bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between real costs and patient's perceptions of the chemotherapy in a Brazilian cancer care facility.
Authors: Lorandi Vinicius , Debiasi Marcio , Stefani Stephen D. , Ribeiro Leticia , da Costa Marieni , Trevisan Bibiana 
Published: September 2018

e18343 Background: Cancer is growing very fast and is responsible for roughly 7 million deaths annually. Cancer patients throughout the world suffer from both psychosocial and financial distress early in the time they are diagnosed with the disease. While anti-cancer therapy can magnify such effects by consuming extra intellectual energy from the patient and their family, further burden derived from the economic implications of cancer treatment have been ranked by many as an urgent issue. Methods: 46 patients with diagnosis of prostate, breast, lung or gastrintestinal cancer were asked to fill out a form while receiving chemotherapy. It contained 14 questions. Nurses were responsible for data collection. Wilcoxon test was used to test for interaction. Results: The mean age of patients was 62.2 (±13) and 58% of them were women. Aproximately half of them declared having completed higher education or more. The majority of patients had breast cancer (40%) followed by colorectal (38%), prostate (16%) and lung (5%). Most of the patients believed to be treating a localized disease and thought cure was their treatment goal. 31% of patients said they spent more than expected with their treatment and nearly half thought cost to be a concern. When reviewing patient's expectations and real treatment goals we noticed that the majority of patients had stage IV disease (56%) and that 60% were under palliative care. The median actual cost declared by patients was R$3,000 while the real cost median was R$7,055 which accounts for a 40% downstaging of the real cost. At last, 78% of patients estimated the costs to be less than it really is. Conclusions: There is still a large gap between patient's perceptions about chemotherapy goals and disease stage. When it comes to costs of the treatment the majority of patients tend to underestimate it. That may be in part because most brazilian private health care providers do not work with co-participation and therefore all costs are covered.
Effect of clinical outcome-driven reimburesement on cost savings and innovation in multiple myeloma.
Authors: Oren Ohad , Oren Michal 
Published: September 2018

e18344 Background: The cost of cancer care is dissociated from the individual patient’s clinical outcome. A cancer patient treated with a particular drug incurs a fixed expense that is independent of her clinical response. Manufacturers thus have little incentive to design medications more effective than the minimum required for FDA approval. Methods: We propose a model whereby drug manufacturers are rewarded for sustained patient responses. Clinical information flowing to insurance companies dictates patients’ co-payment rates. “Integrated” PFS (iPFS) is defined as the mean of the median PFS of all medications approved for an indication. Patients with objective evidence of disease progression before reaching a given iPFS endure no out-of-pocket expenditure and insurance company deducts a certain percentage from launch price. Patients with durable responses longer than a chosen iPFS threshold pay 20% while the insurance company pays 80% of launch price. For each patient still responding at a specific (high) iPFS, drug company earns extra percentage of launch price via the insurance company (same fraction saved from cases of failure to respond). PFS Kaplan-Meier curves of five common drugs in mm were assessed. Model's impact was calculated. Results: The calculated iPFS was 17 months. iPFS thresholds chosen were 0.7 and 1.2, equaling 11.9 and 20.4 months. For each patient progressing before 11.9 months, the manufacturer were to (randomly) lose 19% of launch price. For each patient with no progression at 20.4 months, it was calculated that manufacturers should earn extra 15% of launch price to achieve overall financial neutrality. Patients had no out-of-pocket expenditure if they had progression earlier than 0.35 iPFS. Approximately 70k patients experienced early progression and were spared cost, with savings amounting 5 m dollars. Amgen and Bristol-Myers generated extra annual revenues amounting 18.4 and 10.6 m dollars for carfilzomib and elotuzumab. Celegne and Takeda experienced annual deductions of 9.9 and 25.9 m dollars for lenalidomide and bortezomib. Conclusions: Our model would spur scientific innovation while generating economic savings for mm patients.
Frequency of target attainment and toxicity with reduced PEG-asparaginase (PEG) dosing in acute lymphoblastic leukemia (ALL).
Authors: Streck Mitchell , Christ Trevor , Stock Wendy , Knoebel Randall 
Published: September 2018

