bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Erythropoietin (EPO) in Children with Malignancies.
Authors: Kovacs Gabor T. , Muller Judit , Csoka Monika , Vonnak Eszter , Erlaky Hajna , Farkas Andrea , Somlai Agnes , Fekete Gyorgy 
Published: October 2019

Abstract
Recombinant erythropoietin is widely used for the treatment of anemia in malignant diseases in adults. There are only limited data of its use in pediatric population.
In this study we analysed the effectiveness and tolerability of recombinant human erythropoietin (NeoRecormon) in children with malignant diseases.
80 children with malignant diseases were analysed. 40 patients (15 girls, 25 boys) received EPO in a mean dosage of 144.5±14.1 IU/kg three times a week. The mean age of the EPO-treated patients was 8.8 (2.5–16) years. 26 children had acute lymphoblastic leukemia and 14 patients had solid tumor. Match-paired, retrospective control patients (n=40) with similar diagnosis were used for the data analysis as control group (C).
The mean duration of EPO treatment was 5.8 months (3–8 mo). In 6 patients the therapy was ceased due to elevated serum hemoglobin (Hb) (>130 g/L), in 6 patients the dose was increased up to 200 IU/kg three times a week, and 5 patients discontinued the therapy (2 died, 3 unsuccessful treatment). The mean amount of erythrocyte transfusion in the first 3 months of chemotherapy (CT) was 4.1±3.1 U/patient in the EPO group, and 8.0±4.2 in C, and during 6 months of CT 4.5±3.4 with EPO, and 11.6±7.1 in C (p<0.05).
Soluble transferrine receptor (STFR) levels in serum increased in the EPO group after 2 weeks of therapy from 3.2±2.0 up to 4.8±2.9 (p<0.05). In general in 26/40 patients a significant elevation of the Hb levels and decrease of the need of erythrocyte transfusions could be detected. In 22 patients the STFR levels increased more than 50 % after 2 weeks of therapy. In this subgroup 18/22 children responded to EPO therapy. All patients tolerated the therapy well, no severe side effects were detected. In summary, EPO treatment is effective in about 2/3 of pediatric oncology patients. The therapy is well-tolerated. Increase in the STFR serum levels might be a useful marker for the effectiveness of EPO in children.
Clinical and Immunological Activity of WT1 Peptide Vaccination in Patients with Acute Myeloid Leukemia and Myelodysplasia: Results of a Phase II Trial.
Authors: Keilholz Ulrich , Letsch Anne , Busse Antonia , Asemissen Anne M. , Schmittel Alexander , Hofmann Wolf K. , Uharek Lutz , Blau Igor W. , Thiel Eckhard , Scheibenbogen Carmen 
Published: October 2019

Abstract
The transcription factor Wilms tumor protein (WT) 1 belongs to a new generation of tumor antigens, which are essential for tumor cell proliferation. WT1 is highly expressed in AML and in MDS upon appearance of blasts. A phase II trial of vaccination with the HLA-A2-restricted WT1.126–134 peptide was performed in patients with AML and MDS and overexpression of WT1 to determine immunogenicity and clinical activity. Patients received vaccinations with 0.2 mg WT1.126–134 peptide (day 3), 62.5 mcg dendritic cell-stimulating adjuvant GM-CSF (days 1–4) and 1 mg T helper protein keyhole limpet hemocyanin (day 3). The initial 13 patients were to receive 4 biweekly and subsequent 4-weekly vaccinations, the subsequent 13 patients were continuously vaccinated biweekly. Vaccination was continued in absence of overt disease progression. WT1 levels were assessed by quantitative RT-PCR and WT1-specific T cell responses by tetramer analyses and cytokine flow cytometry. Response assessment following IWG-MDS criteria was used, capturing stable disease and hematologic improvement. A duration of 8 weeks was required for stable disease. Enrolment was completed in June 2006 with 24 patients with AML and 2 with MDS (RAEB). Of the 24 AML patients, 16 had > 5% marrow blasts at study onset (8 without prior chemotherapy, 4 with disease persistence following chemotherapy, 4 with PR), and 8 were in CR at high risk for relapse. A median of 10 (range 4 – 23) vaccinations was administered with 8 patients currently still under treatment. No significant toxicity occurred. To date, 22 patients are evaluable for clinical response. Overall, 8/16 patients with > 5% marrow blasts at study onset displayed clinical efficacy of vaccine treatment (SD or better). One AML patient achieved CR for 12 months after brief initial progression, and 7 patients had disease stabilization (2, 2+, 3, 3, 6, 10+, 14 months). One of these patients with RAEBII had a major response of neutrophils and platelets, and one AML patient had initial progression and subsequent transient complete clearance of peripheral blasts. WT1 transcripts as molecular disease marker decreased at least 3-fold (range 3-fold - >50-fold, median >10-fold) in 12 of 20 currently evaluated patients, including all 8 patients with evidence of clinical efficacy and 4 of 5 AML patients vaccinated in CR. The generation of a WT1-specific T cell response in peripheral blood and bone marrow was detected in 12 of 16 evaluated patients including all 6 of these 16 patients with evidence for clinical efficacy. This study shows that WT1 vaccination has promising antileukemia activity. A multicenter comparative WT1 vaccination study in CR patients at high risk of relapse is currently initiated.
A Phase II Randomized, Double-Blind, Eight-Arm, Parallel-Group, Dose-Response Study of Apixaban, a New Oral Factor Xa Inhibitor for the Prevention of Deep Vein Thrombosis in Knee Replacement Surgery - On Behalf of the Apixaban Investigators.
Authors: Lassen Michael R. , Davidson Bruce L. , Gallus Alexander , Pineo Graham , Ansell Jack , Deitchman David 
Published: October 2019

