bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Clinical Research of Umbilical Cord Blood Transplantation for Children with Leukemia or Whom with Beta-Thalassemia.
Authors: Fang Jianpei , Huang Shaoling , Zhou Dunhua 
Published: October 2019

Abstract
Objective To evaluate the clinical efficacy and complications of related (RD) umbilical cord blood transplantation (UCBT) or unrelated (UD) UCBT for children with leukemia or whom with b-thalassemia (TM).
Methods Ten patients with TM received RD-UCBT (group 1), while another 10 patients with TM had UD-UCBT (group 2).13 patients with leukemia (4 high risk ALL and 9 AML) were transplanted from UD-UCB (group3). Of 7 were HLA-identical, a patient was a loci-mismatched and two of them were half matched in group 1. Meanwhile, in the group2, three of ten patients were HLA matched, six was a loci-mismatched and one received double unites of UD-UCB that was from HLA matched to a loci-mismatched. Furthermore, ten of 13 patients were one loci-mismatched in group 3. Two were two loci-mismatched and one received double unites of UD-UCB from HLA matched to a loci-mismatched in the group. The conditioning regimen was consisted of busulfan (Bu) 14–20 mg /kg, cyclophosphages(Cy) 120–200 mg /kg and horse antithymocyte globulin (ATG)90 mg /kg or rabbit ATG 25 mg /kg for all TM patients. Of them, 6 also received melphalan (Melph) 90 mg /m2. Four patients had fludarabine (Flu) 150 mg /m2. Three combined Flu with thiotepa (TT) 6 mg /kg. Five used Flu, TT and TBI together. In the group of patients with leukemia (group 3), the regimen was divided into two branches: (1) Non-TBI regimen: the regimen mainly focused on 10 patients with leukemia in the CR phase except a patient was too young although him in the NR phase, which was consisted of Bu, Cy, ATG and Flu. A patient added high dose Ara-C. One had IDA, and 3 Melph. (2). Accompanying with TBI regimen. Only had two patients who were in the phase of NR used this regimen. The dose of TBI was 7.5 Gy and 6.5 Gy respectively. The patients received the nucleated cells 7.5 (3.4–19.4)’107/kg, CD34 cell 4.5 (0.6–11.7) ’105/kg, CFU-GM 1.1 (0.2–23) ’105/kg in three groups.
Result: The engraftment occurred 7 in 10 at the group 1. One patient developed acute GVHD grade III. Two patients rejected 2 months post RD-UCBT. The following up was from 34–69 months in the group and 4 cases remained in the EFS. However, only 3 out of 10 were engraftment in the group 2. The others all were antologous reconstitution in the failure patients. One developed acute GVHD grade II in the group 2. The following up was from 3 months to 43 months in the group. Two cases kept EFS but one died of IP at the 6 months post transplantation. 11 out of 13 patients engrafted in the group 3. Nine patients were EFS post transplantation and the time of following up was from 4 to 37 months in the group. One developed severe acute GVHD and 3 had extensive chronic GVHD.
dSLIM Immunomodulators Induce Anti-Tumor Responses Both In Vitro and In Vivo.
