bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Peripheral Blood Stem Cell Mobilization and Harvest after Each Consolidation Chemotherapy in Patients with Acute Myeloid Leukemia in First Complete Remission Who Underwent Autologous Stem Cell Transplantation.
Authors: Shin Ho-Jin , Chung Joo Seop , Choi Young Jin , Lee Je-Jung , Sohn Sang Kyun , Cho Goon Jae , Kim Hyeoung-Joon , Yang Deok-Hwan , Back Jin Ho 
Published: April 2020

Abstract
Background: Peripheral blood stem cells (PBSC) are increasingly being used to restore hematopoiesis following high-dose chemotherapy in patients with acute myeloid leukemia (AML) without an HLA-matched related donor. However, which of consolidation-mobilization chemotherapy cycles are the most compatible in terms of the yield of progenitor cells and outcomes after autologous peripheral blood stem cell transplantation (APBSCT) has not been known.
Patients and methods: 49 mobilization procedures performed on 28 patients with AML who underwent APBSCT enrolled at three centers. The treatment protocols administered to patients with AML consisted of an induction chemotherapy in combination with cytarabine or BHAC plus idarubicin, and consolidation chemotherapy with high dose cytarabine (3 g/m2 iv bid, day 1, 3 and 5). In all patients, the collection of PBSC was performed during recovery after giving consolidation chemotherapy and granulocyte colony-stimulating factor (G-CSF).
Results: 28 AML patients in first complete remission (CR) underwent total 49 aphereses to obtain a minimum dose of 2×106/kg CD34+ cells/kg after each consolidation chemotherapy. First, second and third consolidation cycles were 17, 24 and 8, respectively. According to the total collected CD34+ cells ×106/kg, two main groups were considered that is, poor mobilizers (PM), with a collection of &lt; 2×106/kg, and good mobilizers (GM), with a collection of ≥ 2×106/kg. Of 49 consolidation cycles, 15/17 (88.23%), 16/24 (66.66%) and 3/8 (37.5%) were GM after 1st, 2nd and 3rd consolidation cycles, respectively (P=0.012). The median follow up was 22 months (range 3–59). PBSC mobilization after first plus second versus third consolidation chemotherapy that was used for APBSCT were compared. The 2-year disease-free survival (DFS) rate was 36.1% and 64.3% (P=0.161), and the 2-year overall survival (OS) rate was 34.9% and 80% (P=0.190). Patients who were infused with ≥ 2 ×106/kg CD34+ cells at APBSCT had a shorter DFS rate at 2 years, 25.0%, than those with &lt; 2 ×106/kg CD34+ cells, 53.8%. However, there were no significant differences between the two groups (P=0.169). Relapse rate after stem cells infusion which mobilized from first, first plus second, second and third consolidation cycles were 60% (3/5), 61.1% (11/18), 50% (4/8) and 2/6 (33.3%), respectively.
Conclusion: If reinfused CD34+ cells are adequate, the stem cells harvested after third consolidation chemotherapy may be the best source for APBSCT in view of relapse rate and DFS.
Use of Pharmacogenetics and Clinical Factors To Predict the Maintenance Dose of Warfarin.
Authors: Gage B. F. , Eby C. S. , Johnson J. A. , Rieder M. J. , Ridker P. M. , Rettie A. E. , Aquilante C. , Milligan P. E. , Marsh S. , Voora D. , Langaee T. , Veenstra D. L. , Birman-Deych E. , Glynn R. , Nickerson D. A. , McLeod H. L. 
Published: April 2020

