bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Conditioning Regimens with or without Total Body Irradiation in Bone Marrow Transplantation from an Alternative Donor.
Authors: Yabe Hiromasa , Kato Shunichi , Yabe Miharu , Kudo Kazuko , Yagasaki Hiroshi , Horibe Keizo , Yamamoto Masuji , Ohara Akira , Kuroki Fumiko , Tsukimoto Ichiro , Kojima Seiji 
Published: October 2019

Abstract
An optimum conditioning regimen is indispensable in improving outcomes for patients with acquired aplastic anemia (AA) who receive bone marrow transplantation (BMT) from an alternative donor. Although high-dose total body irradiation (TBI) is effective in enhancing engraftment, intensive conditioning regimens are associated with increased regimen-related toxicity, which results in a decreased success rate. Currently, two different approaches are primarily used; a conditioning regimen including low-dose TBI and a fludarabin-based regimen without TBI. We attempt to clarify the efficacy and regimen-related toxicity of these two approaches. Ten patients (7 males, 3 females; median age 12y; range 9–17y) underwent an alternative donor transplant following a conditioning regimen with low-dose TBI (TBI group); patients received cyclophosphamide (50 mg/kg/d on days −5 to −2), antithymocyte globulin (Thymoglobulin, 2.5 mg/kg/d on days −5 to −2) and TBI (2.5 Gy x 2 on day −1). The donor was unrelated in 9 patients (3 were serologically HLA A or B antigen mismatched; 3 were serologically HLA DR antigen mismatched, 1 was both serologically and genotypically DR antigen mismatched; 1 was genotypically DRB1 mismatched; 1 was a genotypically complete match) and was a family member in 1 patient (serologically HLA A-mismatched father). Twelve patients (6 males, 6 females; median age, 11 y; range 2–20 y) received a conditioning regimen of fludarabine (25 mg/kg/d on days −5 to −2), cyclophosphamide (750 mg/m 2 /d on days −5 to −2), thymoglobulin (1.5 mg/kg/d on days −5 to −2) and thoracoabdominal irradiation (TAI, 3Gy x 1 on day −1) (TAI group). The donor was unrelated in 11 patients (8 were genotypically complete matches, and 3 were genotypically DRB1 antigen mismatched) and a family member in 1 patient (3 antigen-mismatched mother). The source of stem cells was unmanipulated bone marrow. Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus (0.02 mg/kg from day −1) and short-term methotrexate. Rejection was seen in one patient in each group. The doses of infused nucleated marrow cells were less than 2.0 x 10 8 /kg in both patients, and both patients then received a second transplant and achieved full donor chimerism. Acute GVHD grade II-IV developed in 2/10 evaluable patients in the TBI group and in 3/12 patients in the TAI group. Chronic GVHD developed in 5/9 evaluable patients in TBI group and 3/10 evaluable patients in TAI group. Median follow up was 9 months (4–27 months) in the TBI group and 21 months (3–33 months) in the TAI group. Both conditioning regimens were well tolerated and effective even in HLA-mismatched unrelated donor transplantation. Long-term follow up is warranted in order to compare the late sequelae in both regimens.
Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.
Authors: Kroeger Nicolaus , Brand Ronald , Martino Rodrigo , Guardiola Philippe , van Biezen Anja , Zander Axel , Niederwieser Dietger , De Witte Theo 
Published: October 2019

Abstract
We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %).
In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.
Addition of Purine Analogues to Induction/Consolidation Regimen Does Not Impair Peripheral Blood Stem Cell Mobilization and Bone Marrow Harvest for Autotransplantation in Acute Myeloid Leukemia.
Authors: Holowiecki Jerzy , Grosicki Sebastian , Hellmann Andrzej , Skotnicki Aleksander , Jedrzejczak Wieslaw W. , Dmoszynska Anna , Marianska Bozena , Robak Tadeusz , Giebel Sebastian , Wojnar Jerzy , Krawczyk-Kulis Malgorzata , Wojciechowska Maria 
Published: October 2019