e18501 Background: Asparaginase (ASN) is a critical part of ALL therapy; however, in adults, a higher incidence of toxicities results in treatment delays and suboptimal exposure. We have reported a higher rate of PEG toxicity in pts > 50 yrs of age, baseline liver dysfunction, diabetes, and obesity (BMI ≥ 30). Thus, we hypothesized that reducing the PEG dose from 2500 units/m2 to 1000 units/m2 with further reduction to 500 units/m2 if any of those co-morbidities were present would reduce toxicities and still achieve therapeutic ASN levels. Methods: This is a single-center, retrospective study that included adult pts with ALL. Pts must have received at least one dose of PEG using a pediatric inspired regimen that includes 7 doses of PEG. The primary objective was to determine the rate of target ASN activity (≥ 0.1 IU/mL) one week after administration of reduced PEG during induction. Secondary objectives included the incidence of grade 3/4 toxicity based upon CTACE 4 criteria (hepatotoxicity, pancreatitis, hypertriglyceridemia, and VTE) between standard (SD) > 1000 units/m2 and reduced (RED) ≤1000 units/m2 PEG dosing. Results: 41 consecutive pts with ALL were included. Median age was 43 years (range 18-76). Median WBC upon admission was 7.6. At baseline, 25 pts (61%) had at least one comorbidity. 26 pts (63%) received SD PEG and 15 pts (37%) received RED PEG with median dose 1000 units/m2. 80% of pts achieved target ASN activity following administration of a RED PEG induction dose, median level of 0.1 IU/mL (IQR 0.1-0.24 IU/mL). 30 pts (73%) experienced grade 3/4 toxicity during induction, 81% in the SD group vs 60% in the RED group (p = 0.3). During induction, grade 3/4 hepatotoxicity was seen in 16 SD pts (62%) vs 6 RED pts (40%) (p = 0.211). Grade 3/4 hyperbilirubinemia was seen in 12 SD pts (46%) vs 1 RED pt (7%) (p = 0.014). Conclusions: The majority of pts attained a therapeutic ASN activity level with RED PEG. This resulted in a trend towards lower incidence of overall toxicity and a significant decrease in hyperbilirubinemia. A larger prospective study will be needed to determine whether decreased toxicity during induction correlates with fewer treatment delays, improved drug delivery, and better treatment outcome.
Cost of care for adult patients with relapsed acute lymphoblastic leukemia (rALL) in Germany.
Authors: Su Yun , Schmitter Sarah , Navarro Ana , Mayerhoff Lukas , Prieur Sigurd , Lehne Moritz , Loberiza Fausto Rodriguez 
Published: September 2018

e18504 Background: Adult ALL is a rare but progressive frequently fatal disease. For those who survive and respond to initial therapy, many experience relapse. For relapse ALL (rALL), stem cell transplant (SCT) is potentially curative. This retrospective observational study investigates the cost of care and the impact of SCT on total cost for rALL. Methods: A representative sample of German claims data covering approximately 7 million of the German population was used to identify patients 18 years and older with a new diagnosis of ALL (ICD-10-GM code: C91.0*) between Jan 2011 and Dec 2015 who had a relapse after remission to initial treatment. Mean health care cost per patient per quarter were determined by whether or not SCT was received after relapse. Costs were from the perspective of German statutory health insurance and included prescription, outpatient and inpatient treatment costs. Results: Of the total 116 incident adult ALL patients identified, 29 (25%) were determined to have had a relapse, 11 underwent SCT after the relapse (38%). Patients with a SCT appear to incur higher cost than those without SCT in each of the quarters after relapse was diagnosed (Table), with the highest in the first quarter, but decreasing in subsequent quarters. Inpatient cost accounted for the majority of the cost for the first three quarters for both SCT and non-SCT patients (64% in Q2 to 86% in Q1). The number of patients in the SCT cohort remained relatively stable, while the non-SCT cohort had only half the patients left by the third quarter post relapse. Conclusions: Current results inform the magnitude of cost in Germany associated with adult patients with rALL with or without a SCT after relapse. It would be important to determine the magnitude of benefit such as long-term survival associated with SCT as well. The cost estimates provide a benchmark against which new treatment options for rALL can be compared. [Table: see text]
Efficacy of clofarabine and low-dose cytarabine combination for genetically high-risk acute myeloid leukemia prior to allogeneic stem cell transplantation.
Authors: Vigil Carlos Enrique , Jahan Nusrat , Paun Oana Valeria , Weis Jennifer , Heckman Kevin , De Magalhaes-Silverman Margarida , Carter Thomas H. 
Published: September 2018

