bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy with Interleukin-2 Versus Observation for Patients with Non-Hodgkin’s Lymphoma: Results of a Phase III Randomized Trial by the Southwest Oncology Group (SWOG 9438).
Authors: Thompson John A. , Fisher Richard I. , LeBlanc Michael L. , Unger Joseph M. , Forman Stephen J. , Stiff Patrick J. , Fefer Alexander 
Published: October 2019

Abstract
Purpose: To determine the effect of post-transplant immunotherapy with Interleukin-2 (IL-2) on the progression-free and overall survival of patients with non-Hodgkin’s lymphoma (NHL) after autologous stem cell transplantation and to assess the toxicity of post-transplant IL-2 therapy.
Patients and Methods: Patients with previously treated low, intermediate, or high grade NHL (except Working Formulation Groups A and I) were treated with high-dose cyclophosphamide, etoposide, and total body irradiation (TBI) and an autologous peripheral blood stem cell transplant (PBSCT). Twenty-eight to 80 days after PBSCT, patients were randomized to treatment with IL-2 versus observation.
Results: Between January 1995 and July 2004, three hundred ninety-four patients with low-grade (n=61) or intermediate-high grade NHL (n=315) were registered at one of 39 SWOG transplant centers. One hundred ninety patients did not proceed to randomization, because of patient refusal (44), grade V toxicity (30), disease progression (28), toxicity (28), or other reasons. Two hundred four patients were randomized to treatment with continuous infusion intravenous IL-2 (9 ×106 units/m2/day for four days followed five days later by 1.6 ×106 units/m2/day for 10 days) versus observation. The 4-year progression-free survival estimate for all eligible patients is 34%, and the 4-year overall survival estimate is 52%. There was no difference in progression-free survival (hazard ratio (HR) of IL-2 to observation = 0.90; p = 0.56) nor in overall survival (HR of IL-2 to observation = 0.88; p = 0.55). There were no deaths related to IL-2 treatment. Grade IV IL-2-related toxicities included hematologic (n=10), cardiovascular (4), renal/bladder (2), flu-like symptoms (1), lung (1), metabolic (1), and neurologic (1) and were reversible in all cases.
Conclusions: These results confirm earlier SWOG findings that a regimen of cylophosphamide, etoposide and TBI followed by PBSCT can be administered to patients with relapsed or refractory NHL with acceptable toxicity and with encouraging progression-free and overall survival. Post-transplant therapy with IL-2 given at this dose and schedule of administration had no significant effect on post-transplant relapse, progression-free survival or overall survival.
Rituximab (Mabthera) Improves the Treatment Results of DHAP-VIM-DHAP and ASCT in Relapsed/Progressive Aggressive CD20+ NHL. A Prospective Randomized HOVON Trial.
Authors: Vellenga Edo , Notenboom Annelise , van ‘t Veer Mars , Zijlstra Josée , Fibbe Willem E. , van Oers Rien , van Imhoff Gustaaf W. , Lugtenburg Elly , Huijgens P.C. 
Published: October 2019

Abstract
A total of 239 patients with relapsed/progressive aggressive CD20+ NHL after/during adriamycin containing regimens, were recruited to the randomized HOVON-44 trial comparing DHAP-VIM-DHAP followed by BEAM and autologous stem cell re-infusion (ASCT)(“DHAP-arm”) with DHAP-VIM-DHAP in conjunction with Rituximab (375 mg/m2) and ASCT (“R-DHAP arm”). Of the included patients, 202 were evaluable and randomized to the DHAP arm (n=101) or R-DHAP arm (n=101). Only patients with CR/PR after two courses of intensive chemotherapy were eligible for ASCT. Patients were well balanced for risk factors. In both arms the majority of patients had not been exposed to Rituximab during first line treatment. As of July 2006, median follow-up of all patients still alive is 24.5 months. After two courses of chemotherapy PR/CR was obtained in 49 % of the patients in the DHAP arm and 77% in the R-DHAP arm (p=<.01;intention to treat analysis). Post-transplantation PR/CR was obtained in 41% and 58% of the patients respectively (p=.40). A significant difference between both arms was observed for failure free survival (FFS), disease free survival (DFS) and overall survival (OS) in favor of the Rituximab arm (p<.05, table 1). The less pronounced difference in OS between both arms is most likely due to the fact that non-responding or relapsing patients in the DHAP arm received salvage treatment with a Rituximab containing regimen. Additionally, a subgroup analysis was performed according to type of response to first-line treatment:1) Response duration more than 3 months (n=138); 2) Progression or response duration less than 3 months (n=64). Within both subgroups, the hazard ratio’s for the endpoints were of equal magnitude (.40–.60), indicating that the beneficial effect of Rituximab existed in both subgroups. In conclusion these results demonstrate that the addition of Rituximab to second line of chemotherapy followed by ASCT results in a significant improved FFS, DFS, and OS in patients with relapsed/progressive aggressive CD20+ NHL.
Table 1 FFS DFS OS *: 2 years estimate DHAP-arm* 21% 46% 48% R-DHAP arm* 52% 82% 62% Hazard ratio .40 .32 .61 p-value log rank test <0.001 0.003 0.03
Content, Accuracy and Quality of Warfarin Patient Information.
Authors: Geerts William H. , Diamantouros Artemis , Bartle Bill , Kim Linda , Selby Rita 
Published: October 2019