Abstract
In the previous study by the Polish Adult Leukemia Group (PALG 1999 Study) we demonstrated that addition of cladribine to standard daunorubicine + cytarabine (DA-7) induction potentiates antileukemic activity of the regimen in acute myeloid leukemia (AML). However, there is a concern that the treatment with purine analogues may affect a successful collection of hematopoietic cells for transplantation (autoHCT).
The goal of this study was to compare the efficacy of peripheral blood and bone marrow hematopoietic CD34+ cell harvest in patients who both in induction and consolidation were treated with or without purine analogues and who were intended for autoHCT.
Sixty-seven AML patients, aged 41 (17–58) years, were included in this study; 33 patients received cladribine-containing regimen (DAC-7), one patient - fludarabine-containing regimen (DAF-7), 33 patients received standard treatment (DA-7, HAM, HD cytarabine). In the DAC-7 treated patients cladribine was also given as a adjunct to second HD cytarabine consolidation. AutoHCT using bone marrow (autoBMT) or peripheral blood (autoBCT) as a source of hematopoietic cells was performed in first complete remission after completion of consolidation therapy. An additional course of AraC 2x2g/m2 on days 1, 3, 5 + G-CSF 10 mg/kg since day 7 was used as mobilization in case of autoBCT.
The number of collected CD34+cells/kg was similar for patients pre-traeted with purine analogues and those not receiving purine analogues: 2.55 (0,79-9,25) x106/kg vs 2.5 (1,41–23,5) x106/kg (p=NS) for peripheral blood and 1.62 (0,32–3,01) x106/kg vs 1.55 (0,5–2,45) x106/kg (p=NS) for bone marrow, respectively. In 90% and 95% of patients for both subgroups sufficient number of hematopoietic cells for transplantation could not be collected (p=NS). The proportion of unsuccessful bone marrow harvest was significantly lower for patients pre-treated purine analogues with purine analogues compared to those not receiving purine analogues (90% vs 56%, p=0,04), wheras not difference was found with respect to peripheral blood cell collection (95% vs 62%, p=NS). All patients who received autoHCT engrafted. The time to neutrophil and platelet recovery was similar for both study subgroups.
We conclude that treatment with purine analogues in course of induction/consolidation therapy does not impair the hematopoietic cell harvest and does not decrease a chance to perform autoBCT or autoBMT in AML patients.
Mel-140 and TBI vs Mel-200 Prior to Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma - a Single Institution Experience.
Authors: Janakiraman Nalini , Chamarthy UshaSree , Acharya Radhika , Donthireddy Vijaya , Kamboj Ginny , Oja-Tebbe Nancy , Divine George 
Published: October 2019

Abstract
Between 1991–98, twenty-nine patients with myeloma received Mel-140 and TBI (960 cGy) followed by Cytoxan mobilized autologous PBSCT. Between 1998 and April, 2004, 41 patients received Mel-200 alone followed by autologous PBSCT. The two groups were comparable regarding age, gender, stage, number of prior regimens and ß2 microglobulin at diagnosis. However, the Mel-200 group had greater proportion of patients with IgG myeloma (78% vs 38%) and shorter time from diagnosis to transplant (301 days vs 581 days). Results: Neutrophil engraftment was similar in the two groups. However, platelet engraftment, transfusion requirements, length of stay and number of days on antibiotics were worse in the Mel-TBI group. The complete and very good partial responses were high in both groups Mel TBI 58.6% vs Mel-200 56% (p=0.81). Median overall survival (OS) was 3.5 years and 3.8 years for Mel TBI and Mel-200 groups, respectively (p=0.75). Event-free survival (EFS) was 1.9 years and 2.3 years, respectively (p=0.88). Survival after relapse post-PBSCT was short, median 1.1 and 1.8 years, respectively. We present here the results of two groups of myeloma patients treated consecutively in a single institution. The Mel-200 patients had a higher proportion of IgG myeloma and were transplanted earlier in the phase of their disease. As expected, regimen-related toxicities were higher in the Mel-TBI group. The response rates, OS, and EFS were similar. These results are in keeping with published reports of prospective randomized studies. Mel-200 is now the standard conditioning regimen for autologous transplant for myeloma.
Generation of Novel, High Titre, Multi-Cistronic Retroviral Vectors Which Simultaneously Express Individual Proteins in Different Subcellular Locations of Hematopoietic Cells.
Authors: Milsom Michael D. , Gavin Catherine , Baldwin Rebecca , Margison Geoff , Fairbairn Leslie J. 
Published: October 2019

