi ◽

Patrizia Chiusolo ◽

...

Keyword(s):

Conflicts Of Interest ◽

Fungal Infections ◽

Univariate Analysis ◽

Disease Status ◽

Lymphocytic Leukemia ◽

Attributable Mortality ◽

P Value ◽

Klebsiella Pneumonia ◽

Hematological Patients ◽

Value Range

Abstract Introduction. The granulocyte transfusions (GTXs) are used to booster antimicrobial drugs in severely neutropenic hematological patients. However, the optimal GTX dose and the actual efficacy of this practice are debated. Methods. We retrospectively evaluated the infection-attributable mortality (IAM, i.e. the mortality at 30 days after the last GTX) in 84 consecutive patients with hematological malignancies receiving GTXs (January 2009- December 2014). The indications for GTXs were i) presence of absolute neutrophil count (ANC) <0.5 x 10^9/l ii) fever with evidence of bacterial or fungal infections or symptoms of infections and iii) unresponsiveness to appropriate antimicrobial therapies for at least 48 hours. Results. Among 84 patients, 101 infectious episodes requiring GTXs were recorded (422 transfusions in total). Patients characteristics are summarized in Table I. Bacterial infections were documented in 94 episodes (Klebsiella pneumonia in 35 cases, Escherichia coli in 16 and Pseudomonas aeruginosa in 13), invasive fungal infections (IFI) in 34 cases (including 18 pulmonary aspergillosis and 14 candidemia); 8 cases were considered as FUO. The infection was mono-microbial in 60 cases and poly-microbial in 33. Sepsis occurred in 67 cases. The overall IAM was 26.7 % (27 deaths among 101 infective episodes). At univariate analysis we failed to detect statistical association between IAM and several evaluated variables, either patient-related (age, sex, diagnosis, status of disease, allo-HSCT, aplasia duration) or infection-related (bacterial infection or IFI, sepsis, XDR, G-SCF concurrent administration) or GTX-related (number of GTXs received, PMN /Kg/course, PMN/Kg/day of neutropenia). However, when we grouped patients according to the value of the median dose of PMN per transfusion, we found that patients receiving 1.5 - 3 x 10^8/kg (GTXs A) had a lower IAM than patients receiving less than 1.5 (GTXs B) or more than 3 x 10^8 /kg (GTXs C) (15,7%, 35,3% and 44,4%, for GTXs A, B and C, respectively, p=0,014 at chi-square test). The dose's cut off were derived from the Guide to the preparation, Use and Quality assurance of Blood Components of the European Committee on Blood Transfusion (16th Edition). If the analysis was carried out by pooling together GTXs B and C, the association between PMN dose and IAM was even more pronounced (p value =0.006 at Fisher test for GTXs A versus GTXs B+C). At Kaplan-Meier analysis, the median survival was 59 days for GTXs A-patients and 30 days for GTXs B+C-patients (p =0,010). When patients with bacterial of fungal infections were separately evaluated, the effect of PMN dose on IAM was confirmed in bacterial (n=54, p=0,008) but not in fungal (n=23, p=0,588) infections. We then introduced the PMN dose (GTXs A or GTXs B+C) in a Cox proportional-hazards regression model together with variables with p<0.1 at univariate analysis (sepsis) or other clinically relevant factors (Allo-HSCT, age over 60 years, disease status categorized as onset/remission or relapse/resistance ). The PMN dose was the unique variable significantly associated with IAM (HR=3,0; 1,1-8,0 95% CI, p=0,020). Conclusions. These findings suggest that appropriate GTX doses can improve the post-infection survival of severely neutropenic hematological patients. Transfusion-related immunomodulation, leukostasis or transfusion-associated GVHD may underlie the detrimental effect of high PMN doses and deserve to be better explored. Table 1. Clinical characteristics of 84 patients treated with GTXs. A total of 101 courses were recorded. Characteristics Age (years, median value range) 46 (20-74) Male/Female 54/30 Underlying disease (n, %)Acute myeloid leukemiaLymphomaAcute lymphoblastic leukemiaMyelodysplastic syndromeMultiple myelomaChronic lymphocytic leukemia 63 (75%)12 (14%)5 (6%)2 (3%)1 (1%)1 (1%) Disease status at PMN transfusion (n, %)OnsetRelapse/resistanceComplete remission 49 (48,5%)41 (40.5%)11 (10.8%) Duration of neutropenia (days, median value, range) 18 (3-79) Site of infection (n, %)Sepsis LungBowelOthersMultiples (≥3 involved sites) 67 (66.3%)22 (21.9%)4 (3.9%)8 (7.9%)4 (4%) Allo-HSCTYes No 21(20.7)80(79.2) Transfusions per course (median value, range) 4 (1-14) PMN x 108/kg/course (median value, range) 8.78 (0.53-53.23) PMN x 108/kg/transfusion (median value, range) 2.11 (0.46-7.34) Disclosures No relevant conflicts of interest to declare.

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High Risk Factors of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for Leukemia.