Abstract
Background: Apixaban is an orally active, highly selective, reversible inhibitor of Factor Xa. It binds directly to the active site of Factor Xa without requiring anti-thrombin. Antithrombotic activity was evaluated in a dose-ranging study in patients undergoing total knee replacement.
Methods: Patients were allocated randomly to 1 of 6 double-blind doses of apixaban (5, 10, or 20 mg) given as a single or a twice-daily divided dose, or enoxaparin 30 mg bid, or open-label warfarin titrated to an INR of 1.8–3.0. Apixaban and enoxaparin were started 12 to 24 hours after completing surgery; warfarin the evening of the day of surgery. Treatment continued for 10–14 days. Mandatory bilateral venography was performed at the end of treatment. Patients could then be treated with non-study drug prophylaxis according to the attending physician’s discretion. All patients were seen at follow-up on day 42. The primary efficacy outcome was a composite of all venous thromboembolic events (VTE) comprising asymptomatic and symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) and all-cause death during the treatment period. A central independent committee whose members were unaware of treatment assignments adjudicated all efficacy outcomes and bleeding events.
Results: Of 1217 subjects treated and included in the safety analysis, 856 were eligible for the efficacy analysis. The composite VTE plus all cause death rate in the apixaban groups combined was significantly lower than the rate in the enoxaparin (p<.02) and warfarin (<.001) groups (8.6%; 15.6%; 26.6%, respectively). A trend for a dose-related decrease (p=.09) in the composite VTE plus all cause death rates of 10.6%, 8.6%, and 6.8% was apparent when QD and BID apixaban doses were combined as total daily doses of 5, 10, and 20 mg, respectively. When QD and BID apixaban doses were assessed separately, dose-dependent decreases in the composite VTE plus all cause death rates were observed for each but did not reach statistical significance. The composite VTE plus all cause death rates for apixaban 2.5 mg BID and 5 mg QD were 9.9% (95% CI:5.1–17.0) and 11.3% (95% CI:5.8–19.4) respectively, compared with a rate of 15.6% (95% CI: 9.4–23.8) in the enoxaparin group. For the composite outcome of proximal DVT+PE+all-cause death, each apixaban group had a lower event rate (0–2.7%) than the enoxaparin rate (4.6%). The incidence of major bleeding for apixaban ranged from 0.0% (2.5 mg BID) to 3.3% (20 mg QD); no major bleeding was observed in either the enoxaparin or warfarin groups
Conclusions: Apixaban, an oral Factor Xa inhibitor, demonstrates a favorable efficacy and an acceptable bleeding safety profile at doses of 5 to 20 mg per day in the prevention of VTE after knee replacement surgery.
Prestorage Leukoreduction of Transfused Red Cells Is Associated with Significant Ongoing 2–12 Month Survival Benefit in Cardiac Surgery Patients.
Authors: Boshkov Lynn , Chien Grace , VanWinkle Donna , Furnary Antony P. , Wu Yingxing , Grunkemeier Gary , Morris Cynthia D. 
Published: October 2019