Abstract
Background Initiation of warfarin therapy using trial-and-error dosing can cause bleeding. Clinical factors explain only 20%–30% of the variability in the therapeutic dose of warfarin. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene correlate with the clearance of S-warfarin and SNPs in the vitamin K epoxide reductase (VKORC1) gene predict warfarin sensitivity. We test the hypothesis that the combination of clinical and pharmacogenetic information can predict the therapeutic warfarin dose.
Methods We collected DNA, demographic variables, laboratory values, and medication histories from patients taking warfarin. Subjects either attended an outpatient anticoagulation clinic or participated in the PREVENT (prevention of venous thromboembolism) study. After PCR amplification, we used Pyrosequencing® to genotype DNA regions for 2 coding CYP2C9 SNPs, *2 (C430T) and *3 (A1075C), and for 4 noncoding VKORC1 SNPs: C861A, A5808C, G6853C, and G9041A. Using multiple regression, we quantified the association between therapeutic warfarin dose and clinical and genetic factors in a derivation cohort of 900 participants and a validation cohort of 100 participants.
Results The VKORC1 G6853C SNP was the first variable to enter the stepwise regression equation and was associated with a 27% decrease in the warfarin dose per allele in Caucasian patients. The VKORC1 A5808C SNP was associated with a 33% decrease per allele in warfarin dose in African-American patients. Other significant (p &lt; 0.05) predictors of the therapeutic warfarin dose, in order of entry into the regression equation and their effect on warfarin dose were: body surface area (+12% per SD increase), CYP2C9*3 (−33% per allele), CYP2C9*2 (−20% per allele), age (−7% per decade), target INR (+8% per 0.5 unit increase), amiodarone use (−24%), African-American race (+12%), smoker (+9%), and simvastatin or fluvastatin use (−5%). A dosing equation that included these pharmacogenetic and clinical factors explained 52% of the dose variability in derivation cohort and 55% of the variability in the validation cohort.
Conclusions The therapeutic warfarin dose can be estimated from clinical and pharmacogenetic factors that can be obtained when warfarin is started. Use of this dosing equation has potential to aid in the prediction of an optimal warfarin dose, which may decrease the risk of bleeding during the initiation of warfarin therapy.
Effective CD34+ Stem Cell Mobilization with Low-Dose Pegfilgrastim.
Authors: Gladstone Douglas E. , Stevens Michelle , Locher Emily , Zamkoff Kenneth W. , Hagag Nabil G. 
Published: April 2020

Abstract
Introduction: Numerous strategies utilizing chemotherapy followed by filgrastim allow for the successful mobilization of peripheral hematopoietic progenitor cells. To eliminate the need for self-administration of multiple growth factor injections and to minimize cost, we piloted a mobilization strategy consisting of low-dose Pegfilgrastim and chemotherapy.
Methods: Seven consecutive patients scheduled to undergo hematopoietic progenitor cell transplant for hematologic malignancy received a single 6mg injection of Pegfilgrastim 24–48 hours after chemotherapy. The targeted CD34+ collection was 5x106cells/ kg. The number of apheresis, CD34+ cell yield, time to engraftment and toxicities were recorded. These patients were compared to the 15 previous patients who received Filgrastim and chemotherapy for mobilization.
Results: In the pilot population, the median age was 60 (range: 39–67) years. Chemotherapy priming before Pegfilgrastin for three patients with multiple myeloma and two with stage IV mantle cell lymphoma was 4.5grams/m2 of cyclophosphamide; one patient with relapsed, stage IV Hodgkin’s disease received ICE and one multiple myeloma patient with a serum creatinine of 3.1mg/dL, received 2.5grams/m2 of cyclophosphamide. Five patients required a single apheresis, two patients required two apheresis collections. The median CD34+ yield was 6.7 x106/kg (range: 3.2–13.7). The median time to neutrophil engraftment was 10 days (range: 9–12). The median time from Pegfilgrastim to apheresis was 9 days (range: 7–10). The Pegfilgrastim cost per patient was $3,250.00. Toxicity was limited to grade II bone pain.
The comparison group consisted of seven multiple myeloma, four leukemia and four lymphoma patients. Their median age was 51.5 years (range: 24–67). The median number of apheresis procedures was 2 (range: 1–3). The median CD34+ yield was 5.6 x106/kg (range: 2.9–17.6). The median time to neutrophil engraftment was 11 days (range: 9–11). The median time from cytokine to apheresis was 8.5 days (range: 3–16). The median cost of Filgrastim per patient was $3,650.00 (range: $2,290–$8,760). The median number of Filgrastim injections was 10 (range: 10–14). Toxicity was limited to grade II bone pain.
Discussion: In a two cohorts of patients with hematologic malignancies Pegfilgrastim as compared to Filgrastim resulted in a decreased cytokine cost, a fewer number of apheresis collection procedures, a more predictable time to first apheresis and no self-administration of medication. There was no significant difference in the time to engraftment.
Conclusion: Low-dose Pegfilgrastim in conjunction with chemotherapy results in as effective CD34+ progenitor cell mobilization with less drug cost and apheresis time as compared to Filgrastim with chemotherapy.
Tandem Autotransplants’ Peripheral Blood Stem Cells Following Sequent High-Dose CHEOP Chemotherapy for Aggressive Lymphoma.
Authors: Luo Yi , Huang He , Cai Zhen , Lin Maofang 
Published: April 2020

