bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment, healthcare resource utilization, and costs associated with non-metastatic and metastatic castration-resistant prostate cancer: A claims analysis.
Authors: Valderrama Adriana , Tangirala Krishna , Babajanyan Svetlana , Appukkuttan Sreevalsa , Wen Lonnie Kent , Malacan Jean , Shore Neal D. 
Published: September 2018

e18341 Background: Limited evidence exists about economic burden in non-metastatic castrate resistant prostate cancer (nmCRPC). The aim of this study was to describe the real-world treatments in this setting and to quantify both the costs and healthcare resource utilization (HCRU) during the year before and after metastasis for this patient population. Methods: A retrospective cohort of metastatic castrate resistant prostate cancer (mCRPC) patients was identified from Truven Health MarketScan database from January 2009 to March 2015 with metastasis diagnosis as index date. mCRPC algorithm was based on ICD-9 codes for both prostate cancer and secondary metastatic disease, and a subsequent claim for a FDA approved treatment for mCRPC. Patients were also required to have evidence of surgical or medical castration in the baseline period to define nmCRPC. Costs and HCRU were compared in the 1 year pre- and post-index time periods. Results: Among 341 mCRPC patients identified, mean age was 71.9 years (72.4% ≥65 years old), 72.7% were Medicare Advantage patients and 19.4% had Klabunde comorbidity > 1. Most common treatments in the pre index period were bicalutamide (90%), leuprolide (83.6%), docetaxel (27.6%), abiraterone (22.9%) and ketoconazole (21.4%). Mean per patient per year (PPPY) all cause HCRU and costs were significantly higher (all P < 0.05) in the mCRPC patients compared to nmCRPC patients (Table). Conclusions: Average yearly costs more than doubled following mCRPC diagnosis, which indicates the need for appropriate management strategies for nmCRPC patients in order to optimize the potential delay of disease progression. [Table: see text]
Real-world prescribing patterns in acute myeloid leukemia in the United States.
Authors: Medeiros Bruno C. , Pandya Bhavik J. , Hadfield Anna , Wilson Samuel , Mueller Cynthia , Bailey Tom , Flanders Scott , Horvath Laura E. , Rider Alex 
Published: September 2018

e18524 Background: The effective treatment of patients with acute myeloid leukemia (AML) remains a challenge in clinical practice. This analysis describes the patient characteristics and real-world use of AML treatments in the United States for patients on high- and low-intensity treatment. Methods: Data from the Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey conducted between February–May 2015, were analysed. A total of 61 hematologist/hem-oncologists, across academic, non-academic and office-based practice locations, provided data on 457 AML patients. Patient characteristics were derived from physician-completed patient record forms where each physician was asked to provide treatment details, including the treatment intensity, for each line of therapy. Results: A total of 91% (n = 415) of patients included in this analysis were previously untreated for AML. Patients had a mean age of 60 years and been diagnosed with AML for a median of 5.0 months. At first-line induction therapy, over half (53%; n = 241) of the patients were initiated on a high-intensity treatment, the most common regimen being cytarabine plus anthracycline (61%; n = 147). The remaining 47% (n = 216) of patients received a low-intensity induction therapy such as low dose cytarabine monotherapy (28%, n = 61), azacitidine monotherapy (25%, n = 54), or decitabine monotherapy (21%, n = 45). Over half (55%, n = 62) of patients suited to high intensity treatment went on to receive cytarabine monotherapy during the consolidation phase of their first-line treatment. Conclusions: According to treating physicians, the large majority of patients receive traditional, well-established therapies at first-line induction for AML. Whilst cytarabine combinations dominate the high-intensity treatment setting, the hypomethylating agents, azacitidine and decitabine, are frequently used for those more suited to low-intensity treatment.
Determinants of quality of life in patients with acute myeloid leukemia.
Authors: Buckley Sarah A. , Jimenez-Sahagun Diana , Othus Megan , Walter Roland B. , Lee Stephanie 
Published: September 2018