e18515 Background: The outcome of genetically high risk acute myeloid leukemia (AML) patients (pts) remains poor, with a median overall survival (OS) of a few months after the failure of regimens. Long-term survival requires complete remission followed by allogeneic stem cell transplantation (ASCT).Clofarabine, a deoxyadenosine analog, at 20mg/m2 days 1-5, in combination with low-dose cytarabine (LDAC) has reported efficacy and tolerability in older newly diagnosed AML pts (Cancer 2015;121:2375). We have therefore prioritized this combination for relapsed/refractory(R/R) pts. Aims:Determine the efficacy of Clofarabine and low dose cytarabine in R/R AML pts who are eligible for ASCT. Methods: Using Holden Comprehensive Cancer Center database, we performed a retrospective chart review on 16 pts of R/R AML who were treated with Clofarabine and LDAC between January 2014 and Dec 2016. Each patient received Clofarabine 20mg/m2on days 1-5 IV and LDAC on days 1-10 subcutaneous. The primary endpoint was complete remission (CR) or complete remission with incomplete marrow recovery (CRi). Secondary endpoint was median OS. Results: Sixteen pts were analyzed. The median age was 58 years (range 27-78). Nine pts (56%) had AML with high risk characteristics (complex karyotype and/or presence of FLT3-ITD). Nine pts achieved either a CR or CRi. Responses were observed in 7of 9 pts with genetically high-risk features. 2 pts had mutated TP53, and both of them achieved CR. The median OS time was 13.25 months (range 3.6-19.2 months). 4 pts received ASCT after treatment combination. Conclusions: These results suggest that Clofarabine is well-tolerated and effective in the treatment of R/R AML pts, especially those with high-risk genetics. Clofarabine and LDAC could be used as a bridging therapy prior to ASCT for high-risk R/R AML pts. Future clinical trials are warranted to explore additional modifications to this combination in order to optimize therapy for this group of high-risk and heavily treated R/R AML pts.
Flow cytometry minimal residual disease assessment in peripheral blood of adult acute lymphoblastic leukemia patients.
Authors: Minkovsky Alissa , Charest Karry , Schmidt Ryan , Briggs Debra , DeAngelo Daniel J. , Li Betty , Morgan Elizabeth , Pozdnyakova Olga 
Published: September 2018

e18517 Background: Multiparametric flow cytometry (FC) of bone marrow aspirate (BM) is a widely used method of minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL). In practice, ALL with hematogone-like phenotype and patients with recurrence of isolated extramedullary disease present challenges in accurate determination of MRD status. We hypothesized that addition of FC MRD of peripheral blood would aid in the interpretation of MRD status. Methods: 76 matched BM and PB specimens were analyzed independently for presence of ALL MRD by 6-color FC. Results: The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. PB MRD sensitivity and specificity relative to BM MRD was 13% [95% confident interval (CI) 2%-42%] and 98% [88-100%] for B-ALL samples (n = 65) and 67% [13%-98%] and 75% [36%-95%] for T-ALL samples (n = 11), respectively. We identified 2 cases with evidence of leukemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM. Conclusions: PB MRD demonstrates high specificity with relatively low sensitivity, especially in B-ALL when compared to T-ALL. The use of combined PB and BM samples in MRD assessment by current FC methods may have added clinical and diagnostic value in patients with high risk of extramedullary relapse, including PB MRD as a non-invasive method for monitoring of systemic relapse.
Comparison of myeloablative vs reduced intensity conditioning regimens in stem cell transplantations for acute myeloid leukemia.
Authors: Gurman Gunhan , Aydemir Guloksuz Gozde , Atilla Erden , Ataca Atilla Pinar , Civriz Bozdag Sinem , Kurt Yuksel Meltem , Toprak Selami Kocak , Topcuoglu Pervin , Ozcan Muhit , Arslan Onder , Demirer Taner , Akan Hamdi , Ilhan Osman , Beksac Meral 
Published: September 2018