Authors: Schmidt Manuel , de Cristobal Javier , Sander Astrid , Brzezicha Bernadette , Koenig-Merediz Sven A. , Wittig Burghardt 
Published: October 2019

Abstract
Cytosine-guanine (CpG) motifs containing oligonucleotides (ODN) are commonly used for immunomodulatory purpose in cancer therapy and for the treatment of allergic diseases since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response with secretion of IL-12 and IFN-γ, In addition their broad potential includes activation of B-cell proliferation, monocyte stimulation and secretion of IgM and IL-6, and stimulation of plasmacytoid DC to produce IFN-α/-β and thus γδT-cells and NK-cells to express CD69 and secrete IFN-γ. Usually phosphorothioate (PS) modifications are to enhance the stability, but these are leading to several side-effects, like severe organ enlargements, morphological changes and immunosuppression in mice. We designed immunomodulatory molecules based on short covalently-closed dumbbell-like structures (dSLIM) to stabilize the DNA without the otherwise necessary PS-modification. To evaluate the anti-tumor effect of the dSLIM molecules we developed an in vitro anti-tumor assay. This assay uses supernatant from dSLIM-activated human PBMCs for incubation with tumor cells in vitro. We observed increased apoptosis and necrosis by the HT-29 tumor cell line after incubation with supernatant from dSLIM-treated PBMC which was significantly higher than the effect of supernatant from non-treated PBMC. In addition, supernatant from dSLIM-treated PBMC increased the expression of HLA-ABC on the tumor cells, a pre-requisite for tumor cell recognition by the immune system. These effects were confirmed with human HEK293 and murine Renca cell lines. Analyzing the effect with neutralizing antibodies to various apoptosis-related cytokines, we observed a crucial role of IFN-γ but not IFN-α or TNFα. To investigate the anti-tumor effects of dSLIM in vivo, we employed a SKH1 murine model which is prone to spontaneous development of papillomas. Using chemicals for initiation and weekly promotion of de novo papilloma development we compared groups of weekly s.c. or i.p. dSLIM injections, respectively, with the PBS control group. The number of papilloma developing mice was significantly lower in the dSLIM groups and the total number of papillomas on all mice was reduced by approximately 50%. In conclusion, we showed that dSLIM immunomodulators exhibit potent anti-tumor effects in vitro and in vivo.
A National Survey of Treatment Practices for Elderly Cancer Patients in India.
Authors: Parikh Purvish M. , Arora Brijesh , Vora Amish , Nair Reena , Gupta Sudip , Sastry P.S.R.K. 
Published: October 2019

Abstract
Background: Elderly cancer patients are underrepresented in cancer services utilization and clinical research in India. National data on providers’ knowledge, attitude and practices with regard to elderly cancer patients is sparse and is urgently required to address needs of this vulnerable and growing population.
Methods: A self administered questionnaire was mailed to nationally representative sample of practicing oncologists all over India. 74 Oncologists (Medical Oncologists-58%; Radiation Oncologists-25%; Surgical Oncologists-12%; allied fields-6%) responded out of > 250 mailed Questionnaires (response rate-29%).
Results: Majority (52%) of respondents considered patients with chronological age of >60 years as elderly. Although 75%(median) of elderly patients receive some therapy, only 50% of early stage-potentially curable patients and a similar percentage of advanced stage-potentially incurable patients receive curative and palliative therapies respectively. Also, half of treated patients require modification in their treatment approach and only two-third of treated patients complete therapy. The existent barriers to treatment included poor performance status (51%), advanced stage (18%), co-morbidities (14%) and financial constraints (8%). Only 50% Oncologists always discussed and 31% always enrolled elderly patients in clinical trials. Inadequacies with respect to care and evidence based recommendations for elderly patients as compared to young patients were felt by 47% and 92% of respondents respectively. The need of separate trials for elderly and a separate discipline of Geriatric Oncology was voiced by 92% and 87% of participants respectively. Major differences in treatment practice between Hemato-oncologists and non Hemato-oncologists are highlighted in table-1.
Conclusions: Treatment practices and clinical trial accrual of elderly cancer patients in India is far from optimal. Formation of a National Geriatric Oncology society with a focus on research and treatment in this vulnerable group may enhance the understanding and clinical care of this growing population.
Table-1 : Differences in the treatment practice between Hemato-oncologists and non Hemato-oncologists Treatment Practice Hemato-oncologists(%) Non Hemato-oncologists(%) *Patients given therapy as a percentage of those eligible Age cut-off for elderly ≥60 years 59 39 Palliative therapy * 60 30 Curative therapy * 50 75 Discuss trials with patients 42 64 Enroll patients in trials 36 21 Felt inadequacy in care 52 39 Felt inadequacy in evidence based recommendations 96 85 Felt need for seperate trials 96 85
Evidence for a Novel Blood Lineage Commitment Pathway from Lympho-Myeloid Hematopoietic Stem Cells.