Abstract
Background: Warfarin is a very common, narrow therapeutic index drug which requires clear understanding by patients in order to ensure its safe use. Patients are largely educated about warfarin through written information sheets provided by pharmacies. It is critical that these sheets provide all of the essential information about warfarin use in a format that is accurate and understandable.
Objective: The goals of this study were to assess the content and accuracy of warfarin information sheets provided to patients by community pharmacies as well as to assess the reading level of each information sheet.
Methods: A reference standard for warfarin patient information was developed, based on a formal survey of a national group of thrombosis health professionals. Warfarin patient information sheets, distributed by community pharmacies, were compared to the reference standard. Reading level was assessed using two standardized instruments, the Flesch-Kincaid scale and SMOG scale, and compared to the recommended Grade 5 to 6 level for patient information sheets. Patient information booklets, distributed by the producers of warfarin, were also evaluated.
Results: Six different warfarin patient information sheets were distributed by 98% of the community pharmacies in Ontario. On average, these sheets included only 44% of the recommended essential or important knowledge items (range 20–52%), with considerable variability in the content of specific items. Each sheet also contained incorrect information. The average reading level of the information sheets was Grade 11 (range Grade 7 to above Grade 12). On average, the pharmaceutical booklets included 71% of the essential or important information items (range 58–84%).
Conclusions: Patients prescribed warfarin are likely to receive information sheets from a community pharmacy that contain less than half of the information content important to their safe use of warfarin as well as statements that are misleading or incorrect. Furthermore, comprehension of these sheets is limited by a reading level substantially higher than recommended. All six of the information sheets reviewed were derived from an American drug information database and therefore, generalized applicability of these results exists. The information that patients receive about warfarin must be improved and we suggest that a national standard be used.
Cost-Minimization Analysis of Anti-D Immune Globulin Versus Intravenous Immune Globulin for the Initial Treatment of Immune Thrombocytopenic Purpura.
Authors: Wetzel David A. , Tarantino Michael D. 
Published: October 2019

