bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Results of a Clinical Trial Using Targeted Oncolytic Virotherapy in Kaposi Sarcoma Herpes Virus (KSHV) Associated Multicentric Castleman’s Disease (MCD).
Authors: O’Mahony Deirdre , Bernstein Wendy , Wyvill Kathy , Aleman Karen , Whitby Denise , Steinberg Seth , Tosato Giovanna , Pittaluga Stefania , Jaffe Elaine S. , Yarchoan Robert , Little Richard F. 
Published: October 2019

Abstract
Human herpes virus 8, also termed KSHV, is an oncogenic gamma herpesvirus associated with Kaposi’s sarcoma (KS), primary effusion lymphoma and MCD. KSHV-associated MCD (KSHV-MCD), a rare B-cell lymphoproliferative disease almost universally found in association with HIV infection, is characterized by recurrent flares of a systemic syndrome of fatigue, fevers, cytopenias, elevated serum C-reactive protein (CRP), and lytic KSHV replication. Prognosis is poor (median survival 14 months). KSHV open reading frames (ORF) 21 and 36 respectively have the ability to phosphorylate zidovudine and ganciclovir, leading to cell death (Cancer Res2007;67(14):7003–10), and this may be exploitable for oncolytic virotherapy. Ten patients (pts) with symptomatic and biopsy confirmed KSHV-associated MCD have been treated with high dose oral zidovudine (HDAZT) 600mg every 6 hours and valganciclovir (VGCV) 900mg every 12 hours. Treatment length of first cycle is dependent on response, and ranges from 7–21 days. Subsequent cycle length is 21 days with 7 treatment days. Pt characteristics: median age 40 (range 33–56); ECOG PS 2 (1–3); median enrollment CD4 count 189 (range 19–1319 UL); median HIV viral load <50 copies/ml3 plasma (range <50 to 27,500). All pts were on highly active antiretroviral therapy; this was adjusted during time pts were on AZT. 8 pts had a history of KS. Median duration of MCD 3.5 months (range 0.5–45 months); seven pts had received at least one prior therapy for MCD (range 1–6). All had MCD-related constitutional symptoms and CRP above 0.8mg/dl (median 13.1, range 1.06–38.7 mg/dl) at treatment initiation. A total of 83 cycles have been administered to date, with a median of 6 (range 4–23) cycles per pt. 9/10 had documented improvement in constitutional symptoms, C-reactive protein levels or cytopenias. Therapy continues in 5 patients who have had sustained responses (median duration on therapy 7 months, range 3–18). Response was only short-lived in 4 (median duration on therapy 4.5 months, range 3.5–6.5) who then received alternative treatments. Grade (gr) 3 or 4 hematologic toxicity not attributable to disease was seen in only 2 patients. Two infectious events occurred, a staphylococcal skin abscess and streptococcal meningitis. There were no neutropenia associated infections. Treatment toxicity included two patients with fatigue (gr3), 1 with nausea (gr3), 1 with transaminitis (gr3) and one with insomnia (gr3). In summary, this preliminary data suggests that HDAZT and VGCV has activity useful in the management of KSHV-associated MCD. Accrual continues.
Medical Visit Patterns in Cancer Chemotherapy Patients Receiving Erythropoiesis-Stimulating Agents in a Managed Care Setting.
Authors: McKenzie Scott R. , Lefebvre Patrick , Bookhart Brahim K. , Laliberté François , Duh Mei S. 
Published: October 2019

Abstract
Background: Avoiding unnecessary medical visits related to erythropoiesis-stimulating agent (ESA) treatment represents an important consideration for managed-care organizations. Observational data have reported varying visit patterns for cancer chemotherapy patients receiving epoetin alfa (EPO) and darbepoetin alfa (DARB). Few studies have characterized visit patterns in this population during ESA treatment.
Objective and Purpose: The objective of this analysis was to describe visit patterns and identify the proportion of medical visits made exclusively for ESA treatment in cancer chemotherapy patients.
Methods: Analysis of medical claims between 1/2004–12/2005 using the Integrated Health Care Information Systems national database, representing >35 health plans, was conducted. Patients were ≥18 years old, had a cancer diagnosis, received >1 ESA administration, and concurrent chemotherapy (during or within 14 days of ESA initiation). Medical visits during the ESA treatment duration (time from first to last ESA administration) were categorized into mutually exclusive groups based on procedure codes recorded on the visit day: ESA administration, chemotherapy/radiotherapy administration, physician visit, blood count, WBC growth factor administration and other (hydration, antiemetics/antibiotics, etc).
