bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of 100-Day Survival on Outcome of Myeloablative Unrelated Bone Marrow Transplantation at an Early Stage of Leukemias.
Authors: Hiraoka Akira 
Published: October 2019

There is a growing demand for quality improvement in hematopoietic stem cell transplantation as in other fields of patient manegement. Indicators would be necessary for the quality control, which finally lead a continuoous quality improvement process. We analyzed the impact of 100-day survival on the outcome in leukemia patients receiving a myeloablative unrelated BMT at an early stage of leukemias. Data on 1,203 patients who received a myeloablative unrelated BMT at the first CR of acute leukemia or the first chronic phase of CML between 1993–2001 were retrieved from Japan Marrow Donor Program Registry’s database. There were 40 hospitals which performed more than 10 BMTs during this period. A significantly lower 100-day survival than the average of all patients (n=822) was found in six hospitals (group 1). The remaining 36 hospitals were grouped in group 2. Overall survival (OS) at 1-year was 0.56 in group 1 (n=125) and 0.75 in group 2 (n=697) (p<0.001).
Figure Figure
The 100-day survival was 0.66 (83/125) in group 1 and 0.90 (625/697) in group 2 (p<0.001). OS at 1-year for survivors over 100 days was 0.828 in group 1 and 0.832 in group 2 (p=0.9).
Figure Figure
After adjustment for age (~15, 16~39, 40~), type of leukemia (CML, ALL, ANLL), and group (1, 2) by using the Cox regression model, patients in group 1 were found to have a higher risk of death than patients in group 2 (Hazard Ratio 2.14; 95% CI 1.58–2.90). These results indicate that
among hospitals which performed more than 10 BMTs between 1993–2003, 6 hospitals showed a significantly lower 100-day survival than the average of all patients, OS at 1-year for survivors over 100 days in patients in these 6 hospitals was simillar in patients in the remainging 34 hospitals, and after adjustment of age, type of leukemia and hospital group by using Cox regression model, patients in these 6 hospitals were found to have a higher risk of death than patients in the remaining 34 hospitals.
Thus, the 100-day survival might be an indicator for the quality control in leukemia patients who receive a myeloablative unrelated BMT at an early stage of leukemias.
Optimizing Results of Unrelated Donor Hematopoietic Stem Cell Transplantion in Developing Countries: Young Age and Early Disease as Positive Factors for Survival.
Authors: Funke Vaneuza A.M. , Nunes Elenaide C. , Cezario Eliane , Ruiz Jefferson , Setubal Daniela C. , Oliveira Michel M. , Bonfim Carmem M.S. , Bitencourt Marco A. , Pettengil Claudia , Medeiros Larissa , Datamager Heliz Regina A. Neves , Neto Jose Zanis , Medeiros Carlos R. , Pasquini Ricardo 
Published: October 2019

Abstract
Introduction: Unrelated donor hematopoietic stem cell transplantation (HSCT) has been carried out in Brazil since 1995, with an increasing number of procedures among the transplant centers. Evaluating this experience is important to improve the outcomes of this therapeutic modality. The aim of this study is to assess risk factors for survival in 125 patients who underwent unrelated donor HSCT for malignant diseases.
Material and methods: 125 patients with malignant diseases who received unrelated donor HSCT between july/95 and june/2005 in a single institution in Brazil were analyzed. Kaplan-Meier curves were used to estimate overall survival, log-rank test for comparison of continuous variables and Fisher exact test for categorical variables. Cox proportional hazard model was used for analyzing risk factors for survival. Analyzed risk factors: sex, age, acute graft-versus-host-disease (a-GVHD) grades II-IV, extensive chronic (c) GVHD, diagnosis, stage of disease, source of stem cells, number of infused cells/Kg and HLA matching. Median age was 17 years (range 1–55), male (n=78) and female (n=44).
Diseases: CML (n=46), AML/MDS (n=40), ALL (n=34), other (n=5). Source of stem cells: bone marrow (n=95), umbilical cord blood (n=30). ATG or ALG containing regimens were used in 25 patients. Advanced disease was detected in 66 patients (53%) and was defined as CML in advanced phases, AML and ALL ≥ second clinical remission (CR2), relapsed or refractory.
Results: Acute GVHD II-IV was observed in 51 (41%) patients and extensive c-GVHD in 32 (26%). Main death causes: a-GVHD (9%), c-GVHD (13%), infections (41%) and relapse (27%). Estimated overall survival (OS) in 10 years was 40%, with a median survival of 189 days. Sex, diagnosis, stem cell source, type of conditioning, number of infused cells/Kg and HLA matching did not influenced survival. OS in 10 years was higher in patients with early stage disease compared to advanced diseases (55% × 20%; p=.0005) and in patients under 18 years of age compared to those ≥ 18 years-old (60% × 20%; p=.0012). The presence of extensive c-GVHD had a positive influence in OS (OR 0,1758 – 0,9092).
Conclusions:
The OS in 10 years was 40% for this group of patients. Patients in early stage disease and under 18 years of age have a higher OS in 10 years (55% and 60% respectively). Extensive c-GVHD had a positive impact in survival, probably due to graft versus leukemia effect.
Autologous Stem Cell Transplantation for Elderly Patients with Multiple Myeloma.
Authors: Qazilbash Muzaffar H. , Saliba Rima , Hosing Chitra , Mendoza Floralyn , Qureshi Suhail R. , Weber Donna M. , Wang Michael , Flosser Thuy , Couriel Daniel R. , De Lima Marcos , Kebriaei Partow , Popat Uday , Alousi Amin M. , Champlin Richard E. , Giralt Sergio A. 
Published: October 2019