Authors: Jacobsen Sten Eirik W. , Mansson Robert , Hultquist Anne , Sigvardsson Mikael , Buza-Vidas Natalija , Thoren Lina , Liuba Karina , Luc Sidinh , Yang Liping 
Published: October 2019

Abstract
We recently identified a novel Lin−Sca-1+c-kithiCD34+Flt3hi (LSKCD34+Flt3hi) lymphoid-primed multipotent progenitor (LMPP) in adult mouse bone marrow which, although possessing a combined lymphoid (B and T cell) and myeloid (granulocyte-monocyte; GM) differentiation potential, have little or no ability to adopt erythroid (E) and megakaryocyte (MK) lineage fates (Adolfsson et al, Cell121:295, 2005). The identification of this lineage restricted lymphomyeloid progenitor implicates the existence of alternative roadmaps for lineage commitment of pluripotent hematopoietic stem cells (HSCs), distinct from the classical model suggesting that the first HSC commitment step results in a strict separation into common lymphoid and myeloid progenitors. Herein we provide further, genetic evidence for such a model. Affymetrix global gene profiling, quantitative PCR, and multiplex single cell PCR analysis of LSKCD34−Flt3− long-term (LT)-HSCs, LSKCD34+Flt3− short-term (ST)-HSCs and LSKCD34+Flt3hi LMPPs, demonstrate that LMPPs in contrast to LT-HSCs and ST-HSCs down-regulate or turn off a number of genes critically involved in MkE lineage development, including GATA-1 and the receptors for erythropoietin and thrombopoietin. In contrast, a number of genes specific for early lymphoid development, including Rag-1, sterile Ig and IL-7 receptor are upregulated in LMPPs but absent in LT-HSCs and ST-HSCs. Importantly, within the LMPP, these lymphoid genes are typically co-expressed with a number of GM associated genes such as G-CSF receptor and MPO, but virtually never co-expressed with MkE associated genes. Investigating fetal liver day 14.5 we also provide evidence for existence of the LSKCD34+Flt3hi LMPPs at this early stage of development, and using a single cell clonal assay promoting combined B, T and myeloid lineage development, we demonstrate that a large fraction of fetal LMPPs lacking MkE potential possess a combined GM, B and T cell potential. Thus, evaluation at the single cell level of combined lineage potentials and multilineage gene expression provide compelling evidence for lymphoid-priming within the HSC compartment being preceeded by a loss of MkE potential, but occurring prior to loss of GM potential.
Self-Managed Long-Term Low-Molecular-Weight Heparin Compared with Usual-Care Anticoagulation for Patients with Proximal Venous Thrombosis: Harm Associated with Bleeding!.
Authors: Hull Russell D. , Pineo Graham F. , Brant Rollin F. ,   for the LITE Trial Investigators
Published: October 2019

Abstract
Context: A substantial clinical need exists for an alternate to vitamin-K-antagonists for treating deep-vein thrombosis in many patients. Long-term low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and may be associated with less harm due to bleeding.
Objective: Considerable evidence suggests that reporting of harms-related data* from randomized clinical trials needs improvement. In accordance with CONSORT* we present a harm analysis regarding hemorrhagic complications.
Design: Randomized clinical trial using objective outcome measures.
Setting: 30 centres across Canada.
Participants: Acute symptomatic proximal-vein thrombosis patients.
Intervention: Therapeutic tinzaparin subcutaneously once-daily, or usual-care intravenous unfractionated heparin/vitamin-K-antagonists for 3 months.
Main Outcome Measures: Benefit was assessed by assessing the frequency of symptomatic objectively documented recurrent venous thromboembolism and harm by objectively documented hemorrhagic complications.