e18528 Background: There is growing interest in quantifying quality of life (QOL) effects of acute myeloid leukemia (AML) therapy. As there are no AML-specific QOL instruments available, we conducted a cross-sectional study to elicit concepts for the development of such an instrument, the AML-QOL. Methods: Adults with AML at various time points during the course of participated in an open-ended interview and completed the FACT-G, -LEU, -BMT and the PROMIS-29 questionnaires in order to elicit concepts impacting QOL. In addition, patients were asked to quantify the degree to which each impacted their QOL on a 3-point scale (little, some, large impact). Positive concepts (i.e., sources of support) were included in the AML-QOL based on prevalence; negative concepts were included based on both prevalence and the percent of cases in which the concept had high impact on QOL. Results: Among 82 patients, commonly described positive concepts were family support (85%), maintaining a positive attitude (63%), friends or community (52%), and trust in the medical team (52%). Negative concepts with the highest prevalence and impact product are shown in the Table. After completing FACT and PROMIS, 22% of patients reported confusion with items querying functional status because of ambiguity between temporary functional restrictions (e.g., inability because of an inpatient stay) and functional limitations (e.g., inability due to weakness). Conclusions: Our interviews identified concepts most important to patients during AML therapy and allowed development of a 40-item survey that is now undergoing validation. [Table: see text]
Neutropenic fever prophylaxis during induction therapy for acute myeloid leukemia.
Authors: Nabbout Nassim H. 
Published: September 2018

e18531 Neutropenic Fever Prophylaxis During Induction Therapy for Acute Myeloid Leukemia Nassim Nabbout, MD, Salam Kadhem, MD, Rawaa Ebrahem, MD, Rossa Khalaf, MD, Baharat Malhotra, MD, K. James Kallail, PhD Background: Neutropenic fever is an oncological emergency [1] that occurs at a high rate in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. Oral antibiotics have been considered standard of care for prophylaxis for these patients once they develop neutropenia [2]. To determine the efficacy of this approach, we conducted a retrospective review of newly diagnosed AML patients. Methods: All adult patients who underwent induction treatment for newly diagnosed AML at one Wichita, Kansas medical center between January 1, 2011 and December 31, 2013 were identified. The medical records were reviewed and pre-specified variables were collected. Results: Thirty-eight patients were included and their charts were reviewed. Nineteen (50%) were males. Thirty-six patients (95%) were white. The average white blood count on day 1 of treatment was 34000 cell/mm3 and the range was 1300 - 305,000 cell/mm3. The average ANC was 3700 cell/mm3 with the range of 10 - 28288 cell/mm3. All patients received prophylactic oral antibiotics once they became neutropenic. In all, but one patient, this regimen consisted of combination of levofloxacin, acyclovir, and fluconazole. Thirty-four patients (89%) developed neutropenic fever while they were on oral prophylactic antibiotics. Two patients (5%) developed septic shock. Four patients (11%) died during the first 21 days of induction, all due to infections, and three (8%) went to hospice. Causative organisms were identified in 11 patients (29%). All patients were switched to intravenous vancomycin and cefepime once they became febrile. Conclusions: Eighty-nine percent of patients developed neutropenic fever despite prophylaxis with oral antibiotics. These dismal results suggest that the current standard of care for neutropenic fever prophylaxis is ineffective and highlight the need for a different approach. Future studies should consider changing the regimens of antibiotics and/or the route of administration toward more aggressive prophylactic strategies.
Intensive sequential chemoterapy with etoposide, mitoxantrone and cytarabine (EMA) as salvage in patients with AML relapsing after hematopoietic stem cell transplantation.
Authors: Gokmen Ayla , Soydan Ender , Gokgoz Zafer , Ozkumur Kerem ozan , Arslan Onder , Ilhan Osman , Ozcan Muhit 
Published: September 2018