e18518 Background: The development of reduced intensity conditioning (RIC) regimens enabled allogeneic hematopoietic stem cell transplantations (allo-HSCT) also for patients who had contraindications and comorbidities for myeloablative conditioning (MAC) regimens. The aim of this study is to evaluate the effects of conditioning regimens on outcomes of alllo-HSCT for patients with acute myeloid leukemia. Methods: We retrospectively analysed 362 acute myeloid leukemia patients who underwent allo-HSCT between November 1989 to November 2016. We compared the outcomes of MAC vs RIC by Fisher’s test and chi-square test. Results: Engraftment was achieved in 87% of RIC and 95% of MAC recipients (p = 0.03).Incidences of acute and chronic graft vs host disease were not statistically different in groups (41% vs 47%, p = 0.7; 32% vs 43%, p = 0.2).Relapse rate was higher in RIC group (45% vs 25%, p = 0.02).Both 1-year overall survival (OS) and 1-year relapse free survival (RFS) rate were lower in the patients treated with RIC (71% vs 35%; 55% vs 16%).The higher OS was related with patients who were transplanted in remission, received grafts from related donors as well as having acute and chronic graft vs host disease. Conclusions: In the treatment of young patients who do not have comorbidities for intense conditioning regimens, show good performance status and are high risk; the initial use of standard myeloablative conditioning regimens is feasible. However, the lower number of RIC transplants and the variations between groups in terms of patient and donor characteristics might effect the results of this study. [Table: see text]
A validated symptomatic BKV risk assessment score in patient post allogeneic stem cell transplant.
Authors: Abudayyeh Ala , Lin Heather Y. , Abdelrahim Maen , Rondon Gabriela , Andersson Borje , Martinez Charles , Tarrand Jeffery , Chemaly Roy , Kontoyiannis Dimitrios P , Marin David , Olson Amanda Leigh , Champlin Richard E. , Shpall Elizabeth J. , Rezvani Katayoun 
Published: September 2018

e18536 Background: BKV, Polyomavirus hominis 1, is a member of the family Polyomaviridae, is a non-enveloped virion; in the 1980s, it emerged as an important pathogen in SCT recipients. In the absence of sufficient T-cell immunity, BKV reactivation can progress, leading to prolonged hospital stays and increased mortality secondary to late hemorrhagic cystitis, ureteral stenosis, and nephropathy. In our recently completed retrospective study of 2477 SCT patients, 38.1% had developed renal impairment, and BKV viruria was present in 25%. In addition, BKV was found to be an independent predictor of chronic kidney disease and shorter survival. Using the large cohort (2477) patients studied earlier (2004-2012) we have derived a grading system to identify patients with risk of symptomatic BKV. We hypothesize that the current grading system will identify the patients at risk of symptomatic BKV at day 30 post allogeneic stem cell transplant. Methods: We performed a retrospective chart review of all patients who underwent allogeneic SCT from 2012-2016. The data was extracted from the secured database at MD Anderson cancer Center. Using the three variables that were significant predictor for symptomatic BKV derived from our initial study (conditioning regimen, HLA donor status, & underlying cancer diagnosis) we performed the analysis. Predicted cumulative incidence rate of BK infection at 30 days after transplant in 1308 patients were calculated in the presence of death as a competing risk using the “BASELINE” statement in PHREG procedure in SAS. Patients were classified into low, moderate and high risk according to the distribution of the predicted cumulative incidence of BK infection 30 days after transplant. Results: We have shown that the grading system derived from allogeneic SCT population predicted accurately the high, moderate & low risk population for developing symptomatic BKV. Conclusions: We have created and validated a grading system for symptomatic BKV in a large cohort of (1308 patients) to predict risk at day 30 post allogeneic SCT. Using this grading system we would hope to identify high risk patients for BKV and intervene early with novel therapies prior to complications associated.
Outcomes of blast phase chronic myeloid leukemia (BP-CML) in the tyrosine kinase inhibitor (TKI) era.
Authors: Talati Chetasi , Isenalumhe Leidy Lismeri , Shams Samantha Reiter , Kuykendall Andrew Tucker , Chavez Julio C. , Shah Bijal D. , Sweet Kendra Lynn , Pinilla-Ibarz Javier 
Published: September 2018