Results: A broad-spectrum of patients was randomized. Of 737 patients, 18 of 369 receiving tinzaparin (4.9 percent) suffered recurrent venous thromboembolism at three months compared with 21 of 368 (5.7 percent) receiving usual-care; (absolute difference, −0.9 percent, 95 percent confidence interval −4.1 to 2.4). Hemorrhagic complications occurred less frequently in the low-molecular-weight heparin group; 48 of 369 patients, (13.0 percent) versus usual-care 73 of 368, (19.8 percent), (absolute difference −6.8 percent; p=0.011; risk ratio = 0.66). The prevalence of major bleeding according to the duration of study treatment favored low-molecular-weight heparin therapy. Major bleeding persisted throughout study treatment for patients in the usual-care group receiving warfarin but ceased early by day 23 in the low-molecular-weight heparin group (p=0.034). Twenty-five patients (6.8 percent) in the low-molecular-weight heparin group and 24 patients (6.5 percent) receiving usual-care died (absolute difference 0.3 percent, 95 percent confidence interval −3.4 to 3.9).
Conclusion: Our findings are clinically relevant and important, offering the clinician an alternate therapy to vitamin-K-antagonist therapy which does not require anticoagulant monitoring in a wide range of patients with proximal venous thrombosis. Self-management with once-daily subcutaneous tinzaparin was at least as effective as usual-care and vitamin-K-antagonist therapy and offers a safety advantage with less harm due to bleeding.
Intensive Chemotherapy (LMB-86 Regimen) for AIDS-Related Burkitt’s Lymphoma/Leukemia.
Authors: Galicier Lionel , Fieschi Claire , Gerard Laurence , Chevrey Sylvie , Boulanger Emmanuelle , Daniel Marie-Therese , Meignin Veronique , Oksenhendler Eric 
Published: October 2019

Abstract
Early studies report extremely poor outcome in AIDS-related Burkitt’s lymphoma treated with standard dose chemotherapy. This poor prognosis is not improved by Highly Active Antiretroviral Therapy (HAART). 53 patients with HIV infection and stage IV Burkitt lymphoma/leukemia (BL) participated a unicentric and prospective clinical trial to evaluate the safety and efficacy of the intensive LMB-86 chemotherapy regimen. The median CD4 cell count was 236 x 106/l. 32 tumors were of the Burkitt type and 21 were Burkitt-like. All patients had stage IV disease with bone marrow involvement in 40 and central nervous system disease in 37. The LMB-86 regimen combined: (1) cytoreductive phase, with low dose cyclophosphamide, vincristine and steroids; (2) induction phase, with 2 consecutive courses of COPADM with high dose (8 g/m2) methotrexate (MTX); (3) consolidation phase with two courses of CYVE with high dose cytarabine and etoposide; (4) maintenance phase, with four courses combining previous drugs with lower dosage.
Thirty eight patients (71.7 %) achieved complete remission after the induction phase. With a median follow-up of 74.1 months (range, 8–153.1), 11 have progressed on therapy or relapsed. The median survival was 14.2 months and 32 patients have died. Most of deaths were due to BL (n=17, 53.1%), 5 (15.6%) to treatment toxicity, 7 (21.9%) to AIDS and 3 (9.4%) to other causes. The 1-year and 2-year estimate survival were 51% (95% CI, 44.1%–57.9%) and 47% (95% CI, 40.1%–53.9%), respectively (figure). Median disease free survival (DFS) was 41.7 months (range, 11.5-not reached) with a 2-year estimate DFS of 59.3%. Using the univariate analysis, four baseline covariates were associated with shorter survival: CD4<200 x 106/L (HR 3.3; 95% IC, 1.6–6.6), CD8 <1500 x 106/L (HR 2.5; 95% IC, 1.1–10), "B" symptoms (HR 3.6; 95% IC, 1.1–11.9), and ECOG score > 2 (HR 2.9, 95% IC, 1.3–6.4). No other HIV covariates, lymphoma baseline data or demographic data were associated with outcome. Using multivariate analysis only association with low CD4 count was significant (p=0.03).