e18537 Background: Relapse after allogeneic hematopoietic stem cell transplantation ( HSCT) for AML is the main cause of treatment failure.The optimal treatment strategy for patients with AML relapsing after HSCT remains controversial. We evaluated the efficacy of intensive sequential chemotherapy with etoposide,mitoxantrone and cytarabine as salvage therapy in patients with AML relapsing after alloHSCT. Methods: Fifteen AML patients relapsing after HSCT who were treated with EMA regimen between January 2015 and December 2016 were analysed retrospectively. EMA regimen consisted of mitoxantrone 12 mg/m² on days 1-3, etoposide 200 mg/m² on days 8-10 and cytarabine 500 mg/m² on days 1-3 and 8-10. Results: Median age was 49 ( range 22-64) years. At transplantation , 12 patients were in CR ( 10 CR1 and 2 CR2) , 3 patients had active disease. 9 donors were matched related, 3 were matched unrelated and 3 were haploidentical. Median time from transplantation to relapse was 163 ( 62-576) days. Complete response ( CR) was achieved in 7 of 15 patients ( 46.6 %). Five patients died during treatment before assessment of response to treatment with a median day of 32 due to infection. Three patients did not respond to treatment. All patients suffered grade 4 neutropenia and thrombocytopenia. Neutropenic fever was obseved in all patients. Grade 2-3 a GVHD was observed in 10 patients (66%) during EMA chemotherapy at a median day of 15. Further treatment was given in 6 patients who achieved CR with EMA : 2 patients underwent second allogeneic HSCT, 1 patient underwent second haploidentical HSCT, 2 patients were treated with DLI, 1 patient was treated with azacytidine-DLI combination. Median OS was 100 d ( range 24-402). Median duration of OS in responding patients were 248 d ( 67-402). At last folllow-up 3 patients are still alive and disease free. Conclusions: Intensive sequential chemotherapy with EMA is an efficacious option as salvage therapy in patients with AML relapsing after HSCT. However further treatment strategies such as second transplantation, DLI after chemoterapy or maintanence with targeted drugs are required to obtain long term remission.
Magnesium alterations of graft immune cells (MAGIC).
Authors: Sedhom Ramy , Zloza Andrew , Kohlhapp Frederick Joseph , Medina Daniel , Strair Roger 
Published: September 2018

e18541 Background: Magnesium plays important roles in cellular processes. Allogeneic hematopoietic stem cell transplantation provides potentially curative therapy to patients with a variety of hematologic malignancies. A common abnormality post transplant is hypomagnesaemia. Recent studies identified magnesium transporter 1 deficiency in association with XMEN syndrome. These patients exhibit low intracellular [Mg++] and low T cell and NK cell NKG2D expression. Therefore, we investigated this potential functional link between magnesium deficiency and immune function in patients post transplant. Methods: A pilot study investigated whether detectable changes in T and NK cells were associated with IV magnesium repletion post hematopoietic transplant. Blood was obtained before and after magnesium transfusions. Immunophenotypic analysis of T and NK cell NKG2D levels using commercially available monoclonal antibodies (CD3, CD16, CD56, CD4, CD8, CD314 [NKG2D]) was performed. Samples from patients demonstrating an increase in NKG2D expression were subsequently analyzed for ex vivo NK activity. Here, NK activity and cytotoxicity of Jurkat cells were assayed using standard laboratory techniques and changes > 2 fold were considered significant. A total of 7 patients were enrolled. Results: NKG2D expression on T and NK cell subsets were determined by flow cytometry using commercially available monoclonal antibodies. NK reactivity and killing of K562 were undertaken using standard cytotoxicity assays. Our findings indicate a significant response in five of the seven enrolled patients. NKG2D expression on CD8+ T cells increased by up to 31%. Conclusions: Our results suggest that magnesium infusions post allogeneic transplant are associated with augmented NKG2D expression on immune cells. Additional studies are needed to clarify the mechanisms by which therapeutic magnesium repletion restores the cytotoxicity of NK cells and T lymphocytes. Although the clinical utility of magnesium supplementation remains to be validated, our data indicate that NKG2D is regulated by magnesium post transplant and magnesium may play a key role in immune regulation.
Bortezomib, rituximab, and risk of graft-versus-host disease (GVHD) after BEAM conditioning for allogeneic stem cell transplantation (alloSCT).
Authors: Chamoun Kamal , Gulbis Alison M , Milton Denai , Jabbour Elias , Turturro Francesco , Khouri Issa F. 
Published: September 2018