Results: 3,462 EPO and 2,839 DARB patients were identified representing 107,149 unique visits (EPO 62,785, DARB 44,364). Mean ESA treatment duration was similar between groups (Days: EPO 59.3; DARB 57.6, p=0.212). The proportion of visits were categorized into mutually exclusive service groups, presented below.
Conclusion: Cancer chemotherapy patients receiving ESAs incurred visits for many reasons, but primarily for receiving chemotherapy. Less than 5% of all visits were solely related to ESA administration, regardless of ESA received.
Table Service Group EPO DARB Chemotherapy 10.3% 12.2% Chemotherapy + ESA 24.9% 27.3% Physician visit 11.9% 12.5% Physician visit + ESA 13.0% 9.9% Blood count 1.1% 2.1% Blood count + ESA 10.1% 8.4% WBC growth factor 0.3% 0.5% WBC growth factor + ESA 5.9% 6.8% Other 15.9% 14.8% Other and ESA 2.6% 2.6% ESA only 4.1% 2.9% Total 100% 100%
Multimethod Clinical Assessment of Patterns and Prevalence of Nonadherence (NA) to Imatinib Treatment (IMRx) in Patients (Pts) with Chronic Myeloid Leukemia (CML): Results from the ADAGIO Study.
Authors: van Lierde Marie-Anne , Serra Filipo , De Rop Larissa , Strobbe Eric , MacDonald Karen , Vancayzeele Stefaan , De Geest Sabina , Letvak Laurie , Albrecht Tara , Abraham Ivo 
Published: October 2019

Abstract
BACKGROUND. ImRx for CML is a long-term treatment. Patterns and prevalence of NA to ImRx remain largely unknown. Short-term NA trends may be indicative of long-term NA. Methods for clinical NA assessment vary in reliability. A multimethod approach is indicated.
OBJECTIVE. Multimethod estimation of patterns and prevalence of ImRx NA in CML pts at baseline (BL) and follow-up (FU) at 90 days (90d), incl. BL to 90d changes.
DESIGN AND PATIENTS. Data subset from prospective, 90d observational, open-label, multicenter study. 169 evaluable pts on ImRx for minimum 30d at enrollment [1].
METHODS OF NA ASSESSMENT. At BL (NA with prior ImRx) and 90d (NA during study): visual analog scale (VAS) for physicians (phs; mVAS), pts (pVAS), cos (cVAS); Basel Assessment of Adherence Scale for pts (pBAAS; structured interview re NA in past 4 weeks [4wks]); pts reported persistence (pPST); % clinic appointments (%CAPPTS) kept (if any scheduled). At 90d also: % of ImRx taken per pill count (%pts@ImRx).
RESULTS. See Table 1.
CONCLUSIONS. Intuitive adherence ratings (VAS) by phs, pts, and cos are very high and differ from those from structured interview, where about one-third of patients exhibited NA behavior in 4wks prior to BL and FU - despite high persistence. Pill count suggests patterns of under- and overtaking, with only 1 out 7 patients being perfectly adherent. Rate of clinic appointments may be affected by physician scheduling practices and collateral input is a function of availability of collateral person. Consenting to participate in the ADAGIO study did not reduce NA. Though patient self-reports in structured interview (pBAAS) and pill counts have inherent biases, both indices suggest that NA with ImRx may be similar to NA rates in other disease categories. Especially pBAAS and pill count may be useful rapid clinical assessment tools, with pBAAS having the benefit of validated categorical assessment (vs. continuous in other methods). Determinants of NA and the impact of NA on treatment outcomes must be examined.
Table 1 - Multimethod Assessment of Non-Adherence with Imatinib Method BL 90d n M±SD/Min-Max M±SD/Min-Max P mVAS 164 95.0±7.6/60–100 94.9±9.9/0–100 ns pVAS 169 95.3±8.5/25–100 95.7±6.1/75–100 ns cVAS 56 97.1±5.1/80–100 97.4±5.1/75–100 ns %pts@ImRx 162 - 91.0±21.1/29.5–2002.2 71.0% @ < 100% ImRx 14.2% @ 100% ImRx n % NA % NA P pBAAS 163 36.2% 32.5% ns %CAPPTS 51 94.1% 88.2% 0.001 pPST 163 98.8% 100.0% ns
Assesment of the Prevalence and Impact of Anemia on Women Hospitalized for Gynecologic Conditions Associated with Heavy Uterine Bleeding.