Abstract
The majority of poor-risk lymphoma patients are not cured with conventional chemotherapy. There is evidence for superiority of single high-dose chemotherapy in such patients, but many still die from recurrent disease. Strategies to improve survival in these poor-risk patients include dose-intensification with high-dose chemotherapy and PBSC support autologous transplantation. These more aggressive strategies are feasible and tolerable. Whether tandem transplantation will prove more effective than current single high-dose therapy in appropriately selected patients remains to be determined. The purpose of this study was to evaluate the effectivity and safety of mobilization regimen, and the effectivity and tolerance of sequential chemotherapy combined with tandem autotransplant in aggressive lymphoma. In this study, the clinical data of 5 patients with recurrent, aggressive lymphoma treated with of sequential chemotherapy combined with tandem autotransplant were analysed respectively. The group included 1 HD and 4 NHL. Mobilization regimen was CHOEP combined with G-CSF (5ug•kg−1•d−1). The conditioning regimen for the tandem transplantation was high-dose CHEOP. The interval of the two autotransplantation was 9(5~31)weeks. In tandem autotransplant, the cell number of MNC which was transfused was 3.05 (ranged from 1.91~4.14) ×108 •kg−1 and 3.55 (ranged from 2.23~6.0) ×108•kg−1; CD34+ was 4.11 (ranged from 2.59~4.94) ×106•kg−1 and 5.70 (ranged from 2.77~10.6) ×106•kg−1; CFU-GM was 2.96 (ranged from 2.01~4.54) ×105•kg−1 and 2.44 (ranged from 1.78~2.9) ×105•kg−1 respectively (P&gt;0.05). All patients reached prompt and sustained hemotopoietic reconstitution. The interval of ANC ≥0.5×109/L was 10 days (ranged from 8~12) and 10.5 days (ranged from 9~12); Pt ≥2.0×109/L was 11 days (ranged from 10~14) and 12.5 days (ranged from 10~15) respectively (P&gt;0.05). Four patients were alive while 3 was in disease-free with median 46 (range 9~88) months. The overall survival was 80%, and the disease-free survival was 60%. In the conclusion, the method of sequential high-dose CHEOP chemotherapy combined with tandem autotransplant of peripheral blood stem cells for aggressive lymphoma is safe and effective.
Natural History of Relapse after Autologous Stem Cell Transplantation for Multiple Myeloma.
Authors: McClune Brian , Buadi Francis , Yunus Furhan , Minhas Sohail , Walsh William , Przepiorka Donna 
Published: April 2020

Abstract
Although autologous stem cell transplantation (APBSCT) is known to prolong survival of patients with myeloma, most patients relapse after transplantation. How treatment of patients who relapse after transplantation affects survival is not clear. At our institution, of 83 patients transplanted for myeloma from 1996–2005, we identified 25 patients who relapsed and had adequate records for analysis. The relapse cohort consisted of 15 single APBSCT and 10 tandem APBSCT recipients. Twenty patients were Stage III at time of original diagnosis, 3 patients were Stage II, and 3 were Stage I with 15 patients being IgG-kappa, 3 patients IgA-kappa, 2 patients IgG-lambda and 1 patients IgA-lambda. Two patients had non-secretory disease and 2 had light-chain only myeloma. Best response achieved after transplant included 5 complete responses (CR), 14 partial responses (PR), one stable disease (SD), 3 minimal responses (MR), and 2 with progressive disease (PD). Maintenance therapy consisting of interferon-alfa, pulse-dosed or every-other-day steroids, and thalidomide with or without steroids was documented in 12 patients. Of the relapsed cohort, 19 went on to receive further treatment consisting of radiation therapy (2), dexamethasone-based chemotherapy [bortezomib, another induction regimen, thalidomide] (15) or another transplant (2). The median duration of response for the relapse cohort was 372 days (76–1661 days). Median survival from relapse is 304 days (range 19–1155 days). There was a trend for a correlation between duration of initial response and survival after relapse (p=0.08), but no correlation with survival after relapse and best response to APBSCT (p=0.63), use of maintenance posttransplant (0.27) or treatment of relapse (0.17). The small number of patients may have limited the power of our study to detect significant associations in our cohort. We conclude that patients who relapse after APBSCT can have a prolonged survival, and those with the longest initial duration of response have the best outcome, but the optimal approach to salvage for these patients is not clear.
POEMS Syndrome: A Patient with an IgA lambda Plasma Cell Disease. Expression Levels of VEGF and bFGF Correlates with Clinical Course.
Authors: Schrader Carsten , Tiemann Markus , Zirrgiebel Ute , Guenther Andreas , Janssen Dirk , Kneba Michael , Gramatzki Martin 
Published: April 2020