Abstract
Background: Several trials have shown that autologous stem cell transplantation is superior to conventional therapy in terms of complete response (CR) rate, event-free survival (EFS) and overall survival (OS). This treatment, however, is generally limited to patients younger than 65 due to concerns about excessive toxicity and treatment-related mortality (TRM) in older patients. Previous reports have shown that age alone should not exclude patients from high-dose therapy, as long as they fulfill other eligibility criteria. In this report we analyzed the safety and efficacy of high-dose chemotherapy (HDT) and autologous transplant in patients with MM who were ≥ 70 years at the time of autotransplant.
Methods: Twenty-six patients (16 males, 10 females) with a median age of 72 (range 70–79) underwent HDT and an autograft between July 1999 and October 2005. The preparative regimen was melphalan 200 mg/m2 in 19 patients (73%), melphalan 180 mg/m2 in 6 and melphalan140 mg/m2 in 1 patient. Of the 26 patients, 12 were receiving first remission consolidation, 7 had primary refractory disease and 7 had relapsed disease. Clonal cytogenetic abnormalities were present in 5 patients (19%).
Results: Twenty-two of the 26 patients were alive after a median follow up of 15 months (range 2–63). Responses (complete + partial response) were seen in 20 patients (77%), five (19%) of which were complete responses. Median EFS and OS were 19 and 31.6 months, respectively. 100-day TRM was 0%. Median times to absolute neutrophil count of ≥0.5 × 109/l and platelets ≥20 × 109/l were 10 and 10 days, respectively. Three-year EFS and OS were 37% and 49%, respectively. A low serum albumin (<3.5 g/dl) was associated with a shorter EFS (p=0.02), and patients with relapsed disease at transplant had a shorter OS (p=0.002). ISS stage, b2 microglobulin level, lactic dehydrogenase (LDH) level, abnormal cytogenetics, CCI or HCT-CI at the time of transplant did not emerge as significant predictors of PFS or OS in this group of patients.
Conclusions: HDT and autologous transplant is safe and feasible in selected patients ≥70 years of age. The outcome is comparable to younger patients undergoing an autograft, and older patients receiving conventional therapy.
Autologous Stem Cell Transplant Followed by Low Dose Rituxan Maintenance in CR1 Is Effective for the Treatment of Mantle Cell Lymphoma.
Authors: Lim Seah H. , Esler William V. , Beggs David , Burris Colleen , Zhang Yana , Townsend Mary 
Published: October 2019