Abstract
Introduction: Red cell (RBC) transfusion (vs no transfusion) in cardiac surgery is associated with higer operative mortality and shortened long-term survival. Studies have suggested use of leukoreduced RBCs vs standard RBCs in transfused cardiac surgery patients is associated with improved short term (60 day) survival. It is unclear if this benefit persists longer term. Study Aim: This prospective, randomized, double-blind, 3-center trial compared short term and intermediate-term mortality (2–12 mos) in adult cardiac surgery patients undergoing cardiopulmonary bypass (CPB) randomized to receive either prestorage leukoreduced RBCs (LR-RBCs) vs standard RBCs (S-RBCs)
Methods: 1226 cardiac surgery patients (undergoing coronary artery bypass grafting, cardiac valve replacement, or a combination of the two) were pre-operatively randomized to receive either LR- or S-RBCs. Patients were operated on by the same group of surgeons. Patients and clinicians were blinded as to product type. All deaths were verified by National Death Index records.
Results: 562 patients (45.8%) were transfused: 304 received LR-RBCs and 258 S-RBCs. Groups were statistically equivalent demographically and by all Society of Thoracic Surgery risk criteria. Operative mortality was not affected. However a survival benefit for the LR-RBC group was evident at 60 days which persisted for 12 months (see Table 1). Mortality for non-transfused patients was significantly lower than for patients receiving either LR- or S-RBCs at all time points (p<0.0001).
Conclusion: In adult cardiac surgery patients undergoing CPB who require transfusion, use of LR-RBCs vs S-RBCs is associated with significant improvement in survival at 2 months, and this survival advantage persists for up to 1 year.
Table 1: Percent (%) Mortality--Operative (Op) and Cumulative by Month (mo) Post-operative Op 2 mo 4 mo 6 mo* 9 mo* 12 mo* *Kaplan-Meier (KM) analysis LD-RBCs 4.9 4.9 5.3 5.9 5.9 7.0 S-RBCs 7.0 9.7 9.7 10.1 11.3 11.7 p-value 0.305 0.029 0.044 0.070 0.025 0.053
Modification of Anemia Parameters after Blood Transfusion.
Authors: Berz David , Singh Himani , McCormack Elise , Mazur Eric 
Published: October 2019

Abstract
Background: Optimally the necessary laboratory evaluation for the diagnosis of the underlying causes for anemia is done before blood transfusion. However, clinical and logistical demands often mandate the transfusion of packed red blood cells before all the necessary parameters are obtained. It is poorly defined which impact transfusion has on the parameters necessary for the diagnosis of the underlying anemia cause. We conducted a prospective study to investigate the effect of the transfusion of two units packed red blood cells on lactate dehydrogenase(LDH), ferritin, transferrin, haptoglobin, total iron binding capacity(TIBC), folate, cyanocobalamine(B12), hemoglobin, MCV and hematocrit by measuring those tests before and at 6, 12, 24 and 48 hrs after transfusion. Patients and
Methods: We included nineteen normovolemic, not actively bleeding consecutive patients; six of whom were diagnosed with anemia of chronic disease, one MDS and twelve iron deficiency anemias. Acutely bleeding patients, patients not able to give informed consent, prisoners under hospitalization and patients younger than 18 years old were excluded. All patients received transfusion of two units of packed red blood cells. The statistical analysis was performed using a repeated measurement ANOVA algorithm.
Results: The transfusion of two units of packed red blood cells did not result in a significant change of ferritin, transferrin, haptoglobin, cyanocobalamin and lactate dehydrogenase throughout the observation period. Hemoglobin, MCV and hematocrit demonstrated an early change and equilibration without significant change after the first six hours post transfusion. Serum iron levels were transiently elevated in the severely iron deficient population, but returned back to baseline after 24hrs. Folate experienced a statistically significant, persistent change in the posttransfusion period. For the first 48 hrs post transfusion the following conclusions were made: First, the diagnosis of iron deficiency or chronic disease anemia is not confounded by blood transfusion, particularly when using ferritin as the predominant diagnostic parameter. Second, the diagnosis of hemolytic anemias, using haptoglobin and LDH is not interfered by transfusion of two units of packed red blood cells. Third, vitamin B12 deficiency can be diagnosed after transfusion, whilst folate deficiency on the base of red blood cell folate cannot.
Classification and Survival of 179 Patients with T- and NK-Cell Lymphomas at the Federal Research Hematology Center of Russian Academy of Medical Sciences: A Retrospective Study.
Authors: Vinogradova Yulia E. , Lutsenko I.N. , Samoilova R.S. , Kaplanskaya I.B. , Vorobiev Ivan A. , Zingerman Boris V. , Rijicova N.B. , Shklovskiy-Kordi Nikita E. , Giliazitdinova E.A. , Margolin Oleg V. , Maryin D.C. , Krementskaya Alexandra , Kravchenko S.K. , Varticovski Lyuba , Vorobiev Andrei I. 
Published: October 2019