Abstract
Purpose: POEMS syndrome is a rare disease characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes. We present a severely ill woman with a four year history of polyneuropathy showing all signs of a POEMS syndrome. Response to chemotherapy including high-dose melphalan treatment and autologous bone marrow transplantation was monitored and vascular endothelial growth factor (VEGF) as well as basic fibroblast growth factor (bFGF) levels were measured.
Methods: Blood investigation was done for serum electrophoresis analysis and analysis of VEGF, bFGF and IL-6 by ELISA. Bone marrow biopsy specimen was investigated immunohistochemically for kappa, lambda, alpha, gamma, CD20, CD56, Cyclin D1, VEGF.
Results: Immunohistochemical investigation of the bone marrow biopsy showed a infiltration of lambda and alpha positive plasma cells (10%). Only few plasma cells expressed kappa. The tumor cell were negative for CD20, CD56 and Cyclin D1, but positive for VEGF in line with the high VEGF levels in the blood. Blood investigation revealed a discrete monoclonal gammopathy of IgA lambda type. Initially, high levels of VEGF (1468.7 pg/ml) and bFGF (112.9 pg/ml) were detected. However, treatment with high-dose melphalan and tandem autologous bone marrow transplantation proved extremely helpful in symptom control. Already after the first transplant the patient started to walk again and lost pulmonary hypertension. In parallel VEGF and bFGF levels decreased and the performance status of the patient improved dramatically.
Conclusion: VEGF and bFGF measurement is a useful tool for monitoring disease activity in POEMS syndrome. Bone marrow transplantation is an important therapy also in severely ill patients.
Idiotype TCR Vβ2 DNA Plasmid Constructe, Transfer and Express in K562 Cells.
Authors: Zhou Yubing , Huang Meijuan , Yang Lijian , Chen Shaohua , Wu Xiuli , Li Yangqiu 
Published: April 2020

Abstract
Recently, combination of different therapeutic strategies have significantly increased survival in patients with hematologic malignancies. Specific immunotherapy is an important anticancer therapy to eradicate minimal residual disease in leukemia patients after chemotherapy or stem cells transplantation. DNA vaccines have been showed to induce strong and persistent cell-mediated and humoral immune responses and used in Hodgkin lymphoma patients, using the idotype Ig antigen. In order to develop the anti-lymphoblastic leukemia idiotypic TCR DNA vaccine, which was expected to induce the specific immune response anti T-cell lymphoblastic lymphoma /leukemia in vivo. The rearranged idiotypic CDR3 fragment coding TCR Vβ2, which was identified from a TCR Vβ2 clone-Molt4 cell line, was amplified using RT-PCR, and the PCR products were then cloned into pIRES vector. The recombinant plasmids contaning target gene (405 bp, 135 peptides) were analyzed by digestion with restriction enzyme (EcoRI and XbaI), PCR and sequencing. The correct fragment was transfected into K562 cells. The condition of idiotypic protein expression was tested by indirect immunophenotyping fluorescein dyeing with anti-TCR Vβ2 monoclonal antibody, SDS-PAGE and Western-Blot. The results showed that the recombinant DNA plasmids, pIRES-Molt4 Vβ2, containing idiotypic TCR Vβ2 frgments of the Molt4 cell line were developed successfully. A 15 KD protain which can bind with TCR Vβ2 antibody specially were identified from pIRES-Molt4 Vβ2 transduced K562 cells, indicating that can express special TCR Vβ2 protain in vitro. It should be further demonstrated whether the idiotype protein can elicit both humoral and cellular immune response for anit Vβ2+ leukemic cells in vivo.
Interaction of Measles Virus Vectors with Auger Electron Emitting Radioisotopes.
Authors: Dingli David , Peng Kah-Whye , Harvey Mary E. , Vongpunsawad Sompong , Bergert Elizabeth R. , Kyle Robert A. , Cattaneo Roberto , Morris John C. , Russell Stephen J. 
Published: April 2020

