Clinical and Economic Outcomes Associated with Emergency Department Visits in Patients with Immune Thrombocytopenia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4209-4209
Author(s):  
Z John Lu ◽  
Mark D. Danese ◽  
Marc Halperin ◽  
Melissa Eisen ◽  
Robert Deuson

Abstract Abstract 4209 Introduction: Immune thrombocytopenia (ITP) is characterized by low platelet counts, spontaneous bruising, mucosal bleeding, and, more seriously, intracranial hemorrhage. The disease is associated with a high risk of complications, often requiring visits to emergency departments (ED), with possible subsequent hospitalization. To date, information about ED visits in ITP patients, including frequency, cost, hospitalization risk, and mortality risk, has not been well documented, although such data are critical to the understanding of the clinical and financial implications of poorly-controlled, chronic ITP. We used the 2007 Nationwide Emergency Department Sample (NEDS) to examine resource utilization, ED visits, and hospitalization charges in the US. Methods: The 2007 NEDS contains about 27 million ED records from over 970 hospitals in 27 Healthcare Cost and Utilization Project (HCUP) Partner States, representing a 20% stratified sample of US hospital-based ED visits. The database includes hospital and patient characteristics, diagnoses and procedures, disposition from ED including hospitalization and mortality, discharge diagnosis-related group (DRG) for subsequent hospitalizations, and total charges. Its large sample size enables analyses of relatively rare conditions such as ITP. All ED visits in the database were separated into two groups: visits with ITP as one of the diagnoses (ICD-9-CM diagnosis code of 287.31), and those without a diagnosis of ITP. Outcomes and resource use were separately evaluated in these two groups, as well as in several subgroups within the ITP group defined by age and whether the ITP diagnosis was the primary or a secondary diagnosis. Results: Approximately 8,348 (∼0.03%) of all ED visits in the 2007 NEDS database were in patients with ITP (28% as the primary diagnosis), of which nearly 60% were by female patients and 88% by adult patients (≥18 years old). Medicare or Medicaid was listed as the primary payer in 58% of the visits. Seventy-five percent of the ED visits in ITP patients led to hospitalizations, compared with less than 16% of ED visits in non-ITP patients (p < 0.0001). In ITP patients, 3% of the ED visits ended in death, compared with 0.6% in non-ITP patients (p < 0.0001). The mean total charges for ED visits in ITP patients were $1,650 compared with $1,495 for all others (p<0.0001). The average length of stay (LOS) during hospitalizations subsequent to ED visits was >1.5 days longer (6.5 vs. 5.0 days; p < 0.0001) for ITP patients. The mean total combined charges during the ED visit and resulting hospitalization were >60% higher ($47,000 vs. $29,000; p < 0.0001) for ITP patients. Subgroup analyses of ED visits in ITP patients by age showed that in the majority of visits by pediatric patients (<18 years old), ITP was identified as the primary diagnosis (61%) compared with only 24% among visits by adult patients. Furthermore, visits by adult ITP patients were less likely to result in routine discharge (18% vs. 50%), more likely to result in hospitalization (80% vs. 43%), and were associated with higher mortality compared with pediatric ITP patients (4% vs. 0.1%; p < 0.0001 for all comparisons). ED visits identified with ITP as the primary diagnosis were associated with a higher rate of subsequent hospitalizations (81% vs. 73%), but lower total charges and mortality ($1,490 vs. $1,710, and 2% vs. 4%) respectively, compared with those identified with ITP as a secondary diagnosis (p < 0.0001 for all comparisons). Conclusion: ED visits in ITP patients were associated with significantly worse outcomes, higher resource utilization, and greater total charges. For patients with ITP, younger age and a primary diagnosis of ITP were generally associated with better outcomes following ED visits. More robust and rigorous analyses controlling for patient and hospital heterogeneities will be conducted to confirm these findings. Disclosures: Lu: Amgen: Consultancy, Equity Ownership, Research Funding. Danese:Amgen: Consultancy, Research Funding. Halperin:Amgen: Consultancy, Research Funding. Eisen:Amgen: Employment, Equity Ownership. Deuson:Amgen: Employment, Equity Ownership.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 170-170
Author(s):  
Z John Lu ◽  
Mark D. Danese ◽  
Robert Herbert ◽  
Melissa Eisen ◽  
Robert Deuson

Abstract Abstract 170 Introduction: Immune thrombocytopenia (ITP) is a hemorrhagic disorder characterized by low platelet counts, spontaneous bruising, mucosal bleeding, and intracranial hemorrhage. In children ≤ 15 years old, the ITP incidence rate is approximately 2–5 cases per 100,000 person-years, with 30% of such cases considered as chronic ITP, which is characterized by persistently low platelet counts for at least 12 months after initial diagnosis. The disease burden of chronic ITP has not been well studied. Herein, we utilized an all-payer inpatient care database for pediatric discharges in the US to examine resource utilization, costs, and important clinical outcomes in hospitalized children with a diagnosis of ITP. Methods: The 2006 Kids' Inpatient Database (KID) was selected for this analysis. The KID is developed within the Healthcare Cost and Utilization Project (HCUP) sponsored by the federal Agency for Healthcare Research and Quality (AHRQ). Systematic random sampling is used to select 80% of all non-birth pediatric discharges, 10% of all non-complicated births, and 80% of all complicated births from all participating community and non-rehabilitation hospitals for inclusion. The 2006 KID database contains data on over 3 million unweighted discharges collected from over 3,700 hospitals in 38 states. This large sample size enables analyses of relatively rare conditions, such as pediatric ITP. ITP-related discharges were identified with the ICD-9-CM diagnosis code of 287.31, regardless of whether it was the principal diagnosis. We developed national estimates of the following: average total inpatient cost; average length of stay (LOS); incidence rates of costly procedures such as total splenectomy and blood transfusions (through ICD-9 procedure codes); incidence rates of serious complications such as septicemia, bacteremia, intracranial hemorrhage (through hospital DRG codes), and in-hospital death. Hospital charges were converted to costs using hospital-specific cost-to-charge ratios available in the database. In addition, subgroup analyses by the following age groups were conducted: 1 to 5, 6 to 9, 10 to 13, and 14 to 17, as well as by whether the ICD-9 code for ITP was the primary diagnosis or a secondary diagnosis on the discharge summary. Results: Approximately 4,274 (0.26%) of all non-birth-related discharges among patients aged 1–17 were in patients with ITP, including 3,633 identified with ITP as the principal diagnosis and 641 as a secondary diagnosis. The majority of hospitalizations in ITP patients occurred in large, teaching hospitals, and slightly over half were for girls. Close to 50% of the ITP hospitalizations occurred through emergency room admissions or transfers from other hospitals or healthcare facilities. The overall incidence of intracranial hemorrhage among ITP hospitalizations was 0.43%, confirming earlier studies. Total splenectomy occurred in approximately 1 in 25 (4.3%) such hospitalizations. The mortality rate during ITP hospitalizations was 0.38%, compared to 0.23% for all other hospitalizations; the difference was not statistically significant. The average LOS for ITP hospitalizations was shorter than for all other hospitalizations in the KID (2.4 vs. 3.6 days, p < 0.0001), but no significant difference in mean total inpatient costs was noted ($6,869 for ITP vs. $6,515 for all others), indicating that the complexity of hospitalization, and correspondingly the intensity of treatment, might have been greater in patients with ITP. A higher complication rate, greater resource utilization, and total costs were all associated with increasing age, with the oldest pediatric age group (14–17 years) experiencing the highest rate of blood transfusions and total splenectomy, the longest LOS, and the greatest total costs (p < 0.0001 for all). Hospitalizations in which ITP was listed as a secondary diagnosis were associated with significantly greater resource use and total costs compared with those where ITP was the primary diagnosis (p < 0.0001). Conclusion: Although hospitalizations in pediatric patients with ITP were not associated with greater LOS or mortality, they appeared to be associated with a greater intensity of resource use and per-day cost. Older age and ITP as a secondary diagnosis contributed to longer stay, more resource use, and higher total cost during hospitalization. Disclosures: Lu: Amgen: Consultancy, Equity Ownership, Research Funding. Danese:Amgen: Consultancy, Research Funding. Herbert:Amgen: Consultancy, Research Funding. Eisen:Amgen: Employment, Equity Ownership. Deuson:Amgen: Employment, Equity Ownership.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4544-4544
Author(s):  
Ronan T. Swords ◽  
Kevin R. Kelly ◽  
Devalingam Mahalingam ◽  
Stephen C. Cohen ◽  
Larry J. Miller ◽  
...  

Abstract Abstract 4544 Background The importance of bone marrow aspiration and biopsy in the evaluation of hematopoietic and non-hematopoietic disorders is well established. Recently, a new FDA-cleared battery powered bone marrow biopsy system was developed to allow operators access to the bone marrow space quickly and efficiently. Aims The first aim of this study was to evaluate the quality of core specimens using the new powered device compared to specimens obtained using the traditional manual technique in a swine model. The second aim was to evaluate the safety and efficacy of the device in patients presenting for outpatient hematology clinic visits. Materials and Methods For the pre-clinical evaluation of the device, three anesthetized pigs were used for the study. The powered device (OnControl, Vidacare Corporation, San Antonio, TX, USA) was comprised of a battery powered driver and needle set. The manual device used was a T-Handle Jamshidi bone marrow biopsy needle (Cardinal Health, Dublin, OH, USA). Core biopsy samples obtained were assessed for length and sample quality and then submitted for analysis to a pathologist blinded to the device used. The clinical evaluation of the device was conducted in accordance with practice guidelines and directions for use. Data collection included insertion success, time from insertion to removal, specimen quality, operator satisfaction with control/function of the device and overall operator satisfaction based on a scoring system (0-5; 0=totally unacceptable, 5=outstanding). Results Twenty six samples were collected from the swine model (19 samples using the powered device and 9 using the manual technique). No cellular artifact or thermal damage was reported in any of the samples obtained. The mean lengths for samples obtained using the powered and manual techniques were respectively 19.4mm±1.6mm and 18.6mm±5.3mm. For the clinical evaluation of the device, 16 patients were recruited from 2 centers. Mean insertion time was 11.25±3.39 seconds and mean time from needle contact with skin to needle removal was 38.5±13.94 seconds. No complications were reported. Five operators rated the overall use of the device as outstanding in 75% of cases. Conclusions In this study, the manual and powered samples were equivalent in specimen quality. The powered device however, captured longer biopsies when compared to the manual technique. In the patients evaluated, the device was easy to use as well as being safe and effective. The mean procedural time was significantly faster than previously reported with a manual technique. A randomized study of the powered device compared to the manual technique is underway. Disclosures: Swords: Vidacare Corporation: Research Funding. Kelly:Vidacare Corporation: Research Funding. Mahalingam:Vidacare Corporation: Research Funding. Cohen:Vidacare Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Miller:Vidacare Corporation: Employment, Equity Ownership. Philbeck:Vidacare Corporation: Employment, Equity Ownership. Brenner:Vidacare Corporation: Consultancy, Research Funding. Giles:Vidacare Corporation: Research Funding.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3983-3983
Author(s):  
Andrzej Hellmann ◽  
Simon A. Rule ◽  
Jan Walewski ◽  
Ofer Shpilberg ◽  
Huaibao Feng ◽  
...  