Blood ◽

10.1182/blood.v114.22.4345.4345 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4345-4345

Author(s):

Jia Chen ◽

Feng Chen ◽

Wu Depei ◽

Aining Sun ◽

Huiying Qiu ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Risk Classification ◽

Lymphocytic Leukemia ◽

Disease Stage ◽

Great Promise ◽

Hematopoietic Stem ◽

High Risk Factors

Abstract Abstract 4345 Object To screen the high risk factors of relapse after allo-HSCT in acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) respectively, then to compare the contribution to relapse of each risk factor and explore the mechanisms which the factors take part in. Furthermore, to discuss the subsequent surveillance and treatment strategy after transplantation. Method This is a retrospective study of single center experience. We conduct 262 evaluable cases of leukemia which accepted allo-HSCT between the November, 2001 and the December, 2008, with 69 cases in ALL, 90 cases in AML and 103 cases in CML. Cox proportional hazard regression model is applied in single and multiple analysis to screen the high risk factors. Donor lymphocyte infusions(DLI) were administrated in 18 patients who relapsed after transplantation, and we describe the characteristics of this approach. Results The risk factors which affect relapse significantly are: ALL: Cytogenetic risk classification, the cycles of initial induction chemotherapy; AML: Cytogenetic risk classification, minimal residual disease (MRD) level before transplant, reconstitution of WBC, CD4+/CD8+ lymphocyte ratio in the graft; CML: disease stage before transplant. 9 of the 18 patients who had a lower tumor load benefited from the DLI. Conclusion Cytogenetic risk classification is the most relevant predictor of relapse after transplantation. DLI hold great promise to overcome the barrier of relapse, especially for patients with lower disease burden. Disclosures: No relevant conflicts of interest to declare.

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Investigation of CLL-Susceptibility Loci with Monoclonal B-Cell Lymphocytosis (MBL) Risk and Confirmation of Recently Reported CLL-Susceptibility Loci

Blood ◽

10.1182/blood.v116.21.2443.2443 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2443-2443

Author(s):

Susan Slager ◽

Kari Rabe ◽

Sara Achenbach ◽

Celine Vachon ◽

Lynn Goldin ◽

...

Keyword(s):

Mayo Clinic ◽

Conflicts Of Interest ◽

The United States ◽

European Population ◽

Lymphocytic Leukemia ◽

Control Measures ◽

Trend Test ◽

P Value ◽

Susceptibility Loci ◽

Single Nucleotide Variants

Abstract Abstract 2443 Background: There is strong and consistent evidence that a genetic component contributes to the etiology of chronic lymphocytic leukemia (CLL). A recent genome-wide association (GWA) study of CLL identified genetic variants located on chromosomes 2q13, 2q37.1, 6p25, 11q24, 15q23, and 19q13 that increased the risk of CLL within a European population. We replicated 5 of these 6 loci in an independent sample of CLL cases and controls from the United States. We now investigate whether these loci also influences MBL, a reported precursor condition of CLL. In addition, a follow-up analysis of the initial GWA study identified four more CLL-susceptibility loci on 2q37.3, 8q24.21, 15q21.3, and 16q24.1. Herein, we also evaluate the association of these four loci with risk of CLL. Methods: Peripheral blood samples were obtained from three ongoing studies: the Genetic Epidemiology CLL (GEC) Consortium, the Mayo Clinic non-Hodgkin lymphoma (NHL)/ CLL study, and the Mayo Clinic Biobank. We implemented rigorous genotyping quality-control measures, and successfully genotyped a total of 407 CLL patients, 965 controls, and 60 MBLs from these studies. Within each locus, the previously reported single nucleotide variants (SNPs) or variants in high linkage disequilibrium (LD) with the previously reported SNPs were evaluated with risk of MBL or CLL. Tests for association was done using the Cochran-Armitage trend test, and unconditional logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for CLL or MBL risk Results: In our evaluation of the six initially reported CLL-susceptibility loci (2q13, 2q37.1, 6p25, 11q24, 15q23, and 19q13) with MBL risk, we found three of the six had suggestive associations (p-value < 0.20) with ORs comparable to and in the same direction as those observed from CLL risk. Our strongest finding was with rs13397985 at locus 2q37.1 (OR= 1.56; 95% CI: 1.05, 2.31; p-trend = 0.041), followed by rs17483466 at locus 2q13 (OR= 1.49; 95% CI: 0.99, 2.24; p-trend = 0.074). As expected given our previously reported findings with CLL risk, the association between rs11083846 on chromosome 19q13 and MBL risk was not significant (p-trend = 0.70). Of the four recently reported CLL-susceptibility loci SNPs located on 2q37.3, 8q24.21, 15q21.3, and 16q24.1, we found all to be associated with CLL risk but one. Specifically, the strongest association was seen for locus 8q24.21 (best tagged SNP rs1021955; OR = 1.37; 95% CI: 1.10, 1.70; p-trend = 0.005), followed by locus 16q24.1 (best tagged SNP rs305065; OR= 0.77; 95% CI: 0.61, 0.97; p-trend = 0.024). However, we found no associations for locus 15q21.3 for the previously reported SNP nor for any SNPs in LD with the previously reported SNP. Conclusions: Our MBL results provide additional robust genetic evidence that MBL is a precursor to CLL and that it shares similar underlying genetic predisposition. Also our results confirm three of the four recently reported CLL-susceptibility loci and further support the role of a genetic basis in the etiology of CLL. More research is needed to elucidate the potential manner in which these genetic loci function in CLL or MBL. Disclosures: No relevant conflicts of interest to declare.

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