Authors: Morrison John , Patel Snehal , Dinh Quinn 
Published: October 2019

Abstract
Objective: Women with heavy uterine bleeding often are untreated or inadequately treated for anemia. This study was conducted to estimate the prevalence and impact of anemia in women hospitalized for gynecologic conditions associated with heavy uterine bleeding.
Study Design: The largest all-payer inpatient care database, the Healthcare Cost and Utilization Project’s 2003 Nationwide Inpatient Sample, was queried using ICD-9-CM codes to identify and group cases with gynecologic diagnoses associated with heavy uterine bleeding into two categories: with or without anemia. Groups were evaluated for demographic characteristics, medical resource utilization, and hospitalization costs using descriptive statistics.
Results: More than 25 percent of the estimated 300,589 women in the study had a diagnosis of anemia. Compared to patients without an anemia diagnosis, those with an anemia diagnosis were more likely to have a blood transfusion (24% versus 0.7%, p<0.0001); an emergency department admission (26.8% versus 3.2%, p<0.0001); and higher hospitalization costs ($5,631 versus $5,101, p<0.0001).
Conclusions: Anemia and blood transfusions are common in women hospitalized for gynecologic conditions associated with heavy uterine bleeding. Greater patient and provider awareness of the prevalence and burden associated with anemia may increase opportunities to reduce blood transfusions and improve general health status and quality of life in this patient population.
A Selective and Potent Oral Inhibitor of the JAK2 Tyrosine Kinase Reverses Polycythemia and Leukocytosis Induced by JAK2 V617F in a Mouse Model.
Authors: Zaleskas Virginia M. , Chan Wayne W. , Evangelista Peter , Lazarides Katherine , Chopra Rajesh , Zinda Michael , Huszar Dennis , Van Etten Richard A. 
Published: October 2019

Abstract
A somatic mutation (V617F) in the pseudokinase domain of the non-receptor tyrosine kinase JAK2 is found in virtually all patients with the myeloproliferative disease (MPD) polycythemia vera (PV), and about half of those with essential thrombocythemia and chronic idiopathic myelofibrosis. When expressed in mice by retroviral bone marrow transduction and transplantation, JAK2 V617F but not JAK2 wild-type induces leukocytosis with neutrophilia and recapitulates the entire erythroid phenotype of PV, with polycythemia, reticulocytosis, low plasma Epo, and endogenous erythroid colonies (Zaleskas et al., PLoS ONE2006;1:e18; Wernig et al., Blood2006;107:4274; Lacout et al., Blood2006;108:1652). By analogy to BCR-ABL in chronic myeloid leukemia, JAK2 V617F is therefore a rational target for therapy in PV and other JAK2 V617F+ MPDs. Previous studies with a nonselective and parenteral tyrphostin JAK2 inhibitor suggested that short-term inhibition of JAK2 could decrease reticulocytosis in recipients of JAK2 V617F-transduced marrow (Zaleskas et al., op cit.). Here, we studied one of a novel series of inhibitors of JAK2, AZ-01, which potently inhibited JAK2 kinase activity (IC50 < 1nM) and suppressed proliferation of cell lines carrying the JAK2 V617F mutation. We treated cohorts of Balb/c mice with JAK2 V617F-induced polycythemia and leukocytosis with AZ-01 at 10 mg/kg by oral gavage twice daily, or with vehicle alone. After 28 days of treatment, AZ-01-treated mice had significant reductions in hematocrit, hemoglobin, reticulocytes, and splenomegaly, as well as normalization of peripheral blood leukocyte counts (Figure 1). These results demonstrate that oral administration of a potent and selective JAK2 inhibitor can reverse the hematopoietic abnormalities of JAK2 V617F-induced MPD in mice, and validate JAK2 as a target for therapy of human JAK2 V617F+ MPD.
Figure Figure
An orally available JAK2 inhibitor decreases the leukocyte count, hematocrit, and reticulocyte count in mice with JAK2 V617F-induced MPD. Leukocyte count (left), hematocrit (center) and reticulocyte counts (right) of cohorts of mice with JAK2 V617F-induced MPD treated with vehicle or drug at 10 mg/kg BID. Blood counts were assessed at 15 and 28 days of treatment. Decreases in d28 hematocrit and retic count in the drug-treated cohorts were significant (p=0.008 and p<0.0001, respectively, t-tests).
Distinct Expression Patterns of microRNAs in Activated B Cell (ABC) and Germinal Center B (GC) Subtypes of Diffuse Large B Cell Lymphoma (DLBLC).