Abstract Abstract 3983 Background: Bortezomib is primarily metabolized by cytochrome P450 (CYP) 3A4 and 2C19 enzymes. Effects of co-administration of rifampicin (a potent CYP3A4 inducer) and dexamethasone (weak CYP3A4 inducer) on the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles of bortezomib were evaluated. Methods: Patients with relapsed or refractory multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) were enrolled in this open-label, 2-stage, parallel-group study. In stage 1, patients were randomized (1:1) to receive 3 cycles of bortezomib (1.3 mg/m2) on d 1, 4, 8, and 11 q3wk either alone or in combination with rifampicin 600 mg once-daily on d 4 to 10 of cycle 3 only. Stage 2 patients received bortezomib at same dose and schedule in combination with dexamethasone 40 mg once-daily on d 1 to 4 and d 9 to 12 of cycle 3 only. Patients could continue with bortezomib monotherapy for up to 10 cycles in case of clinical benefit. For PK/PD, blood samples were collected before and through 72 hours following bortezomib administration on d 11 of cycles 2 and 3. PK was the primary endpoint, secondary endpoints included PD (proteasome inhibition) and safety. Results: 61 patients were enrolled (39 MM, 22 NHL) in the study. 13 were treated with bortezomib + rifampicin, 18 with bortezomib + dexamethasone, and 30 with bortezomib only. Co-administration of rifampicin reduced the mean bortezomib maximum plasma concentration (Cmax) by approximately 23% (118 vs 93 ng/mL) and the mean area under plasma concentration-time curve from 0 to 72 hours (AUC72) by approximately 45% (223 vs 123 ng.h/mL). Co-administration of dexamethasone had no effect on mean AUC72 (179 vs 170 ng.h/mL). The mean bortezomib Cmax was 20% lower after co-administration of dexamethasone (140 vs 119 ng/mL); however this difference in Cmax was within the observed variability in Cmax during cycle 2 (CV=38%) and cycle 3 (CV=45%). Mean (SD) maximum percent proteasome inhibition (Emax) and area under percent proteasome inhibition-time curve from 0 to 72 hours (AUE72h) were comparable for bortezomib alone and in combination with rifampicin (Emax: 61.9 [4.56] vs. 62.3 [3.81] and AUE72h: 836 [323] vs. 777 [358]). Co-administration of dexamethasone did not affect the Emax (66.7 [4.27] vs. 61.8 [6.69]) or AUE72h (1329 [638] vs. 1157 [381]). Safety profiles were consistent with prior bortezomib experience in this population. Drug-related serious adverse events and treatment discontinuations were reported in 7/30 (23%) and 8/30 (27%) in bortezomib-only, in 3/13 (23%) and 3/13 (23%) in bortezomib + rifampicin, and 3/18 (17%) and 5/18 (28%) in bortezomib + dexamethasone subgroups. Investigator-assessed responses (CR+PR) were observed in 13/17 MM and 6/13 NHL patients in bortezomib-only, in 6/9 MM and 3/4 NHL patients in bortezomib + rifampicin, and in 10/13 MM and 2/5 NHL patients in bortezomib + dexamethasone subgroups. Conclusions: Co-administration of dexamethasone did not affect the PK or PD profiles of bortezomib. Co-administration of rifampicin reduced bortezomib exposure (AUC) by approximately 45%. Patients receiving bortezomib concomitantly with strong CYP3A4 inducers, such as rifampicin, should be monitored for reduction in clinical effect, while concomitant administration of weak CYP3A4 inducers, such as dexamethasone, is not expected to affect the bortezomib pharmacologic profile. Disclosures: Off Label Use: Discussion of Velcade in NHL subtypes other than mantle cell lymphoma is included. Rule:Johnson & Johson: Consultancy, Speakers Bureau; Roche: Consultancy. Walewski:Johnson & Johnson: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Investigators fee. Shpilberg:Johnson & Johnson: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Feng:Johnson & Johnson: Employment. van de Velde:Johnson & Johnson: Employment, Equity Ownership. Patel:Johnson & Johnson: Employment, Equity Ownership. Skee:Johnson & Johnson: Employment. Girgis:Johnson & Johnson: Employment. Louw:Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Key Oncologics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2195-2195 ◽  
Author(s):  
Russell K. Brynes ◽  
Attilio Orazi ◽  
Raymond S.M. Wong ◽  
Kalpana Bakshi ◽  
Christine K Bailey ◽  
...  