e18543 Background: GVHD remains the main limitation of alloSCT and is exacerbated by the intensity of the conditioning regimen. In a recent study, the risk of acute grade II-IV GVHD and extensive chronic GVHD (cGVHD) after a nonmyelobaltive (NMA) regimen was 11%, and 26%, respectively (Khouri I. Blood 2014 124:2306). Higher rates were previously observed (32% and 54%, respectively) with the BEAM regimen. Based on clinical data showing a reduction in GVHD with the use of rituximab or bortezomib, we conducted a phase I/II study evaluating the addition of bortezomib to rituximab+BEAM in patients (pts.) who were not eligible for NMA alloSCT. Methods: Bortezomib was administered at 1.3 mg/m2 IV on days -13, -6, -1 and +2. The dose was later reduced to 1 mg/m2 after the occurrence of C. Difficile colitis in the first 3 pts. leading to 2 deaths. Rituximab was given on day -13 at a dose of 375 mg/m2, then at 1000 mg/m2 on days -6, +1, and +8 of alloSCT. BEAM was administered between days -6 and -1. All pts. received our standard GVHD prophylaxis with tacrolimus and methotrexate. In addition, thymoglobulin 1 mg/kg IV was given on days -2, and -1 in patients receiving matched unrelated donor (MUD) or mismatched (MM) transplants. Results: Thirty-nine pts. were studied. Median age was 54 yrs. Thirteen (33%) and 26 (67%) pts. had indolent or aggressive lymphoma histologies, respectively. Sixteen (41%) pts. were refractory. Twenty-two (56%) received alloSCT from HLA-compatible siblings, 16 (41%) from MUDs and 1 (3%) from mm donors. Peripheral blood was the source of stem cells in 97% of pts. ABO and CMV-mismatch rates were 56% had 50%, respectively. Median follow up surviving patients was 65 mos. Five-year OS and PFS rates were 35% and 28%, respectively. The CI of acute grade II-IV, III-IV, and cGVHD were 55%, 34%, and 41%, respectively. No predictor for acute GVHD was identified. Instead, we found that sex-mismatched transplants were predictive of a higher risk of cGVHD ( P= 0.01). Conclusions: The current trial is the first one evaluating the safety and efficacy of bortezomib plus rituximab as a part of the BEAM regimen for alloSCT. A better prophylaxis regimen is needed to lessen the risk of GVHD in this setting. Clinical trial information: NCT00439556.
Musculoskeletal symptoms in chronic myeloid leukemia patients after stopping tyrosine kinase inhibitors.
Authors: Diab Maria , Jeyakumar Ghayathri , Schiffer Charles Alan 
Published: September 2018

e18547 Background: TKIs have revolutionized outcomes for CML patients (pts) but are not without cost or side effects. For pts with a prolonged response to treatment, discontinuing (d/c) treatment is appealing and has been investigated in a number of trials. In pts in whom treatment was stopped, musculoskeletal (MSK) symptoms were reported that were shown in some cases to resolve with resuming TKIs. Methods: Records of pts with chronic phase CML who stopped TKIs were reviewed. Results: We report 8 pts with chronic phase CML whose TKI was stopped following a prolonged molecular remission. 5 pts were receiving imatinib and 3 dasatinib. 5 pts were experiencing intolerable side effects of TKIs and agreed to a trial of d/c; 2 pts requested d/c; a third pt was planning for pregnancy. The median duration of therapy with TKI before d/c was 10 years. 6/8 pts developed MSK complaints with arthralgias and joint stiffness after cessation. Involved joints included the cervical spine, shoulders, elbows, small joints of the hand, hips and knees. Arthralgia was Grade 1 in 3 pts, and Grades 2 and 3 in 1 and 2 pts, respectively. Joints were not swollen, erythematous or tender to touch. The median time from cessation of TKIs to the onset of symptoms was 2.25 mos (range: < 1-6 months). 3 pts with symptoms underwent rheumatologic work up that was nonrevealing. 5/8 pts remain in molecular remission. Of the 3 with molecular relapse, 2 had arthralgias that improved with resuming TKIs; the third remained asymptomatic. Of those who did not relapse, 1 remains symptom-free and 2 had resolution of their MSK symptoms. 1 had little benefit with corticosteroid therapy and imatinib was resumed. However, this retreatment was d/c due to side effects and she continues to experience mild arthralgias. 1 pt did not benefit from resuming TKIs, which was therefore d/c. Conclusions: The etiology of the so-called TKI “withdrawal syndrome” remains unclear. The incidence of this syndrome has not been fully elucidated, and it seems to be underappreciated and perhaps under-reported by patients. Although most symptoms are relatively mild and self-limited, this should be discussed with patients considering stopping TKIs.
Generic imatinib therapy among Jordanians: An observational assessment of safety and efficacy in routine clinical practice.
Authors: Awidi Abdallah , Abbasi Salah Y. , Al-Rabi Kamal Hosni , Kheirallah Khalid 
Published: September 2018