Abstract
As gene therapy strategies become ever more sophisticated, there is a need for vectors which efficiently deliver and express more than one gene product to target cells e.g. to enable in vivo selection; to correct multiple genetic loci; to provide a suicide mechanism for safety purposes. Employing alternate codon usage, we have synthesised a novel version of the FMDV 2A self-processing moiety which encodes the same primary amino-acid sequence as the wild type protein (and which possesses equivalent cleavage activity to the wild type protein). By including this synthetic FMDV 2A sequence in retroviral vectors which also contain the wild type sequence, we are able to facilitate the efficient co-translational separation of 3 different proteins encoded by a single transcript. This vector configuration also permits the inclusion of an IRES sequence and thus expression of a fourth protein. Using this technology we have created two tetracistronic retroviral vectors which express eGFP; O6-methylguanine DNA-methyltransferase and truncated human nerve growth factor receptor courtesy of 2A mediated cleavage, and a mitochondrially targeted dsRED via an IRES. Stable amphotropic producer lines containing these vectors generated supernatant which contained a high titre of retroviral particles (>106 IU/ml) which was sufficient for the transduction of K562 human erythroleukemic cells. Analysis of transduced cells confirmed that all four proteins were expressed individually and segragated to their correct subcellular locations. Furthermore, limiting dilution assay revealed that proteins expressed courtesy of the 2A sequences were still generated at high levels, even when cells were infected with a low MOI of virus. We propose that this technology will allow the creation of more sophisticated vectors for use in gene therapy of hematopoietic and other cells.
VEGF Specific siRNAs Act Synergistically with Bortezomib and Steroids in Inhibiting VEGF Gene Expression, Proliferation and Induction of Apoptosis in Multiple Myeloma Cells.
Authors: Koldehoff Michael , Steckel Nina K. , Trenschel Rudolf , Beelen Dietrich W. , Elmaagacli Ahmet H. 
Published: October 2019

Abstract
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of malignant plasma cells within the bone marrow (BM). Vascular endothelial growth factor (VEGF), a glycoprotein produced by normal and neoplastic cells is an important regulator of physiological and pathological angiogenesis. MM cells secrete VEGF, which promotes production of cytokines in bone marrow stromal cells, as well as migration and proliferation of the tumor cells. Inhibition of VEGF activity or disabling the function of its receptors has been shown to inhibit both tumor growth and spread of metastases in a variety of animal tumor models. RNA interference (RNAi) is rapidly being established as a post-transcriptional gene silencing method and holds promise to specifically inhibit gene expression in mammals. Another novel class of antitumor agents is based on the inhibition of the ubiquitin-proteosomal system which represents the major nonlysosomal pathway through which intracellular proteins are degraded in eukaryotic cells. Bortezomib, a reversible proteosome inhibitor, shows remarkable anticancer activity in various malignant cell types, including MM cells that are resistant to conventional therapies. We studied the effect of transfection with small interfering RNA (siRNA) targeting VEGF in MM cells in terms of proliferation, induction of apoptosis, and cell differentiation. Further, we evaluated if the effects of post-transcriptional gene silencing by VEGF specific siRNA can be augmented by bortezomib and/or steroids in the cell line OPM-2. A mean reduction of VEGF gene expression to 38% as determined by real-time PCR was observed with 0.8 ug VEGF siRNA in OPM-2 cells compared to controls (controls were set up to 100%). Simultaneous administration of bortezomib and siRNA was able to reduce VEGF gene expression down to 23% compared to VEGF siRNA alone demonstrating a synergistic effect of combined bortezomib and siRNA treatment. We found a 2.5-fold increase in induced apoptosis in OPM-2 cells subsequent to VEGF siRNA administration but we saw no additional stimulation of apoptosis after combination of VEGF siRNA with bortezomib and/or steroids. Proliferation in OPM-2 cells was strongly inhibited (about 91%) following combination treatment as opposed to only 62% after administration of VEGF siRNA alone. The transfection of VEGF siRNA in OPM-2 cells had no influence on the expression levels of differentiation markers such as CD38, CD138, CD19, CD34, CD45, and CD7AAD. Our findings suggest that synergistic effects of VEGF siRNA with bortezomib and dexamethason may offer new therapeutic options in the treatment of MM.
Prospective Clinical and Epidemiological Evaluation of rHuEPO in the Routine Care of a Network of Hematological Centers.
Authors: Barbui Tiziano , Romero Marilena , Delaini Federica , Sasso Elisa , Tognoni Gianni , Cazzola Mario 
Published: October 2019