Abstract
Conventional chemotherapy is non-curative for mantle cell lymphoma (MCL). Although the addition of Rituxan has improved the outcome of these patients, many patients still relapsed and died of their disease. High dose chemotherapy followed by autologous stem cell transplant (ASCT) has been investigated but produced conflicting results, ranging from no demonstrable benefit to a 2-year event-free survival (EFS) of 77%. A recent randomized study compared ASCT with interferon-a maintenance and showed benefits in both the EFS and overall survival for patients in the ASCT study arm. The conflicting results are probably related to the use of different chemotherapeutic agents as conditioning regimens for the transplant and also to different post-transplant therapy.
In this study, we have chosen to induce patients with advanced MCL with R-CHOP and consolidate these patients with high dose single agent melphalan, a cytotoxic that has not been previously tested as a single agent in MCL. Since most patients relapsed within the first two years after transplant, low dose maintenance Rituxan therapy is given three-monthly during the first 2 years after ASCT. Following consent from the patients, 8 consecutive patients with advanced Stage III or IV MCL were treated. There were 5 male and 3 female, with a median age of 642 years (range 46–72 years). One patient had Stage III and the other 7 Stage IV diseases. All eight patients received remission + 2 courses of R-CHOP as induction chemotherapy. Autologous stem cells were harvested upon recovery from the last course of R-CHOP and ASCT carried out within 6 weeks from the last course of R-CHOP. High dose intravenous melphalan (200 mg/m2) was administered followed, 24 hours afterward, by the infusion of a minimum of 2 × 106/kg of CD34+ autologous stem cells. Rituxan maintenance therapy was initiated at a dose of 375 mg/m2 given as a single infusion once every three months starting Day +100.
As of August 2006, with a median follow-up of 45.5 months from diagnosis (range 10–57 months) and 39 months from ASCT (range 4–52 months), seven patients are alive lymphoma-free, as defined by clinical and PET-CT examination. One patient died in CR of a myocardial infarction. Adverse effects were as expected from the high dose melphalan, except that delayed immunoglobulin reconstitution, as reported previously, was observed in all eight patients. Four of these hypogammaglobulinemic patients had recurrent infections (three with recurrent respiratory tract infection and one with a chronic diarrhea that was Vancomycin sensitive) and two required monthly intravenous immunoglobulin replacement. The result presented here is, therefore, extremely encouraging for a group of patients who normally have a very poor clinical outcome and warrants confirmation in larger multicenter study.
Role of High-Dose Chemotherapy with Autologous Haematopoetic Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Disease.
Authors: Kumar Ambuj , Djulbegovic Benjamin , Soares Heloisa P. 
Published: October 2019

Abstract
Background: Hodgkin disease (HD) is a potentially curable lymphoma with overall survival exceeding 60% at 10 years. However, patients with relapsed Hodgkin’s disease have a dismal prognosis when treated with conventional salvage chemotherapy. The primary objective of our systematic review/meta-analysis was to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with relapsed Hodgkin’s disease which has not been done before.
Methods: Data search of published studies included Medline (1966–2006), Cochrane library and hand search of references. Studies were included if they were randomized controlled trials of HSCT versus conventional chemotherapy only. Data were extracted on benefits as well as harms (overall survival, event-free survival, and treatment related mortality). All data extraction was done in duplicate independently.
Results: Out of 47 identified studies only 2 met the inclusion criteria of the current systematic review. Overall survival was similar for HSCT and conventional chemotherapy arms (see figure 1) with a pooled hazard ratio (HR) of 0.69 (95%CI 0.40, 1.18, p=0.2). However, the event-free survival was better in the HSCT arm than the conventional chemotherapy alone group (HR = 0.59, 95%CI 0.41, 0.85, p=0.005). Treatment related mortality was similar in both groups. (HR = 0.40, 95%CI 0.11, 1.44, p=0.2).
Conclusion: Results from our meta-analysis indicate that treatment with HSCT compared with conventional chemotherapy only improves event free survival without excessive toxicity. However, overall survival was not affected by the HSCT therapy. In summary patients with relapsed Hodgkin’s disease should be offered HSCT therapy.
Role of transplant in relapsed or resistant hodgkin’s disease Role of transplant in relapsed or resistant hodgkin’s disease
Factor Xa Control of the Extrinsic Pathway: A Different View of the Regulation of Coagulation.
Authors: Hathcock James J. , Rusinova Elena , Nemerson Yale 
Published: October 2019