Abstract
Introduction: According to the new WHO classification for Non-Hodgkin’s lymphomas developed in 2001, the diagnosis of many lymphoma patients has to be reevaluated. The existing information on therapeutic options for patients with these rare malignancies prior to development of WHO classification has been unreliable. The T-cell malignancies are associated with poor outcome, and it is important to identify patients that could benefit from novel intensive therapies.
Materials and Methods: We conducted retrospective analysis of patients with T- and NK-cell malignancies treated from 2000–2006 at the Federal Research Hematology Center of Russian Academy of Medical Sciences. The purpose of this study was to determine the frequency, clincopathological features, and outcomes of patients in predominantly Slavic population (European part of Russia).
Results: Because these malignancies present in a variety of nosological forms and their response to standard therapies is poor, multiple therapeutic regimens were employed as expected. Information on 151 patients with complete clinical and pathologic information that allowed appropriate diagnosis according to the WHO criteria was available for the analysis. Analysis of 188 patients required changes from the initial diagnosis after additional laboratory investigation: 25 cases (13.3%) previously considered to be T-cell lymphomas were excluded from the analysis, mostly because of an inadequate histopathological material. Similar to previously reported data, a significant number of T- and NK- cell lymphomas (12.4%) were excluded as compared to B-cell (3.1%) lymphomas, which emphasizes the difficulties in diagnosis of mature T- and NK-cell lymphomas. Twelve out of 163 patients with verified T-cell lymphomas after correction of diagnosis were treated and observed in other countries or regions, and were also excluded from the final analysis. The only difference in 151 remaining patients was an increased incidence of T-cell malignancies with mediastinal involvement, with overall survival similar to those reported elsewhere. Final analysis of 28 additional cases in 2006 for a total of 179 patients will be presented.
Conclusions: Our survey of patients with T-cell malignancies represents a systematic analysis of these rare malignancies and establishes the communality of clinical features and response to therapies.
Kaplan-Mayer Survival of all TCL Kaplan-Mayer Survival of all TCL
Leukemia-Derived Fibroblast Cells Produce Vascular Endothelial Growth Factor Significantly in Chronic Myelogenous Leukemia Cases.
Authors: Shirasaki Ryosuke , Tashiro Haruko , Noguchi Mitsuho , Kawasugi Kazuo , Shirafuji Naoki 
Published: October 2019

Abstract
Objective: We reported recently that myofibroblast cells in bone marrow cells of chronic myelogenous leukemia (CML)-patients were partly derived from CML clone, which was identified after long-term bone marrow cell-cultures. The generated BCR-ABL-positive fibroblast cells produced various kinds of cytokines more than that observed in the normal clone-derived fibroblast cells. Among these cytokines, we focus on vascular endothelial growth factor (VEGF)-system in this report.
Materials and Methods: Bone marrow cells were collected from chronic myelogenous leukemia cases (20 of chronic phase (CP), 3 of accelerated phase (AP), 8 of blast crisis phase (BC)), which were separated with gravity sedimentation. Obtained non-adherent mononuclear cells were cultured in DMEM with 10% FCS in the humidified 5% CO2 incubator. When cells showed morphological changes into fibroblastoid cells, cells were treated with trypsin and further cultured. The obtained stromal fibroblast cells were sub-cloned into culturing in 96 well plates, and from which RNAs were extracted. cDNAs were synthesized, and RT-PCR was performed to identify BCR-ABL fusion product. The selected clones were further analyzed on DNA levels with FISH to identify BCR-ABL. The concentration of VEGF in the patients’ sera and in the conditioned media of non-adherent mononuclear cells, of fibroblast cells derived from normal clone and of fibroblast cells with BCR-ABL was measured with ELISA kit (R&D Systems). The expression of VEGF, VEGF receptor type-1 and VEGF receptor type-2 was also compared at RNA levels. The effect of anti-VEGF antibody to the culturing CML cells was determined using 3H-incorporation assay system.
Results and Discussion: The levels of VEGF in sera from CML patients were elevated significantly. However, in patients with CP the expression of VEGF was not observed in non-adherent mononuclear cells. In contrast, VEGF production was observed in non-adherent mononuclear cells from the patients with AP and BC. Stromal fibroblasts produced VEGF in CP, AP and BC, in which BCR-ABL-positive fibroblast cells produced at the significant levels. The expression of VEGFR-1 and -2 was detected in non-adherent mononuclear cells from CP, AP and BC. When non-adherent mononuclear cells from CML patients were cultured onto the stromal fibroblast cells, significant additive effects were observed with 3H-thymidine incorporation assays. And when anti VEGF antibody was added to the cultures, the proliferation activity was significantly decreased. These observations indicate that in CML cases, especially in CP, VEGF plays an important role for the cellular proliferation with paracrine system.
Development of Renal Calculi and Imatinib Therapy in CML: Is There an Association?.
Authors: Saikia Tapan , Hazarika Nandini , Dhabhar Boman 
Published: October 2019