Abstract
Immune Thrombocytopenic Purpura (ITP) is an autoimmune disorder in which opsonized platelets are prematurely destroyed within the spleen. At this time both anti-D immune globulin (anti-D) and intravenous immune globulin (IVIG) are established treatment options for the management of ITP in children and adults. Due to the tremendous increase in demand for IVIG products in the past decade and the subsequent lack of sufficient production a national shortage has emerged. As a consequence, the direct cost and resulting burden on the healthcare payer has risen dramatically for this treatment option. We performed a cost-minimization analysis (CMA) to compare the cost of using anti-D versus IVIG for the initial treatment of non emergent ITP in appropriate patients. A CMA was employed for this economic evaluation because clinical evidence supports the supposition that the efficacies of the treatment options in question are similar. The perspective used for this study was that of the healthcare payer. The study population includes children and adults with non emergent forms of ITP who are both Rh positive and nonsplenectomized. This CMA did not include the cost to the healthcare payer for treatment administration or the incidence and cost of subsequent treatments for each product. The incidence of severe adverse events when using IVIG or anti-D are rare and therefore were not included in this CMA. In this analysis the cost for the non emergent initial treatment of ITP using [Immune Globulin Intravenous (Human)] 10% (Gammagard Liquid 10%) 1gm/kg × 2 days was compared to anti-D (WinRho® SDF Liquid) 50μg/kg × 1 day respectively. We performed a CMA using the same initial dose and duration of IVIG and anti-D dosed at 75μg/kg. And finally we performed a CMA using one day of treatment for both IVIG and anti-D dosed at 75μg/kg. An average patient weight of 75kg was used for initial dose calculations for each product. The average wholesale price (AWP) for each product was used for cost calculations. Gammagard Liquid 10% was selected as the product for IVIG therapy because this product currently holds a large portion of market share for IVIG products in the US. An example CMA calculation was; Gammagard Liquid 10% 1g/kg × 75kg × 2 days × $101.25 – WinRho® SDF 50μg/kg × 75kg × $1.10/μg. The results of these three CMAs when using anti-D versus IVIG for the initial treatment of ITP yielded a cost savings of $11,063.00, $9,000.50 and $1,406.25 respectively. When the CMA calculations were adjusted to use the actual number of vials needed to dispense the final dose of IVIG and anti-D dosed at 75μg/kg, the savings realized was $1,213.75 per dose dispensed. These CMAs have demonstrated the cost benefit of using anti-D for the initial treatment of non emergent ITP in appropriate patients.
Cost-Effectiveness of Posaconazole Versus Standard Azole Therapy in the Prevention of Invasive Fungal Infections among High-Risk Neutropenic Patients in the U.S.
Authors: O’Sullivan Amy K. , Pandya Ankur , Thompson David , Papadopoulos George , Weinstein Milton C. , Perfect John R. , Langston Amelia 
Published: October 2019

Abstract
In a recent clinical trial, posaconazole was found to be superior to standard azole therapy (i.e., fluconazole or itraconazole) in preventing both invasive fungal infections (IFIs) and in reducing overall mortality among high-risk neutropenic patients. We conducted a cost-effectiveness analysis based on trial results from a U.S. perspective. A decision-analytic model was developed to estimate the cost-effectiveness of antifungal prophylaxis among patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) at high risk of developing an IFI due to chemotherapy-induced neutropenia. To extrapolate trial results to a lifetime horizon, the model was extended with one-month Markov cycles in which mortality risk is specific to the underlying disease as estimated from SEER data. Patients in the model were assumed to receive prophylaxis with posaconazole or standard azole therapy (fluconazole, 81%; itraconazole, 19%). The probabilities of experiencing an IFI, IFI-related death, and death from other causes over 100 days of follow-up were estimated from the trial data. Long-term mortality, drug costs, and IFI treatment costs were estimated using published sources. The model was used to estimate costs, IFIs avoided, life-years gained, and the incremental cost-effectiveness of posaconazole versus standard azole therapy (using 2006 dollars). Posaconazole is associated with fewer IFIs (0.05 vs. 0.11), increased life years (0.744 vs. 0.728), and (excluding costs of the underlying condition) slightly lower costs ($4,887 vs. $5,070) per patient relative to standard azole therapy over a lifetime horizon. One-way sensitivity analyses indicate that when model parameters are varied across reasonable ranges of their base-case values, the incremental cost-effectiveness ratio for posaconazole ranges from cost saving to $50,000 per life-year saved relative to standard azole therapy. A second-order probabilistic Monte Carlo sensitivity analysis was conducted to assess the effects of parameter uncertainty on the study findings, particularly as relates to treatment efficacy and the costs of an IFI. Results indicate that there is a 75% probability that posaconazole is cost saving versus standard azole therapy and a 90% probability that the incremental cost-effectiveness ratio for posaconazole is at or below the $50,000 per life year saved threshold. Posaconazole has been shown to be more effective than standard azole therapy (i.e., fluconazole or itraconazole) in preventing IFIs and reducing overall mortality in high-risk neutropenic patients.
Based on this analysis, we conclude that posaconazole is likely to be cost saving relative to standard azole therapy (i.e., fluconazole or itraconazole) in the prevention of IFIs among high-risk neutropenic patients.
Chemotherapy-Related Amenorrhea (CRA) among Premenopausal Patients Treated for Acute Leukemia.
Authors: Fanning Suzanne R. , Jin Tao , Hilden Joanne M. , Advani Anjali , Kalaycio Matt , Lichtin Alan E. , Sekeres Mikkael A. , Sobecks Ronald , Moore Halle C.F. 
Published: October 2019