Abstract Abstract 2195 Introduction: Eltrombopag (epag), a thrombopoietin receptor agonist (TPO-RA), increases platelet counts in patients with chronic immune thrombocytopenia (cITP). TPO-RAs have been associated with varying degrees of increases in bone marrow reticulin (Brynes 2011; Ghanima 2011). Due to lack of pretreatment evaluations, the incidence and clinical significance of these findings have not been established. Inconsistencies in specimen preparation, staining, and analysis across institutions further confound conclusions. The purpose of this 2-year (y) study (NCT01098487) is to assess for bone marrow fibrosis (reticulin and/or collagen) in patients treated with epag for cITP. Baseline and 1y findings are presented. Methods: Bone marrow biopsies are being collected at baseline (before treatment with epag) and at 1 and 2y of treatment. Specimens are centrally processed and stained for reticulin (silver) and collagen (trichrome) and undergo central independent pathology review of cellularity; megakaryocyte, erythroid, and myeloid quantity and appearance; trabecular bone quality; reticulin grade; and presence of collagen (European Consensus scale-MF; Thiele 2005). Results: Baseline and 1y (10–14 months) data are available for 101 patients. Median age is 42y (18–78); 70 patients are female; 50% are Caucasian/European, 22% are East Asian, and 29% are Central South Asian. Median time since ITP diagnosis is 4.2y (0.2–45.7). All patients had received prior ITP therapy, and 8 patients had received prior TPO-RA treatment (epag [7], romiplostim [1]), the last dose ≥6 months before enrollment. At baseline, 91 patients had reticulin grade 0 (MF-0), 10 MF-1, and 0 MF≥2. At 1y, 59 patients had MF-0, 38 MF-1, 3 MF-2, and 1 MF-3 (Figure). Compared with baseline, there was no change at 1y in MF grade in 61 patients, a decrease by 1 grade in 3, an increase by 1 grade in 35, and an increase in 2 or 3 grades in 1 patient each (Table). Three patients had collagen at 1y (1 patient each with MF-1, MF-2, and MF-3). None of the 4 patients with MF≥2 had adverse events or hematologic abnormalities considered related to impaired bone marrow function, and none withdrew due to bone marrow findings. Among the 8 patients with prior TPO-RA treatment, all had baseline reticulin of MF-0 and none had collagen; at 1y, 6 remained MF-0, 1 was MF-1, and 1 MF-3 (collagen demonstrated). Cellularity was normal in 83% and 80% of patients at baseline and 1y, respectively. Other than normalization of erythroid lineage numbers, no changes occurred in marrow cellular composition. In 3 of 4 patients with MF≥2, cellularity was increased at 1y. Trabecular bone thinning was found at baseline in 28 patients (the majority with prior steroid use) and 51 patients at 1y. Discussion: 10% of patients had MF-1 at baseline. After 1y of treatment, no increase or a mild increase in reticulin was observed in 63% and 35% of patients. No patient with MF≥2 (n=4) had clinical signs or symptoms indicative of bone marrow dysfunction and none withdrew from the study. Results were similar to those reported for EXTEND, an eltrombopag extension study (median treatment duration >2 years; Brynes 2011). Conclusion: These data suggest that treatment with epag is generally not associated with clinically relevant increases in bone marrow reticulin or collagen. The potential association of TPO-RAs and increased bone marrow reticulin needs further study. Disclosures: Brynes: GlaxoSmithKline: Research Funding. Orazi:GlaxoSmithKline: Research Funding. Wong:Roche: Research Funding; MSD: Research Funding; Johnson & Johnson: Research Funding; Bayer: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biogen-Idec: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; GlaxoSmithKline: Research Funding; Bristol-Myers Squibb: Research Funding. Bakshi:GlaxoSmithKline: Employment, Equity Ownership. Bailey:GlaxoSmithKline: Employment, Equity Ownership. Brainsky:GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5561-5561 ◽  
Author(s):  
Shreekant V. Parasuraman ◽  
Ahmad B. Naim ◽  
Dilan C. Paranagama ◽  
Maureen Thyne ◽  
Sara Goldberger ◽  
...  

Abstract Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms (MPNs). Patients across all 3 MPNs experience marked disease burden in terms of symptoms and negative effects on quality of life (QoL), productivity, and activities of daily living (ADL). To improve the lives and health of patients with MPNs, it is also important to have a current understanding of these burdens from a financial standpoint. This analysis of MPN Landmark survey data examined the financial burden of patients who reported that their MPN affected their employment (ie, reduced work hours, discontinued employment, or went on medical disability) or experienced no such effects on their employment. Methods: Patients diagnosed with MF, PV, or ET were recruited to participate in a real-world retrospective study (MPN Landmark survey) in the US (fielded May - July 2014). Only respondents who were diagnosed before 2013 and were 16 to 65 years of age at the time of diagnosis were eligible for this analysis. Participants were asked if their MPN had an impact in terms of reduced work hours, discontinued employment, medical disability, or no impact; the first 3 categories were not mutually exclusive. Participants provided information on their annual household income in 2013 before taxes by selecting from the following categories: ≤$15,000, $15,001-$25,000, $25,001-$35,000, $35,001-$50,000, $50,001-$75,000, $75,001-$100,000, and >$100,000. The mid value of each range was used to calculate mean income levels within each subgroup evaluated. Results: A total of 813 patients completed the web-based Landmark survey and 369 eligible patients were included in this analysis (MF, 85; PV, 172; ET, 112). Median age among patients with ET was slightly lower than among patients with MF and PV at time of MPN diagnosis (ET, 48 years; MF, 56 years; PV, 53 years). The majority of respondents were women (MF, 62%; PV, 52%; ET, 75%). Almost all patients (99%) had health insurance, primarily group commercial insurance through an employer (MF, 46%; PV, 53%; ET, 57%) and Medicare (MF, 40%; PV, 34%; ET, 24%). Most patients had at least some college education (ie, some college, 4-year degree, or postgraduate degree): MF, 86%; PV, 90%; ET, 88%. The mean 2013 household income of patients with MF, PV, and ET were similar to each other ($79,800, $80,200, and $80,400, respectively) and