e18548 Background: Generic imatinib therapy is being globally considered due to cost considerations. Evidence about its efficacy and safety in developing country settings, however, is scarce. Methods: The efficacy and safety of generic imatinib among Jordanian patients diagnosed with chronic myeloid leukemia (CML) was assessed utilizing an observational, multicenter, prospective study design. All patients (N = 91) were adults with CML treated with generic imatinib, mainly 400 mg/day, who either received generic imatinib (n = 33) as first-line therapy “first-line patients “or switched from patented imatinib to generic imatinib “switched patients” (n = 58). The primary objective was to measure proportions (95% Confidence Interval (CI)) of optimal response for first-line and switched patients at 12 months of treatment with generic imatinib, as defined in the 2009 ELN guidelines (CCyR [no Ph+ metaphases], or MMR [a ratio of BCR-ABL1 to ABL1 ≤0.1% on the International Scale]) and assessed by complete blood counts, fluorescence in situ hybridization and real-time quantitative PCR. Results: A total of 84.8% (n = 28/33) of the first-line patients achieved complete hematologic response (CHR) within 3 months of starting generic imatinib therapy (100% after 6 months). Out of the 23 evaluable first-line patients, [(87%, 95% CI = 73% - 100%), (n = 20)] in the per-protocol population (60.6 %, 95% CI = 51% - 86%) of the 33 patients in the intention-to-treat (ITT) population) achieved an optimal response at 12 months. All 58 switched patients had CHR at enrollment. Out of the 55 evaluable switched patients, [(96.4%, 95% CI = 91%-100%), (n = 53)] in the PP population (91.4%, 95% CI = 83%-98%) of the 58 patients in the ITT population) gained or maintained an optimal response at 12 months after switching to generic imatinib therapy. Most (84.7%, n = 144 out of 170) adverse events (AEs) were mild. Frequencies of drug-related AEs were similar to patented imatinib. Conclusions: Efficacy and safety of generic imatinib among middle eastern population in routine clinical practice is comparable to that of patented imatinib, and to that of the global population. Clinical trial information: NCT02977312.
Correlation of patient prognosis with PU.1 and JDP2 to provide potential novel prognostic/diagnostic markers in MDS.
Authors: Simpson Rachael , Goddard Alan , Lally James , Simmonds Matthew , Rinaldi Ciro Roberto 
Published: September 2018

e18558 Background: PU.1 is a key transcription factor in haematopoiesis that plays important roles in various haematological malignancies. Previously, significant down-regulation of PU.1 has been reported in high risk myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) patients. Methods: To clarify PU.1 molecular function we investigated the gene expression of PU.1 and JDP2 (c-Jun dimerization protein-2), a member of the activating protein-1 family located downstream of PU.1, in bone marrow from 12 MDS patients stratified according to IPSS-R score (6-low, 3-intermediate, 3-high risk), 1 AML patient and 10 normal controls. Samples were enriched for the mononuclear fraction by Ficoll separation. Total RNA was extracted and analysed by Real Time PCR for PU.1 and JDP2 expression relative to the housekeeping gene GAPDHusing the 2-ΔΔCT method. Results: We revealed both PU.1 and JDP2 are down regulated in MDS. In addition, our data suggests that PU.1 and JDP2 expression inversely correlates with disease, with expression of these genes consistently reducing according to IPSS-R groups. Furthermore, a positive correlation of PU.1 and JDP2expression < R = O.9333, s = 0.0004 > , provides additional evidence that suppression of JDP2 by PU.1 could contribute to the pathogenesis of AML. Notably, PU.1 and JDP2 do not correlate to the same extent in normal HSCs, indicating that cofactors are required for PU.1 to exert its JDP2-regulating function and that such cofactors are not present under normal conditions. To confirm that JDP2 suppression is a direct result of reduced PU.1 we performed PU.1-knockdown in K562 cells stably expressing PU.1 short interfering RNAs versus control cells. These analyses reveal only a partial reduction in JDP2 expression when analysed by RT-PCR and Western blot, suggesting a more complex regulatory mechanism. Additionally, both PU.1 and JDP2 expression was recovered by treatment with azacitidine, which is routinely used to treat MDS, suggesting an involvement in treatment response. Conclusions: PU.1 and JDP2 expression correlates with patients prognosis highlighting a potential role as new diagnostic and prognostic markers in MDS.