Abstract
Background: Little is known about the late effects of treatment for acute leukemia on ovarian function. We sought to evaluate the rate of long-term chemotherapy-related amenorrhea (CRA) among premenopausal women treated for acute leukemia.
Methods: The Cleveland Clinic database of patients treated for acute leukemia between July 1994 and July 2005 was searched for patients aged 15–44 at diagnosis who were believed to be alive. Thirty of 69 identified patients were excluded due to active disease, on-going treatment or lost to follow-up. Questionnaires regarding menstrual and fertility history were mailed to the remaining 39 patients.
Results: Twenty-five patients responded to the questionnaire, 4 of whom were excluded due to lack of menses at the time of diagnosis (n=2), use of Depo-provera at time of diagnosis (n=1) or use of Depo-provera at time of f/u (n=1). The median age of the remaining 21 patients was 30 (range 15 to 44). Thirteen patients had AML and 8 had ALL. Nine of the 21 had undergone myeloablative transplant, 8 allogeneic and 1 autologous. Median f/u time from treatment was approximately 43 months (range 9 to 141). Long-term CRA occurred in 8/21 patients (38%). Only 2/12 patients (17%) who received standard-dose chemotherapy alone had persistent CRA while 6/9 (67%) of those undergoing transplant had persistent CRA (p=0.032, Fisher’s Exact test). The incidence of CRA increased with age: 0/3 patients under age 18, 1/4 patients age 18–25, and 7/14 patients age 26–44 at treatment remained amenorrheic (p=0.042, 1-sided Cochran-Armitage test). Only 2 patients reported attempts at fertility following treatment. One patient reported delivering three children, the other patient was amenorrheic and was undergoing fertility treatment.
Conclusions: These findings suggest that a substantial minority of young survivors of acute leukemia will experience premature ovarian failure. Increasing age at treatment and transplant are associated with a greater risk of long-term CRA.
Invasive Streptococcus Pneumoniae Infections in Pediatric Cancer Patients: High Morbidity and Mortality with Several Vaccine Failures.
Authors: Weber Lynn , Allen Charlet A. , Ackerman Patricia , Messinger Yoav 
Published: October 2019

Abstract
Invasive pneumococcal infections can be devastating in the setting of immune deficiency. These infections have been seen in pediatric oncology practices, but the outcome has not been reported. With the introduction of routine 7- valent pneumococcal conjugate vaccine (PCV7) the rate of pneumococcal infections dramatically decreased in the general pediatric population. It is unclear if a similar reduction in rate would be seen in pediatric oncology patients. A total of 44 pneumococcal infections occurred in 34 oncology patients at Childrens Hospital and Clinics of Minnesota over a 5-year period (5/1/2001 – 4/30/2006). Twenty-five episodes of invasive infection were identified in 24 patients, of which 4 (16.7%) required intensive care admissions and 2 of them died (8.3%). During this period 863 new malignancies were diagnosed, therefore our rate of invasive infection is estimated to be 28 per 1000 oncology patients. This is higher than the reported rate of 3.8 8.1 infections per 1000 stem cell transplantation patients. Fifteen patients (62%) with invasive infections were diagnosed with leukemia, of which 12 had acute lymphoblastic leukemia. The invasive infections occurred a median of 15.2 months (range 0–36) after diagnosis and the median patient age at time of infection was 5.6 years (range 1.5 - 14). The average length of hospitalization for patients was 8.3 days (range 0–38), with six patients receiving outpatient therapy alone. Pneumococcal serotypes were known in 21 of the 25 episodes of invasive pneumococcal infection and in 1 non-invasive infection. Of the 22 serotypes identified, 19 were covered by either PCV7 or the 23-valent pneumococcal polysaccharide vaccine (PS23). Eleven patients who were immunized with either PCV7 or PS23 later developed a pneumococcal strain that should have been covered by the immunization. Three patients who received immunization acquired a strain of streptococcus pneumoniae not included in either vaccine. Invasive pneumococcal infection is a potentially preventable complication with a high morbidity and mortality. Use of PCV7 or PS23 may not prevent the development of pneumococcal infection in pediatric oncology patients with vaccine-susceptible strains. It is unclear whether immunization before and during the immunocompromised period results in protective immunity against streptococcus pneumoniae.
Low Dose Liposomal Amphotericin B (L-AmB) as Prophylaxis of Invasive Fungal Infections (IFI) in Neutropenic Patients (pts): Is It Cost Effective?.
Authors: Penack Olaf , Martus Peter , Thiel Eckhard , Blau Igor W. 
Published: October 2019