e18546 Background: Primary goal in management of chronic myeloid leukemia (CML) is to prevent progression to BP-CML. Even with the use of induction chemotherapy with a TKI, outcome remains dismal in BP-CML. We describe our experience with the management of BP-CML. Methods: Retrospective chart review was performed on CML patients treated between 2001 and 2016. Out of 585 CML cases, 58 (10%) had a diagnosis of BP-CML. Kaplan-Meier method with log-rank test was utilized for survival calculations. All p-values calculated were two sided. Results: The overall survival (OS) of BP-CML cohort was 31.9 months (mo) from diagnosis. In the patients diagnosed in chronic or accelerated phase, median time to progression to BP-CML was 19.1 mo. The median OS from the BP-CML diagnosis was not different when progressed from an earlier phase compared toBP-CML (10.8 vs 11.0, p 0.62). Trend toward worse OS was noted in myeloid BP-CML compared to lymphoid BP-CML (9.2 vs 17.5 mo, p 0.32). The median OS in the single agent TKI cohort (n=21) was 12.8 mo vs 10.9 mo (p 0.72) in the combination cohort (n = 36). Treatment with a single agent TKI vs combination therapy did not significantly impact OS in either myeloid (9.2 vs 9.1 mo, p 0.32) or lymphoid (14.5 vs 18.3 mo, p 0.24) BP-CML. Out of 26 patients (44.8%) who received allogeneic stem cell transplant, 26% (n=6) received a single agent TKI prior to transplant and 76.9% (n=20) received combination therapy. A trend toward improved OS was noted in the single agent TKI cohort (128.5 vs 24.0 mo, p 0.23). When stratified by the presence of standard Philadelphia chromosome or with additional cytogenetic aberrations, no difference in OS was noted (10.9 vs 12.1 mo, p 0.51). Monosomy 7 was present in greater frequency in lymphoid BP-CML than myeloid BP-CML (35.7% vs 6.3%, p 0.02). Conclusions: Our data suggest no survival difference when BP-CML is treated with a single agent TKI compared to a combination therapy, regardless of histology type. Therefore, single agent TKIs should be considered as an effective frontline therapy option for BP-CML, which may prevent the potential toxicity associated with chemotherapy. These findings need further validation in a larger prospective cohort.
Patients with myeloproliferative neoplasms (MPN) who later develop ph+ chronic myelogenous leukemia (CML): A case series.
Authors: Patel Shahina , Kim Seo-Hyun , Shammo Jamile M. , Radich Jerald P. , Terebelo Howard R. 
Published: September 2018

e18563 Background: Myeloproliferative Neoplasms are divided by the presence or absence of the Philadelphia Chromosome. Ph- MPN, typically possess driver mutations of JAK-2, MPL and CALR. CALR is involved with apoptosis and cell proliferation . MPL leads to TPO receptor stimulation and mutations are reported as a known cause of AA. JAK-2 mutations render hematopoietic stem cells more sensitive to growth. Though the true incidence is unknown, there are infrequent reports of pts with ET who later develop CML. CALR, MPL and JAK-2 mutations may have some further role in determining whether these are two separate events or clonally derived. We report three pts with MPN who later developed CML. Methods: Chart Review Results: Pt 1 had ET, diagnosed 21 yrs earlier treated with hydroxyurea. He then developed a rising WBC and platelets which necessitated a marrow which detected Ph+ CML. He was CALR positive. NGS was negative for nondriver mutations. Platelets initially declined from 3 million to 975K with TKI and he achieved a MMR. However, the inability to control his thrombocytosis required the addition of ruxolitinib. Pt 2 was diagnosed with ET and was treated with P32. Nine yrs later CML was diagnosed and TKI administration achieved a MMR. Subsequently, a profound anemia evaluation diagnosed PNH requiring eculizumab without benefit and repeat marrow with NGS revealed a MPLmutation and post-ET myelofibrosis. Pt 3 presented with a JAK-2 positive mutation and Polycythemia Vera. After four yrs of hydroxyurea extreme leukocytosis led to a marrow revealing a diagnosis of Ph+ CML. Dasatinib achieved a prompt MMR. NGS revealed KIT D618 V , coinciding with a diagnosis of systemic mastoytosis (SM). Conclusions: The rare observation of patients with both ET and CML have been reported by others with some recent implications of CALR as a common clone with double-mutant properties of CML. Our patients had a lead time of 21, 9, and 4 yrs, all having different mutations. Pts with MPN who develop unexplained leuko or thrombocytosis should be evaluated for CML.We plan to retrieve archival tissue to perform serial genetic analyses. Further work is required to determine whether these events are stochastic or represents clonal evolution.