Abstract
Reports are accumulating regarding the altered bone and mineral metabolism caused by imatinib (IM) therapy (Berman E, et al 2006 NEJM). This probably occurs through in vivo inhibition of PDGF receptors. It has been proposed that prolonged use of IM may cause some potentially serious metabolic pathological disorders. Compensatory rise in parathyroid hormone level may cause renal pathologies in these patients. In this observational study we came across a few patients on imatinib therapy for CML who experienced prolonged dyspepsia, abdominal and bone pain (suggestive of groans, moans, bones and stones features) and abdominal ultrasonography revealed renal calculi. This has led to collection of clinical data. So far, no systematic evaluation with radiological or biochemical have been undertaken in our cohort of 177 of CML on imatinib therapy. At the time of this report we have noted development of renal calculi (all symptomatic) in 7 patients of CML on imatinib therapy. All these patients have been on imatinib therapy 400 mg daily for more than 1 month before symptoms developed. In all but one, no surgical intervention has been necessary so far. Biochemical evaluation for altered bone metabolism revealed hyperphosphatemia in one and normal in another. Analysis of renal stone in one showed a composition of calcium phosphate and oxalate. Imatinib was not discontinued but reduced to 300 mg in 3 patients. It is possible that prolonged use of IM may alter calcium and phosphate metabolism leading to renal calculi formation. The proposed mechanisms could be,
interference with bone and mineral metabolism coupled with parathyroid dysfunction which in turn leads to renal tubular abnormalities or availability of excess oxalate for intestinal absorption brought about by low calcium ingestion.
Well designed cohort studies may throw more light in this area.
The Effect of CAHB on Myelodysplastic Syndrome In Vitro and Its Application in a Prospective Clinical Trial.
Authors: Cai Zhen , He Jingsong , Shi Jiming , Li Li , Han Xiaoyan , Guo Qunyi , Zhou Hui , Zhang Buwen , Huang He , Lin Maofang 
Published: October 2019

Abstract
Introduction: Despite recent advances, myelodysplastic syndrome (MDS) is still a therapeutic challenge. CAHB is a novel differentiation inducer which showed early evidence of efficacy in a phase I clinical trial. We used this agent to treat cultured MDS cells in vitro in our research laboratory and then, in a prospective clinical trial in our clinic. Preclinical data: We first investigated the effect of CAHB in vitro in human MDS-RAEB cell line MUTZ-1 cells. Treatment with CAHB remarkably inhibited the growth of MUTZ-1 cells in a dose-dependent and time-dependent manner with IC50 at 5.6 mmol/L at 48 hours. CAHB treatment decreased S phase cells, increased G2/M phase cells, but did not change G0/G1 phase cells, which indicated arrest in G2 phase. When treated with different concentrations of CAHB (0, 2.5, 5, 10 mmol/L) for 24 hours, the expressions of survivin mRNA decreased in a dose-dependent fashion.
Patients and method: Eligible patients with MDS had organ functions and were without significant cormobidities. Data from 3 pancytopenic patients on this trial were analyzed. Their whole blood counts were 1.1, 2.3, and 2.5 k/uL, respectively. Their hemoglobins were 7, 9, and 7 g/dL, respectively. Their platelets counts were 10, 31, and 20 k/uL, respectively. The blasts form all 3 patients were of myeloid immunophenotype and diploid chromosomal karyotype. All 3 patients received 0.45g/m2 CAHB for eight hours daily for 10 days every 5 weeks as 1 cycle. Clinical
Results: Upon the completion of the two courses, all had fatigue. Their bone marrow blasts decreased from 13.5% to7% (48% decrease), 26.5% to12% (55% decrease), and 11% to 2% (82% decrease), respectively. No grade 3–4 toxicities were observed after 2 months. Grade 1–2 toxicities included nausea and vomiting. Two patients had EKG changes with ST-segment depressions, u wave and bundle branch block which disappeared after the drug was stopped. There was no significant change in the peripheral blood cell counts in all 3 patients.
Conclusion: CAHB inhibited cell growth and induced apoptosis of MUTZ-1 cells in vitro. CAHB reduced blast cells in 3 MDS patients. Two patients had transient EKG changes. Our preliminary clincial data showed early evidence of efficacy of CHAB in treating MDS with a tolerable toxicity profile. Its mechnism of action is under further investigation.