slightly higher than the total 2013 US mean household income of $75,839. A notable proportion of patients in each MPN group reported that their disease led to reduced work hours, discontinued employment, and medical disability: MF, 38%, 35%, and 33%, respectively; PV, 33%, 28%, and 15%; ET, 28%, 21%, and 4%. Patient demographics, such as age and health insurance status, were similar among patients who reported MPN-associated effects on employment and patients who did not within each MPN. In each MPN group, the mean percentage household income loss in patients with reduced work hours, discontinued employment, and medical disability were: MF, 16%, 18%, and 28%, respectively; PV, 15%, 24%, and 17%; and ET, 0%, 24%, and 37%, compared with patients who did not experience any effects of their MPN on employment (Figure 1). Discontinued employment and medical disability tended to have a greater impact compared with reduced work hours across MPNs. Conclusion: Patients withMPNs may experience a considerable negative impact on their employment status, which in turn may be associated with reduced annual household income. Therefore, across all MPNs, forestalling or reversing discrete aspects of the diseases that negatively impact individual productivity is an important factor in the management of these chronic neoplasms. Disclosures Parasuraman: Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte Corporation: Employment, Equity Ownership. Thyne:Incyte Corporation: Speakers Bureau. Mascarenhas:Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Kalobios: Research Funding. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Miller:Incyte Corporation: Honoraria, Research Funding. Mesa:Promedior: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Pfizer: Research Funding.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 316-316
Author(s):  
Susan Paulukonis ◽  
Lisa Feuchtbaum ◽  
Elliott Vichinsky ◽  
Mary Hulihan

Abstract Background: High utilization of emergency department (ED) services among those with sickle cell disease (SCD) compared to the general population and compared to those with other chronic diseases is well documented in the literature. Some reports note that high utilization is episodic. Most analyses address the problem as a consistent one within patients, rather than consistent over time across the patient population but sporadic for patients. Reducing the high rate of ED utilization among patients with SCD requires an understanding of temporal patterns of ED utilization, the consistency of ED utilization over time by patients and the proportion of the population affected at any given time. Methods: CDC has developed the Sickle Cell Data Collection program (SCDC) to conduct state level surveillance in this disease, and to continue and improve upon work begun through the Registry and Surveillance System in Hemoglobinopathies (RuSH). Through SCDC, California has collected ED and hospitalization data for years 2005-2014 on 4,325 people with SCD. A period of high ED utilization among this cohort was defined as three or more ED encounters (either treat and release or admission to the hospital from the ED) for any diagnosis (not only SCD diagnoses) each fewer than 30 days from the prior visit. The start of an episode of high utilization is the date of the first ED encounter; the end is the date of the last eligible ED encounter. All cohort members were divided into categories of utilization using the proportion of time spent in periods of high utilization divided by the total time in cohort. Total time is cohort is defined as the length of time from the earliest appearance in the ED or hospital data 2005-2014 to the latest appearance. The five categories were defined as no episodes of high ED utilization, and approximate quartile groups for those with high ED utilization: 1.1 to 3.0%, 3.1-10.0%, 10.1% or greater. Age categories (pediatric is < 21 years, and adult is 21 years or older) are defined as patient age at close of study (end of 2014) or at death if prior. Patient ID beginning with P is a pediatric, A is adult in the figures. Results: There were 4,325 individuals with 27,694 person years in the cohort (mean 6.4 person years, median 7.6 person years). Sixty-three percent (n=2,715) of the cohort were aged 21 years and older. Forty-five percent, (n=1,955, 513 pediatric and 1,442 adults) had at least one episode of high utilization during the 10 year study for a total of 7,866 episodes of high utilization. Forty-three percent of patients with one or more high utilization episodes were male, and 63% were between the ages of 20 and 50. Nine percent of these high utilizing patients' total time in the cohort was made up of episodes of high utilization. The mean time span from start of episodes of high utilization to end of the episodes was 63.3 days, median 35 days; mean number of ED visits per episode was 9.0, median 4.0. Most episodes of high utilization were brief: 42.2% included just three visits, and 70.7% included five or fewer ED visits. Among these individuals with episodes of high utilization, the mean number of such episodes was 4.0 over the 10 years study period, and the median was 2.0. Most (76.4%) had five or fewer high utilization episodes, and 35.5% had just one (n = 693). Sample utilization patterns, including hospital admissions, are shown in Figure 1. Conclusions: We demonstrate that among individuals with SCD seen in a population-based, statewide surveillance system, periods of high ED utilization are common, but most SCD patients have only a limited number of short episodes of such utilization. We found that high ED utilization is episodic rather than consistent within individuals, and that while the range of time spent in episodes of high utilization varies, few patients are high utilizers of ED services over a long period of time. Statewide surveillance that follows individual patients over time and in different hospital settings and includes ED utilization (including visits not coded as being related to SCD), provides high quality public health information to inform clinicians and healthcare systems in their development of efforts to reduce ED utilization among those living with SCD. Figure 1 Figure 1. Disclosures Paulukonis: Pfizer: Research Funding; Biogen: Research Funding.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 65-65
Author(s):  
Heiner Zimmermann ◽  
Hairong Xu ◽  
Arie Barlev ◽  
Yang Zhang ◽  
Dhanalakshmi Thirumalai ◽  
...  