Abstract
The activation of factor X by Tissue Factor(TF):VIIa on a membrane surface is one of the principal events in the initiation of coagulation. We have previously shown and presently confirm that reactions initiated by TF:VIIa do not typically result in the complete activation of substrate, but rather some intermediate level of fX activation. Excess phospholipid has complex effects on the TF:VIIa reaction, resulting in either inhibition, due to substrate depletion, or acceleration, by virtue of binding fXa. This complexity results in unavoidable ambiguities in interpretation of all previous reports. To tease apart these complexities, we have used benzamidine-sepharose that only binds fXa and not fX. We now show that the reaction product, fXa, can impede, and in fact, completely inhibit TF:VIIa activity. We monitored progress curves of fX activation by TF:VIIa in the presence and absence of benzamidine beads, which specifically partition the reaction product away from the TF:VIIa complexes. In the presence of these benzamidine beads, the activation rate of fX increased by 60% confirming that removal of fXa enhances tissue factor activity. Moreover, binding studies of fXa to TF-phospholipid surfaces indicate that the surface occupancy by fXa regulates TF:VIIa activity. Surface occupancy was evaluated by Total Internal Reflectance (on macroscopic lipid bilayers) and Fluorescence Resonance Energy Transfer (phospholipid vesicles). Our measurements of the off-rate of fXa (0.06–0.08 /s) are similar to some literature values, but differ by up to 500-fold from others. Stochastic simulations of TF:VIIa kinetics on phospholipid surfaces confirm that product leaving rates strongly regulate the observed experimental kinetics. Our approach indicates that current models of coagulation need to be altered to accommodate product surface occupancy. Indeed, if fXa occupancy is ignored, as is generally the case, the models simply cannot reflect reality.
Target Marker Gene Expressions and the Possibility of Molecular Therapy for Children’s Brain Tumors.
Authors: Tsuruta Toshihisa , Kanno Hitoshi , Aihara Yasuo , Hamada Takako , Sakauchi Masako , Osawa Makiko , Wada Emiko , Kubo Osami , Hori Tomokatsu , Fujii Hisaichi 
Published: October 2019

Abstract
ErbB2, c-Myc and p53 gene expressions are widely reported for the poor prognostic markers for medulloblastoma (MB) patients. Recently, Wnt pathway and Sonic Hedgehog (SHH) pathways are known to related to the oncogenesis of MB cells, and the PDGF receptor gene and some adhesion molecule gene expressions are also known to the markers of the dissemination or the metastasis of MB cells. For adult malignant brain tumors, the molecular targeted therapy of the antibody (trastuzumab, cetuximab), the tyrosine kinase inhibitor (imatinib, gefinitib) or other signal transduction inhibitor (cyclopamin) are clinically researched. We examined several important marker gene expressions of the molecular therapy in various children’s brain tumors and searched the possible molecular targeted therapy.
[Materials and methods] Fifteen children’s brain tumor (five MB, seven glioma, three ependymoma) and four adult brain tumor (two glioma, two glioblastoma) were examind. The three MB cases were primary metaststic ones. The mRNA expressions of the marker genes (ErbB2, PDGF receptor, PCNA, SPARC, β-catenin, SUFU, c-Myc, p53, TrkC and so on) were examined by quantity polymerase chain (qPCR) reaction with fresh frozen tumor cells. For the normal control, we used the normal cerebellum total RNA samples of the Becton, Dikinson and Company. CYBR green coloring system was used for the qPCR and their primers were designed in the region between two exons. GAPDH gene expression was also examined as an internal control and all of the gene expression were normalized by GAPDH expression.
[Results] ErbB2 gene expression in MB cells were various, but their expression were similar to clinical futures, such as, the higher expressed cases had some high risk factors. In glioma cells, ErbB2 gene expression were almost equal by lower levels. PDGF receptor gene expression were more than five to ten times elevated in all of the glioma cells, even if they were low grade malignancy glioma, and were higher than that in MB cells. PCNA was specially elevated in primary metastatic MB cells.
[Conclusion] Our data shows that the molecular characteristics of the children’s brain tumors were thought to be different by cases, even if they had same histopathological characters. Some special gene tageting therapy, such as anti-ErbB2, PDGFR and/or PCNA therapy can be used for the various children’s brain tumors which are resistant for conventional therapies and are cured by adequate molecular therapy.
Gene Therapy for Beta-Thalassemia: Preclinical Studies on Human Cells.
Authors: Ferrari Giuliana , Roselli Emanuela , Tiboni Francesca , Biral Erica , Marktel Sarah , Antoniou Michael , Andreani Marco , Lucarelli Guido , Cesari Rossano , Miccio Annarita 
Published: October 2019