Abstract
Background: Viral vectors based on the Edmonston strain of measles virus (MV-Edm) selectively destroy all tumor cell lines tested in vitro. The oncolytic activity of the virus is enhanced by expression of the thyroidal sodium iodide symporter (MV-NIS) that allows selective 131I uptake by infected tumor cells and eliminates myeloma tumor xenografts that are resistant to the parent virus. MV-NIS is being considered for therapy of patients with relapsed or refractory multiple myeloma. Advanced myeloma is associated with significant immunosuppression with the potential risk of uncontrolled virus proliferation. The number of agents with activity against MV is limited. Low energy (Auger) electrons have a short path length and selectively damage cells in which the isotope decays. Thus, we hypothesized that the Auger electron emitting isotope 125I, selectively taken up by cells expressing NIS, can be used to control viral proliferation.
Methods: A replication competent MV that expressed both a soluble form of carcinoembryonic antigen (CEA) and NIS (MV-NICE) was rescued and characterized. Cells were infected with MV-NICE or control vectors and exposed to 125I with appropriate controls. CEA expression and viral titers were determined at different time points. The role of free radical generation on virus replication was explored. In vivo control of MV-NICE replication with 125I was attempted.
Results: MV-NICE replication in vitro is inhibited by the selective uptake of 125I by cells expressing NIS. Extracellular decay of the isotope has no effect on virus proliferation. Auger electron damage is in part mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125I was not possible under the conditions of the experiment.
Conclusion: MV-NICE does not replicate faster in the presence of radiation under our experimental conditions. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo.
Automated Retroviral Insertion Site Sequence Analysis and Mapping Tool Followed by Database Analysis.
Authors: Laufs Stephanie , Giordano Frank A. , Hotz-Wagenblatt Agnes , Appelt Uwe , Lauterborn Daniel , Fellenberg Kurt , Zeller W. Jens , Fruehauf Stefan 
Published: April 2020

Abstract
Increasing use of retroviral vector-mediated gene transfer and recent reports on insertional mutagenesis in mice and humans created intense interest to characterize vector integrations on the genomic level. Techniques to determine insertion sites, mainly based on time consuming manual data processing and compilation, are thus commonly applied in gene therapy laboratories. Since a high variability in processing methods hampers further data comparison, there is an urgent need to systematically process the data arising from such analysis.
The obtained sequences from the integration site analysis are judged to be authentic only if the matching part of the genomic query sequence is surrounded by the 5′LTR-sequence on the one side and the adapter-sequence on the other side. Therefore we developed an Integrationseq tool. In this task, different methods for converting the ABI sequence trace files to high quality sequences and for recognizing and deleting the LTR and adaptor parts of the isolated clones were implemented. If neither a primer nor a LTR could be found, the sequence is discarded. If the LTR is found on the complementary strand, the integration sequence is reversed. The remaining sequence between primer and LTR positions are taken as the n integration sequence and written to a sequence output file.
We validated the Integrationseq tool using 259 trace files originating from integration site analysis (LM-PCR). Sequences can be trimmed by IntegrationSeq, leading to an increased yield of valid integration sequence detection, which has shown to be more sensitive (100%) than conventional analysis (94.3%) and 15 times faster than conventional analysis, while the specifities are equal (both 100%). Valid integration sequences get further processed with IntegrationMap for automatic genomic mapping. IntegrationMap runs 50 times faster than conventional methods and retrieves detailed information about whether integrations are located in or close to genes, the name of the gene, the exact localization in the transcriptional units and further parameters like the distance from the transcription start site to the integration. Further information, e.g. data about CpG-Islands, LINEs or SINEs, and their distances to the integration is also displayed. Output files generated by the task were found to be 99.8% identical with results retrieved by conventional mapping with the Ensembl alignment tool.
Using both tools, IntegrationSeq and IntegrationMap, a validated, fast and standardized high-throughput analysis of insertion sites can be achieved for the first time.