Abstract
The expected effects of rHuEPO treatments on the quality of life of patients exposed to chemotherapeutic regimens have favored its widespread clinical utilization, even in the absence of a solid consensus on the criteria for assuring an optimal cost-effectiveness and safety profile.
A prospective multicenter outcomes-oriented observational protocol adopted by a network of 29 hematological centers has explored specifically the relationship between the yield of rHuEPO, therapy and the levels of endogenous EPO in a cohort of 478 consecutively diagnosed patients (55% males), with NHL (43%), CLL (16%), MM (41%), in first (287, 60%) and successive (191, 40%) chemotherapy line. Over the 12 months follow-up, 4/252 and 32/226 patients with Hb > 11 g/dl and < 11 g/dl died; up to 20% of those with inadequate EPO levels did not receive rHuEPO, while 16/35 (46%) of those with adequate EPO levels were prescribed rHuEPO. At a multivariate analysis, only patients with baseline Hb levels between 10 and 11 g/dl and in first line chemotherapy regimen, but not those with levels < 10 g/dl or in > 1st. line therapy benefited from rHuEPO.
Conclusions: While providing an informative epidemiological profile of the patients exposed to rHu EPO during chemotherapy and of the care they receive in the routine practice of specialized centers, the study documents some of the areas of uncertain practice, and confirms the need of prospective, controlled trials in the specific value of rHu EPO in well-characterized subpopulations on chemotherapy for hematological malignancies.
Recommandations of the Societe Francaise des Cancers de l’Enfant (SFCE) for the Management of Tumors Lysis Syndrom (TLS) : A Validation Survey.
Authors: Bertrand Y. , Auvrignon A. , Nelken B. , Mialou V. , Mechinaud F. , Brethon B. , Patte C. , Plantaz D. , Urbieta M. , Baruchel A. , Leverger G. 
Published: October 2019

Abstract
TLS is a frequent metabolic complication of hematologic malignant diseases which can generate important renal impairment. As described in previous studies (Goldman S.C. et al, Blood2001;97, 2998–3003 and Pui C.H. et al., J.Clin.Oncol.2001;19, 697–704), there are High Risk (HR) patients (pts) of TLS. Rasburicase a recombinant urate oxidase enzyme transforms uric acid into the highly soluble compound allantoin which is then excreted by the kidneys. Rasburicase is highly effective in prevention and treatment of TLS. Based on these studies, the SFCE made the following recommandations for the management of TLS in children. HR pts are defined as : B cell Acute Lymphoblastic Leukemia (ALL), ALL or Acute Myeloblastic Leukemia (AML) with initial leukocyte count of at least 50x109/L, Stage III and IV T or B Non Hodgkin Lymphoma (NHL), any leukemia or NHL with a plasma uric acid concentration of at least 300 mmoles/L if <10 years old or 350 mmoles/L if >10 years old, serum creatinine or lactate deshydrogenase concentration (LDH) exciding twice the upper limit of normal (N), hyperphosphatemia ≥2mmoles/L. These pts are treated by hyperhydratation (3L/m2) ±alkaline and Rasburicase 0,20 mg/kg/d x 5days. Rasburicase is carried on if serum creatinine > 1,5N or phosphatemia >3mmoles/L or plasma uric acid concentration ≥200mmoles/L and until normalization. Low Risk (LR) pts are defined as pts not HR. They are treated by hyperhydratation (3L/m2) and Rasburicase 0,20 mg/kg/d for one day only. Rasburicase is carried on during 4 days or more on the same biological basis as HR pts. In order to check the validity of those guidelines, we are conducting a survey looking at the evolution of the pts managed according to the SFCE recommandations.150 pts are planned for a 6 months study. On July 30th, 39 pts are registred : 25 ALL, 6 AML, 8 NHL (3 Burkitt). At that time there is no SLT complication. Results will be presented at the 2004 ASH Meeting.
Time and Cost Savings with Bio-Set® Device in Reconstituting FVIII Concentrate.
Authors: Brewster Jessica , Mannix Sally , Butler Regina , Lloyd Andrew , Rentz Anne M. , Larson Peter J. 
Published: October 2019