Authors: Bastie Jean-Noel , Jais Jean-Philippe , Molina Thierry , Come Emmanuelle , Coiffier Bertrand , Gisselbrecht Christian , Rickman David , de Reynies Aurelien , Briere Josette , Gaulard Philippe , Feugier Pierre , Tilly Herve , Salles Gilles , Haioun Corinne , Leroy Karen 
Published: October 2019

Abstract
The Micro RNAs (miRNAs) are small non-coding, single-stranded RNAs that regulate the expression of genes by hybridizing the mRNA target with complementary sequences that are followed by translational repression, mRNa cleavage or destabilization. There is evidence that miRNA play an important role in carcinogenesis. Aberrant miRNA expression has been found in a variety of human malignancies including B-cell leukemias and lymphomas. The purpose of this study is to determine the miRNA expression patterns in DLBCL and their relationship with clinical characteristics and outcome. We used high throughput quantitative RT-PCR technology (Taqman Low density Arrays) to analyze the expression profile of 365 different mature miRNA in 12 Diffuse Large B-Cell Lymphoma (DLBCL) samples which had been previously characterized at the transcriptional level with Affymetrix HU133A micro-arrays. MiR-155 expression was significantly lower in the 6 samples with a Germinal Center (GC) mRNA profile than in the 6 samples with an Activated B-Cell (ABC) profile. Expression of miR-155 and of different miRNA involved in lymphoid differentiation (miR-181a, miR127) or tumour pathogenesis (cluster miR 17–92) were further evaluated in a series of 64 patients with DLBCL treated with Rituximab associated with chemotherapy (R-CHOP). 28 patients had been enrolled in the LNH98.5 GELA trial between February 1998 and February 2000 and 36 were treated with R-CHOP in GELA centers after the closure of the LNH98-5 trial, between November 2000 and June 2004. The median follow up of these patients is 69 months. Patients median age at diagnosis was 69 years (range 59–82) and 28 patients presented with an International Prognostic Index (IPI) score of more than 3. Mature miRNA expression was determined by quantitative RT-PCR with Applied Biosystems specific miRNA primer and probe sets and normalized to U6 small nuclear RNA expression. MiR-155 expression was significantly higher in patients with a lymphoma of the ABC subtype, defined on the basis of the transcriptional profile (mean delta Ct = − 3.9 in the 41 ABC samples, mean delta Ct = − 1.67 in the 23 GC samples, p<0.00001) and significantly higher in patients with a high (4 or 5) IPI score (p=0.02). A high miR-155 expression was associated with a trend towards a poorer overall survival. The expression of miR-127, miR-181a and the cluster 17–92 were not correlated with clinical outcome. These analyses are currently being extended to a larger series of patients in order to determine whether other miRNA can be used to classify DLBCL samples into ABC and GC subtypes and whether some miRNA have prognostic significance in the era of treatments combining Rituximab and chemotherapy.
A Prospective Randomized Study of Rituximab and Dexamethasone vs Dexamethasone Alone in ITP.
Authors: Zaja Francesco , Mazza Patrizio , Vianelli Nicola , De Fina Marzia , Liso Vincenzo , Bonferroni Margherita , Usala Emilio , Cantoni Silvia , Ferrara Felicetto , Mirto Salvo , Visani Giuseppe , Fioritoni Giuseppe , Zaccaria Alfonso , Gugliotta Luigi , Mazzucconi Maria G. , Campagna Selenia , De Stefano Valerio , Veneri Dino , Carbone Cecilia , Semenzato Gianpietro , Soldano Franca , Gamba Enrica , Battista Marta , Baccarani Michele , Fanin Renato 
Published: October 2019

Abstract
Previous uncontrolled studies have highlighted the potential activity of Rituximab in patients with idiopathic thrombocytopenic purpura (ITP) relapsed or refractory to standard treatments. To better address this effect, a prospective randomized, multicenter, phase III study comparing treatment with Dexamethasone alone (arm A) vs Dexamethasone plus Rituximab (arm B) was started in July 2005 for adult patients with ITP according to the ASH guidelines. Main inclusion criteria were: age ≥ 18 years, untreated ITP, platelet (PLT) count ≤ 20 x109/L, HIV- HCV-HbsAg negativity, informed consent. Patients randomized to arm A received a single course of Dexamethasone 40 mg po on days +1, +2, +3, +4, while patients randomized to arm B received Dexamethasone (as in arm A) in association with Rituximab 375 mg/m2 iv on days +7, +14, +21, +28. Patients in arm A who failed to achieve a sustained response (SR) could be rescued with arm B treatment. The primary objective of the study was to compare SR, i.e. PLT ≥ 50 x 109/L at month + 6 of treatment. The secondary objectives were: the initial overall (OR= PLT ≥ 50 x109/L) and complete response (CR= PLT ≥ 100 x 109/L) by day 30 after starting treatment, respectively; the toxic profile. The statistical plan considered three interim analyses, after the first 50, 100 and 150 enrolled patients, with an estimated sample size of 198 patients (99 per arm). Table 1 summarizes the main demographic data and the results of efficacy and toxicity according to an intention to treat analysis of the first interim analysis. The toxic profile was characterized by only grade 3 adverse events (AE); no patient died during the study period. 16 patients of arm A were rescued with arm B. For this group SR was 81% and no patient experienced SAE or ≥ grade 3 AE. In accordance with the initial statistical plan of the study, which stated that patients’ recruitment would ceased if a ≥ 50% difference in sustained response was demonstrated, enrolment has been stopped in June 2007 with a total number of 103 randomized patients. This preliminary report indicates a significantly higher SR for arm B of treatment with no difference in toxicity profile. A final report will be prepared when the results on the entire study group will be available.