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and often aggressive disease in the setting of immunosuppression following solid organ transplant (post-SOT). About 50% of cases are associated with Epstein-Barr virus (EBV) infection of B cells, either due to reactivation of the virus after transplantation, or from primary EBV infection. Data remain very limited with respect to overall clinical and economic burden among EBV+PTLD patients (pts), particularly in the setting of pts who fail first line therapy. This retrospective chart review aimed to quantify the burden of hospitalization due to EBV+PTLD in post-SOT pts who failed first-line therapy in the real-world setting in Germany. Study Design and Methods: The German PTLD registry database was screened for pts with EBV+PTLD post-SOT who were refractory (failed to achieve complete [CR] or partial remission [PR]) to rituximab or rituximab plus chemotherapy (CT) or relapsed at any point after such therapy between 2000 to 2015. Pts with primary CNS PTLD were excluded. Pts without any outpatient visit or hospitalization record were excluded from the analysis (n of pts=1). Hospitalization data were reviewed by an experienced physician and adjudicated as PTLD relevant; details on diagnoses and procedures performed during hospitalization were collected from the first diagnosis of PTLD to the earliest of the following: death, loss to follow up or end of study period (Sep 1st, 2018). We estimated the mean number of hospitalizations, average length of inpatient stay per admission and the percentages of time spent in the hospital out of the total time following PTLD index date or treatment failure index date. The PTLD index date was defined as the first date of EBV+PTLD diagnosis; and the treatment failure index date was defined as the earliest date of pts who became refractory or relapsed to first-line therapy of rituximab or rituximab plus CT. Results: A total of 35 EBV+PTLD pts were analyzed. All had failed first line rituximab monotherapy. Median follow up time was 24.8 months from the PTLD index date. Median age at PTLD diagnosis was 47 years (range 18-75). Of these, 6 (17.1%) were polymorphic, 21 (60%) were diffuse large B cell lymphoma, 3 (8.6%) were Burkitt lymphoma, and 5 (14.3%) were other B-cell lymphoma. Among the 35 pts, 23 (65.7%) died: 12 from PTLD, 6 treatment-related, 1 from organ failure, and 4 from other causes. The vast majority of pts (29 out of 35) received CHOP-based CT following rituximab failure (2 other CT, 4 did not receive CT). All pts (100%) had at least one inpatient hospitalization after PTLD diagnosis and 16 (45.7%) pts had at least one ICU admission following PTLD index date. The mean number of PTLD hospitalizations following PTLD index date was 4 (SD 3.2, range 1-12) and the mean average length of stay per hospitalization was 23.8 days (SD 22.6, range 2-94). The mean proportion of time spent in the hospital out of total time at risk from PTLD index date was 20.5% (SD 27.6, range 0.1-100) with an average of 9.5% of time spent in the ICU setting during hospitalization stay (SD 22, range 0-99.5). The mean number of PTLD hospitalizations (n of pts=19) following first course CT failure index date was 2.1 (SD 1.9, range 0-7) and the mean average length of stay per hospitalization was 14.8 days (SD 8.6, range 6-31.6). The mean proportion of time spent in the hospital out of total time at risk from CT failure index date was 41.8% (SD 39.6, range 0-100) with an average of 26% time spent in the ICU setting (SD 39, range 0-100). Conclusions: This is the first study to quantify the hospitalization burden directly related to EBV+PTLD post-SOT in Germany. The results show that hospitalization burden in EBV+PTLD post-SOT pts failing first line rituximab monotherapy is substantial accounting for approximately 20% of patient's time after initial diagnosis of PTLD with around 10% spent in the ICU setting. This hospitalization burden is even higher and accounts for over 40% of time in pts after additional treatment failure to first CT with 26% spent in the ICU setting. Disclosures Zimmermann: Roche: Research Funding; Janssen: Other: Travel, accomodations expenses; Atara Biotherapeutics: Other: Travel, accomodations expenses, Research Funding; Celgene: Other: Travel, accomodations expenses. Xu:Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Zhang:Atara Biotherapeutics: Employment, Equity Ownership. Thirumalai:Atara Biotherapeutics: Employment. Watson:Atara Biotherapeutics: Employment, Equity Ownership. Trappe:Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress related travel support; Roche: Consultancy, Honoraria, Other: Congress related travel support, Research Funding; AbbVie: Consultancy, Other: Congress related travel support; Celgene: Other: Congress related travel support.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4256-4256 ◽  
Author(s):  
Jingbo Yu ◽  
Shreekant Parasuraman ◽  
Dilan Paranagama ◽  
Ahmad Naim ◽  
David Dubinski ◽  
...  