Abstract
Gene therapy for beta-thalassemia is based on the transplantation of genetically-modified autologous hematopoietic stem cells (HSC) into patients affected by the severe form of disease. The genetic treatment of the hemoglobinopathies poses the general challenge of efficient level of gene transfer into HSC and high and persistent transgene expression, in the differentiated progeny of a genetically modified stem cell. The validation of a gene therapy approach to thalassemia requires to obtain results of gene correction in a broad number of patients’ cells, since different molecular defects in the beta-globin gene lead to the clinical phenotype. The heterogeneity in the molecular defects and in the proportion of alpha and non-alpha (beta, gamma and delta) chains will represent a key element to set a threshold in the amount of vector-derived beta-chain required to correct a thalassemic phenotype. Additionally, the impact of some biological parameters, such as the degree of BM erythroid hyperplasia, the BM subpopulations proportion and the apoptotic index, on the successful correction of thalassemic phenotype needs to be studied in the perspective of clinical translation. In order to address these issues, we collected samples from BM aspirates and isolated CD34+ cells from 25 beta+ and beta0 thalassemic patients, characterized by different genotypes and biochemical profiles of globin chains synthesis. A novel, erythroid specific LV expressing human beta-globin from a minimal promoter enhanced by only 2 LCR elements (HS2 and HS3) was used to transduce BM derived CD34+ cells at high efficiency (>80%). The efficacy of the beta-globin LV in correcting the human thalassemic phenotype was tested in an in vitro model of erythropoiesis and in the human-mouse hematological chimera. Upon transduction, normal level of HbA expression was achieved in erythroblastic cultures and BFU-E, associated with a progression towards erythroid maturation, which was impaired in mock-transduced thalassemic cells. Molecular analysis showed proviral integrity, with no detectable rearrangements and an average proviral copy number of 2.4. Analysis of specific globin chains proportion and contribution to phenotype correction in the context of different genotypes is under evaluation.
Clinical Significance of Reticulocyte Hemoglobin as a Diagnostic Tool for Evaluation of Anemia in Veterans.
Authors: Nair Bijay , Spencer Horace J. , Raval Girindra G. , Mehta Paulette 
Published: October 2019

Abstract
Reticulocyte hemoglobin content (CHr), is a reliable marker of iron function, rather than iron stores alone, especially in patients with renal failure. Whether it is as effective in patients with hematologic and oncologic disease is not known. We therefore evaluated the usefulness of CHr for diagnosis of different types of anemia among the Veterans at the CAVHS (Central Arkansas Veteran Healthcare System), Little Rock. We evaluated all patients with anemia seen in the Hematology/Oncology clinic at CAVHS from 7/1/2004 through 6/30/2006. We obtained demographics of patients and laboratory data including CBC, reticulocyte count, CHr, serum iron, total iron binding capacity (TIBC), iron saturation, ferritin, vitamin b12 and folate from the CPRS electronic database. Using STATA program, we analyzed the relation between CHr, RBC indices and other iron storage parameters. A total of 183 patients were evaluated. Patients had mean age 69, ranging from 35 to 98 years. The majority were men with only 9 women. Patients were whites (75%), African Americans (17%), or others (7%). Mean CHr was 32 pg with range from 18.7 to 50.4 pg (normal value 24 to 36 pg). High CHr (>36 pg) was present in 24 patients (13.1 %). High CHr was associated with high MCV in all cases and included patients with vitamin b12 deficiency, myelodysplasia, myelofibrosis, large granular lymphocyte leukemia, chronic lymphocytic leukemia, autoimmune hemolytic anemia, HIV infection on HART as well as those who had received total body irradiation or were taking methotrexate, or azathioprine. Low CHr (<24pg) was present in 8 patients. All of them had low MCV and had iron deficiency anemia, including one with ferritin over 1000ug/ml, presumably high as an acute phase reactant since iron saturation was only 6%. This patient had active head and neck cancer and had received chemotherapy and radiotherapy. CHr did not correlate with other parameters of iron such as ferritin (r=0.14), iron saturation (r=0.57) or TIBC (r= −0.16) in the pooled analysis of all anemias. CHr did correlate well with RBC indices MCV (r=0.86) and MCH (r=0.89) but not so well with MCHC (r= 0.62).
In summary, Reticulocyte hemoglobin content is a good marker of iron function and may be superior to ferritin since it does not change with acute conditions. However it correlates well with MCV and MCH, and therefore does not appear to provide significant independent diagnostic advantage over MCV. Since MCV is readily available and is inexpensive, CHr offers relative little advantage for routine evaluation of anemia.