Abstract
Introduction: Bio-Set® (Biodome, Issoire France) is a new needleless device developed for the reconstitution of a factor VIII concentrate, Kogenate® FS (Bayer HealthCare, Elkhart IN).
Objectives: Quantitate time required to prepare FVIII concentrate for infusion and estimate the cost of medical waste produced using 3 reconstitution methods.
Methods: 161 subjects (35 patients; 67 caregivers; and 59 nurses) were recruited from the US and Canada following an IRB-approved protocol. Reconstitution methods were Bio-Set®, the conventional 2 vial transfer needle reconstitution method, and 2 vial Baxject method (Baxter Healthcare, Westlake Village CA). Video and interviewer demonstrations were conducted, then participants practiced each reconstitution method once before performing a timed round. Diluent volume for the conventional reconstitution method and Baxject were controlled at 5 mL. After each timed round, participants separated reconstitution refuse into either medical waste or regular trash. The weights of component pieces were added and a cost for disposal of the medical waste was determined.
Results: Participants completed preparation of the infusion with Bio-Set® in the shortest amount of time compared to the conventional method and Baxject (both p<0.0001). Results were similar across the 3 participant groups. The average weight of medical waste was lowest for Bio-Set® and highest for Baxject. The resulting disposal cost was significantly lower for Bio-Set® (p<0.0001).
Conclusions: The results of the time study showed a reduction of 33% in infusion preparation time with the Bio-Set® when compared to the conventional method and 29% when compared to the Baxject. The cost of disposal of medical waste should be reduced with the use of the Bio-Set®.
An Evaluation of the Effectiveness of Darbepoetin alfa 300 mcg Every 3 Weeks (Q3W) on Clinical Outcomesin Cancer Patients with Chemotherapy-Induced Anemia.
Authors: Boccia Ralph Vincent , Liu Delong , Silberstein Peter , Tchekmedyian Simon , Tomita Dianne , Rossi Greg , Otterson Greg 
Published: October 2019

Abstract
Darbepoetin alfa (Aranesp®) administered at 300 mcg Q3W appears to be an effective dose in patients with hemoglobin (Hb) 10–12 g/dL to maintain Hb, and in patients with Hb 8–10 g/dL to elevate Hb to within the National Comprehensive Cancer Network (NCCN)-recommended target range of 11–12 g/dL. The objective of this multicenter, open-label study of cancer patients with chemotherapy-induced anemia was to evaluate the effectiveness of darbepoetin alfa 300 mcg Q3W, administered over a 16 week treatment period, in achieving and maintaining the therapeutic objectives of anemia treatment consistent with NCCN guidelines. This objective was assessed by determining the percentage of patients who achieved a post baseline target Hb level ≥11.0 g/dL in the absence of a transfusion within the previous 28 days, and the percentage of patients maintaining an average Hb within the NCCN target range. Secondary hematologic endpoints included the incidence of transfusion and the proportion of patients achieving a hematopoietic response (increase in Hb ≥2 g/dL from baseline or achieving a Hb ≥12 g/dL). Patient-reported outcomes were assessed using the FACT-Fatigue subscale with four additional questions relating to fatigue, energy, activity, and overall health. The relationship between clinical endpoints and the ability to achieve and maintain Hb within the NCCN target range were also assessed. Anemic patients (baseline Hb levels < 11 g/dL) with nonmyeloid malignancies receiving chemotherapy were eligible for enrollment in this study. Doses could be escalated after 6 weeks (2 doses) to 500 mcg Q3W if Hb levels remained < 10 g/dL and the increase in Hb from baseline was < 1 g/dL, or, based on physician discretion if Hb levels were > 10g/dL. To date, 539 patients have been enrolled. The majority of patients were female (59%), white (82%) with a median age of 64 years. The predominant cancers in these patients were lung (24%), gastrointestinal (22%), and breast (21%). The majority of patients had stage IV disease (45%) and a Karnofsky performance status score of 80 to 90 (65%). The mean (SD) baseline Hb level was 10.1 g/dL (0.7); 32% of patients had a baseline Hb of < 10.0 g/dL [mean (SD) Hb 9.3 (0.6) g/dL] while 66% had baseline Hb levels ≥10.0 g/dL [10.6 (0.3) g/dL]; 2% of patients (n = 12) received a transfusion within 28 days of baseline Hb measurement and were excluded from analysis. Since the majority of chemotherapy regimens are delivered on a Q3W basis, the ability to administer darbepoetin alfa at a fixed dose, synchronized with the chemotherapy schedule may reduce the number of injection-centric visits. This provides important benefits for patients and their caregivers, and represents a simplification in the treatment of chemotherapy-induced anemia in oncology practice.