Abstract Background: Patients with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), report high symptom burden that may compromise activities of daily living and quality of life. Results from the MPN Landmark survey suggest that for gainfully employed patients, disease symptoms may impact work productivity or career opportunities. The objective of this study was to assess the effects of MPNs on employment status, work productivity, and daily activities of patients in the United States. Methods: Adult patients (18-70 years) diagnosed with MF, PV, or ET participated in an online survey conducted between April and July 2016. The survey asked about diagnosis, disease-related history, MPN-related symptoms, functional status, changes in employment status since diagnosis due to MPNs, and work productivity (assessed using the Work Productivity and Activity Impairment Specific Health Problem Questionnaire, WPAI-SHP V2). Descriptive statistics were used to report MPN-related symptoms, employment changes, and WPAI scores for patients with MPNs who were employed at diagnosis and currently. Results: A total of 595 patients (MF, n=148; PV, n=284; ET, n=163) completed the survey, with 387 (65.0%) employed full- or part-time at diagnosis (MF, n=90; PV, n=178; ET, n=119). Among patients who were employed at diagnosis, mean (SD) age was 54.3 (10.5) years, 70.0% were female, and 47.8% had a bachelor's degree or higher. Mean (SD) duration of disease was 6.4 (6.6) years. After diagnosis, almost half of the patients (49.9%) experienced ≥1 change in employment resulting from their MPN, one-third (34.1%) had ≥2 different types of changes, and almost one-quarter (22.7%) had ≥3 different types of changes (Table). Almost one-third of patients (31.3%) reported 'leaving a job' due to their condition, which was also the most common employment change. The mean (SD) time from diagnosis to first job change due to MPN disease was 2.4 (5.2) years. Among those currently employed, the mean percentage of overall effects on work productivity due to MPNs were 29.3% for work impairment (MF, 28.4%; PV, 30.0%; ET, 28.6%), 25.7% for impairment while at work (presenteeism; MF, 22.1%; PV, 26.5%; ET, 26.4%), and 6.4% for work time missed (absenteeism; MF, 9.4%; PV, 6.6%; ET, 4.9%). The mean (SD) number of hours of work missed per week was 2.0 (4.9). The mean percentage of daily activity impairment was 31.6% (MF, 32.1%; PV, 32.0%; ET, 30.8%). The effects of MPNs on work productivity and daily activities are similar to those reported by patients with other significant chronic conditions such as rheumatoid arthritis (work time missed, 19.1%; impairment while working, 24.0%; activity impairment; 33.3%; Bansback N, et al. Rheumatology. 2012;51:375-84). Conclusion: MPNs have a substantial negative impact on patients' employment status and work productivity. Half of the employed patients with MPNs surveyed had a change in employment status (eg, leaving job, medical disability leave, early retirement) due to their disease. Moreover, currently employed patients reported a meaningful loss in work productivity due to their MPNs. Disclosures Yu: Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Dubinski:Incyte Corporation: Employment, Equity Ownership. Bai:Incyte Corporation: Employment, Equity Ownership. Mesa:Novartis: Consultancy; Galena: Consultancy; Ariad: Consultancy; Incyte Corporation: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Celgene: Research Funding; CTI: Research Funding.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1792-1792 ◽  
Author(s):  
Kevin Doner ◽  
Ian W. Flinn ◽  
Brian K. Ulrich ◽  
Stephen J. Noga ◽  
Naveed M. Chowhan ◽  
...  

Abstract Abstract 1792 Background: With increasing knowledge of cancer pathogenesis and availability of target-specific novel agents, it is expected that therapy will be increasingly tailored to individual biology. This is particularly true in lymphoma because translational research has characterized the molecular basis of the clinical heterogeneity in major lymphoma types, and many new agents are in development. However, a major challenge for clinical studies of specific lymphoma patient subgroups is the real-time testing of patient material in a way that enables prospective targeted clinical trials. Here we describe early patient selection results from a phase 2 trial of newly diagnosed DLBCL that prospectively identifies and enrolls only patients with the non-GCB subtype for randomization to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with or without the proteasome inhibitor bortezomib (VELCADE®). The non-GCB subtype exhibits inferior outcome compared to the GCB subtype after therapy with either CHOP or R-CHOP. Both preclinical and clinical data suggest that inhibition by bortezomib of the nuclear factor-κB pathway, which is frequently activated in non-GCB tumors, specifically benefits these patients (Dunleavy K et al, Blood 2009). Methods: This multicenter phase 2 study is enrolling patients at academic centers (n=10), major hospitals (n=13), and community practices (n=32), providing insight that may be broadly informative with respect to both patient outcomes and future targeted trial design. Obstacles to non-GCB-specific patient selection in this setting include change in standard treatment practice for DLBCL, as well as the challenges of collecting a tumor sample, running the assay, and reporting the subtype in a timely manner. All clinical centers in this study have agreed to release diagnostic pathology blocks to a College of American Pathologists/Clinical Laboratory Improvement Amendments-certified pathology lab for centralized subtyping. The pathology samples are subject to non-GCB testing via a 3-marker immunohistochemistry panel (CD10, bcl-6, mum-1; Hans CP et al, Blood 2004), and the results are reported directly to the clinical site. Results: To date, 45 patients have provided consent and have been subtyped. The mean turnaround time from receipt of sample to reporting of subtype was 1.2 business days (range 1–2 business days). All pathology blocks have been returned to the clinical sites; the mean time elapsed was 4.6 business days (range 4–6 business days). Rapid return of these samples was cited by clinical centers as an important aspect of the study design. There is no indication that pathology block release and central laboratory subtyping has led to delays in patient treatment. Of the 42 patients with results available to date, 5 samples were inevaluable, primarily due to limited tumor cells in the biopsy. Of the 37 samples successfully subtyped, 22 were GCB (59.5%) and 15 were non-GCB (40.5%); this is generally consistent with the ∼50% prevalence of the non-GCB subtype reported in retrospective studies of DLBCL. Fourteen patients have been randomized to therapy. Conclusions: Updates to turnaround time, patient subtype frequency, and enrollment will be presented. These data indicate that many centers are interested in targeted trials that offer new and potentially tailored therapies for their DLBCL patients. These centers can overcome their reluctance to release diagnostic pathology samples and actively enroll patients to randomized studies of frontline therapy. Overall, these results suggest that with careful trial design and attention to key logistical issues, prospective enrichment of specific patient subtypes is feasible in lymphoma. The PYRAMID trial (Clinicaltrials.gov: NCT00931918) continues to enroll patients. Disclosures: Off Label Use: Discussion of Velcade in NHL subtypes other than mantle cell lymphoma is included. Flinn:Millennium Pharmaceuticals, Inc: Research Funding. Noga:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cephalon: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ortho-Centicor: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Papish:Genentech: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Consultancy; MD Advantage: Consultancy; Genomic Health: Speakers Bureau. Reeves:Celgene: Equity Ownership. Parasuraman:Millennium: Employment, Equity Ownership. Corvez:Millennium: Employment, Equity Ownership. Mulligan:Millennium Pharmaceuticals, Inc.: Employment. Leonard:Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1080-1080
Author(s):  
Howard Liebman ◽  
James B Bussel ◽  
Mansoor N Saleh ◽  
Heather Horne ◽  
William A Wegener ◽  
...  