Table 1 Therapy Arm A Arm B Statistics Patients 24 26 Male/female 11/13 10/16 p = NS Age (median ± SD) 54.54 ± 18.78 48.65 ± 15.10 p = NS Initial OR 15 (62.5%) 18 (69%) p = NS Initial CR 10 (42%) 16 (61%) p = NS SR 7 (29%) 21 (81%) p = 0.0001 SAE or grade 3 AE 3 (12.5%) 2 (8%) p = NS
Circulating Angiopoietin-2 Predicts Time to Relapse after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.
Authors: Koenecke Christian , Kümpers Philipp , Lukasz Alexander , Hecker Hartmut , Dammann Elke , Verhagen Willem , David Sascha , Göhring Gudrun , Buchholz Stefanie , Weissinger Eva , Krauter Jürgen , Eder Matthias , Haller Hermann , Ganser Arnold 
Published: October 2019

Abstract
CK and PK contributed equally to this work. Angiopoietin-2 (Ang-2), a member of the Angiopoietin/Tie ligand-receptor system, represents one of the specific inducers required for angiogenesis. Recent data indicate that bone marrow neoangiogenesis plays an important pathogenic and prognostic role in malignancies of the hematopoietic system. We have recently shown that circulating Ang-2 is a predictor for relapse in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) in a cohort of high-risk (HR) myeloid malignancies (Kümpers, Koenecke et al.: BLOOD May 2008). The aim of this study was to validate our results in a larger cohort of patients. In contrast to our previous work we included different conditioning regimens as well as patients with Acute Myeloid Leukemia (AML) irrespective of their risk stratification according to cytogenetic (SWOG, ECOG criteria) and/ or mutational status (FLT3, NPM1). Circulating Ang-2 (in-house ELISA) was measured in serum of AML patients treated at our institution between 1991 and 2008 (n=191) immediately before standard (n=83) or reduced intensity conditioning (n= 104) for HSCT. Stem cell sources were BM (n=23), PBSC (n=163) or both (n=5) from MRD (n= 91), MMRD (n=7), MUD (n=67) and MMUD (n=26). The median age of the patients was 49 years (range 18–71). HSCT for AML (n=149) or secondary AML after MDS (n=42) was performed after primary induction failure (n=30) or for relapse (first relapse n=19, subsequent relapse n=5). 119 patients were transplanted in 1st CR; four in 2nd CR. 11 patients had no chemotherapy before HSCT. In this cohort, 114 of 159 evaluable patients suffered from HR-AML. Circulating pre-HSCT Ang-2 was elevated in patients (median (range): 1.7 (0.05–48.8) ng/ml) compared to healthy controls (0.92 (0.27–2.63) ng/ml; p<0.0001). Using univariate Cox regression analyses, patients’ age, conditioning regimen, remission status, cytogenetic/ mutational status, and Ang-2 were identified as prognostic variables. Multivariate Cox regression confirmed the independent prognostic impact of Ang-2 (hazard ratio 2.2, 95% CI 1.25–3.94, p = 0.007) and HR cytogenetics and/ or mutations (hazard ratio 1.5, 95% CI 1.09–2.11, p = 0.012) for Time to Relapse after HSCT. In this study we could show that Ang-2 is a valid and readily available biomarker to pre-estimate the risk of relapse in a large comprehensive HSCT cohort. Routine pre-HSCT measurement of Ang-2 may open new perspectives for riskadapted treatment of AML patients.