Abstract
Background In a recently reported randomized trial (ASH meeting 2005, oral presentation #1310) low-dose intravenous L-AmB reduced the incidence of IFI (20.2% vs. 4.6%, p<0.001) in high risk pts with hematological malignancies and prolonged neutropenia. The purpose of the current study was to compare the pharmacoeconomics of L-AmB prophylaxis vs. no systemic antifungal prophylaxis.
Methods: Records of all randomized pts with acute leukemia were reviewed for dosage and duration of antimycotic and antibiotic treatment during hospital stay. Based on this data and current drug prices the mean costs of antimicrobial treatment (AT) per hospital stay were calculated.
Results Pt. characteristics: Randomized pts 132; eligible pts 100; arm A: 56 (L-AmB prophylaxis); arm B: 44 (no prophylaxis). Baseline characteristics were balanced for age (mean 55.8 years), underlying disease (81 AML, 19 ALL) and duration of neutropenia (mean 18.5 days). Endpoints: The costs for antifungal treatment (excluding prophylaxis) were 360 Euro in arm A vs. 2170 Euro in arm B (p<0.001). Expenditures for antifungal prophylaxis accounted for 630 Euro in arm A vs. 0 Euro in arm B. The costs of antibiotic treatment were lower in arm A compared to arm B (210 Euro vs. 670 Euro, p<0.001). The total costs for AT (including antifungal prophylaxis) per hospital stay were 1200 Euro in arm A vs. 2840 Euro in arm B (p=0.071).
Conclusion: Our results suggest that antifungal prophylaxis with low dose L-AmB in high risk patients with hematologic malignancies has the potential to reduce the incidence of IFI and may be a cost-saving strategy.
Inadvertent Intrathecal Administration of Vincristine.
Authors: Basetty Praveena , Buffie Charlie G. , Lagman Jennifer , Tigue Cara C. , Dandade Neal , Bennett Charles L. 
Published: October 2019

Abstract
Background: Vincristine is a vesicant drug which is normally given intravenously. Intrathecal administration of vincristine is a therapeutic misadventure, causing chemical leptomeningitis and focal ventriculitis. While 55 cases of intrathecal vincristine administration have been reported worldwide, only 32 cases have been documented in the literature, 13 have been reported to the FDA Med Watch, and many more cases are believed to be unreported. Of the documented cases, 84.3% resulted in death and 15.6% of those who survived had serious neurological consequences such as quadriplegia and paraplegia.
Methods: The Research on Adverse Events and Reports (RADAR) project conducted a review of literature published between 1968 and June 2006. Sources included Med Watch reports, published abstracts and journal articles, online newsletters, and letters from pharmacists.
Findings: The reports reviewed showed that intrathecal administration of vincristine occurred most often because of inadequate communication between pharmacy and medical staff (22 of 32 cases; 68.7%). In these cases, the pharmacy mistakenly delivered vincristine syringes together with syringes containing intrathecal medications and physicians or nurses wrongly administered vincristine intrathecally. Pharmacy error alone, such as the mislabeling of syringes, accounted for 6 of 32 cases of intrathecal administration of vincristine (18.7%) while physician/nurse error alone (failure to read syringe labeling or check physician’s orders) accounted for 4 of 32 cases (12.5%).
Conclusions: Since vincristine is lethal when given intrathecally, its administration should be executed with the precautionary measures employed with other potentially lethal substances, such as blood products. Carefully reviewing physician orders before drug administration and dispensing vincristine in syringes incompatible with spinal needles can also curb fatal error. Other preventive measures include properly labeling vincristine syringes for intravenous use only and diluting vincristine in intravenous mini-infusion bags.
Literature review of case reports since 1968 < 1985 1986–1990 1991–1995 1996–2000 2001–2005 Total USA/Canada 7 1 2 4 2 16 Europe 0 0 2 2 1 5 Australia 0 1 1 0 1 3 Asia 1 0 1 3 0 5 Total Cases 8 2 6 8 8 32 Deaths 8 1 4 6 8 27 (84.3%) Pharmacy/medical staff error 5 1 3 5 5 22 (68.7%) Pharmacy error 2 0 2 2 3 6 (18.7%) Physician/Nurse error 1 1 1 1 0 4 (12.5%)