Abstract Background As a 2nd-generation humanized anti-CD20 monoclonal antibody, veltuzumab has structure-function differences from rituximab and has shown increased potency in comparative preclinical studies (Goldenberg et al., Blood. 113(5):1062-70, 2008). In non-Hodgkin lymphoma (NHL), subcutaneous (SC) injections of low-dose veltuzumab using a high-concentration formulation demonstrated activity (Negrea et al., Haematologica. 96:567-73, 2011) comparable to that achieved previously by intravenous infusions (Morschhauser et al., J Clin Oncol. 27:3346-53, 2009). The prospect of SC veltuzumab for treating autoimmune diseases is particularly attractive. We present final phase I results from a multicenter study comparing two dosing schedules of low-dose SC veltuzumab administered as a monotherapy in immune thrombocytopenia (ITP). Methods Adults with primary ITP who failed ≥1 standard therapy were eligible if platelets were ≤30 K/μL without major bleeding. In Cohort 1, 80, 160, or 320 mg SC veltuzumab doses were given twice, 2 weeks apart (total dose 160, 320, 640 mg, respectively). All patients in Cohort 2 received once-weekly 320 mg doses for 4 weeks (total dose 1280 mg). Steroids or other premedications were not required. An objective response (OR, ≥30 K/μL platelets twice, one week apart, and at least doubled from baseline) was classified as complete (CR) if ≥100K μL, otherwise as partial (PR). For responders, time to relapse (TTR) was measured from first injection to relapse with platelets below 30K/μL, initiation of subsequent treatment, or lost to follow-up. Adverse events (AEs) and safety laboratories were evaluated by NCI CTC v3 toxicity grades. Other evaluations included circulating B-cell levels (CD19), veltuzumab serum levels, and human anti-veltuzumab antibody (HAHA) titers. Results A total of 50 patients (31 female/19 male, median 54-years old, 8 post splenectomy) were enrolled in Cohorts 1 (N=34) and 2 (N=18, including 2 rollovers). They were a median of 2 years from diagnosis of ITP; 14 patients had newly-diagnosed or persistent disease (ITP ≤ 1 year) treated with corticosteroids and/or immunoglobulins, and 36 patients had chronic disease (ITP > 1 year) and also had received azathioprine or danazol (N=15), thrombopoietin-receptor agonists (N=10), rituximab (n=7), platelets (N=5) or chemotherapy (N=4). SC veltuzumab was well tolerated with a limited number of AEs (all Grade 1-2 transient injection reactions) and no other safety issues. At all doses, B cells were depleted rapidly after the first administration of veltuzumab, with recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with each injection, achieving mean Cmax values of 11.7, 19.3 and 40.6 µg/mL at dose levels of 80, 160, and 320 mg, respectively, in Cohort 1, and 67.0 µg/mL at 320 mg in Cohort 2. HAHA titers were positive in 7 patients; interestingly, 4 had ORs, including 3 CRs. Three patients given rescue medication for rapidly decreasing platelets at study entry were inevaluable for treatment response. Of 47 evaluable patients, 22 (47%) had ORs, including 13 (28%) CRs, which differed little with ITP duration (≤1 year: 51% OR, 29% CR; >1 year: 42% OR, 27% CR). For responders, median TTR was comparable for CRs and PRs (7.9 vs 7.6 months, respectively) but decreased with ITP duration (14.4 vs 6.9 mo. for ≤1 year vs >1 year, respectively). OR and PR rates tabulated below for each dose group show meaningful activity (including CRs) already achieved at the lowest dose level, with no evidence of dose-dependent response rates, although response duration appears increased with higher total doses delivered. Conclusions Low-dose SC veltuzumab was convenient, well-tolerated, with good B-cell depletion and therapeutic activity across all dose levels and with comparable outcome when administered as 2 doses, 2 weeks apart, or as 4 consecutive weekly doses. These results support further studies in ITP combining SC veltuzumab with other agents or given as a maintenance regimen. Disclosures: Liebman: Immunomedics: Research Funding. Off Label Use: Veltuzumab is investigational agent for treatment of ITP. Bussel:Immunomedics: Research Funding. Saleh:Immunomedics: Research Funding. Horne:Immunomedics: Employment, Equity Ownership. Wegener:Immunomedics: Employment, Equity Ownership. Goldenberg:Immunomedics: Employment, Equity Ownership.


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