Intensive chemotherapy regimen (LMB-86) containing high dose MTX and cytarabine is highly efficient in stage IV AIDS-related Burkitt’s lymphoma. Toxicity is high but acceptable with regard to the best overall survival reported to date.
Figure Figure
A Severe Case of Delayed Haemolytic Transfusion Reaction in a Sickle Cell Disease Patient: Immuno-Haematological Study, Cytokine Transcripts and Lymphocyte Subsets Analysis.
Authors: Noizat-Pirenne France , Ansart-Pirenne Helene , Plonquet Anne , Chadebech Philippe , Habibi Anoosha , Bachir Dora , Galacteros Frederic , Bierling Philippe 
Published: October 2019

Abstract
Background: Delayed haemolytic transfusion reaction (DHTR) may be a life-threatening complication in sickle cell disease (SCD) patients. DHTR is characterized by a marked drop in hemoglobin (Hb) and is frequently accompanied with intensification of the disease symptoms. Pathogenesis of DHTR is not completely understood as autologous RBCs are probably destroyed and allo-antibodies against transfused RBCs in the course of the accident are not always detected. Here we describe a case of serious DHTR and analyse lymphocyte subsets and cytokine transcripts.
Case report: A 33-year-old man with SCD was scheduled for hip replacement. He was poly-immunized (anti-RH2, -RH23, -RH30, -FY1, -FY3,-MNS3, -YT2) and had history of 2 DHTR. He received 7 units of crossmatch-compatible blood at day 0 of surgery. On days 5 and 8, sera were still compatible with samples of units received at day 0. Direct antiglobulin test (DAT) and eluate were negative. Hb remained stable at 6 g.dl−1. On day 14, the patient presented pain, fever and signs of hemolysis including a drop in Hb to 3.5 g.dl−1, LDH at 12460 U per L, bilirubin at 111 μmol/L and renal failure. Serological and eluate evaluation revealed the presence of antibodies against all RBCs tested (including units previously transfused at day 0), DAT positive with anti-C3 and anti-IgG. Hb dropped to 2.5 g.dl−1, the patient presenting neurologic symptoms. Because of the life-threatening anemia, he received 4 units that were compatible only with the known antibodies, associated with corticoids and cyclophosphamide. An anti-MNS5 was finally detected explaining partly the positive reactions against all RBCs tested. Then, additional U-negative units were transfused. The patient gradually improved symptomatically and was discharged from the high dependency unit on day 30. Hb level reached 6 g.dl−1. As compared to day 0, vigorous expansion (ten times) of Natural Killer subset (CD56+, CD16+) was observed on day 14 during hemolysis. This expansion was correlated to an increase of IL-10 transcripts whereas IL-2 and IFNγ transcripts were not detected. After treatment (day 32) lymphocyte subsets returned to the day 0 level and IL10 transcripts disappeared.
Conclusion : This case report confirms that DHTR can be induced by transfusion of crossmatch-compatible units. In this poly-immunized SCD patient, transfusion has elicited production of auto-antibodies. The observed expansion of Natural Killer cells during the hemolysis suggests that Natural Killer cells could participate, through an ADCC mechanism, to the destruction of both transfused and autologous RBCs. The involvement of IL-10 on Natural Killer FcγRIIIa receptor expression and Natural Killer cytotoxicity will be discussed.
ENMD-981693 Is an Orally-Active Kinase Inhibitor with Activity towards Human Hematologic Cancers In Vitro and In Vivo.
Authors: Bray Mark R. , Fletcher Graham C. , Denny Trisha A. , Xu John , Chen Xiaoru , Burke Patricia A. , Franklin Wanda , LaVallee Theresa M. , Minden Mark D. , Sidor Carolyn F. 
Published: October 2019

Abstract
The clinical success of Gleevec (imatinib) for chronic myelogenous leukemia has demonstrated that small-molecule inhibitors of specific kinases can be developed into effective oncology therapies. However, the rapid development of resistance in leukemic cells to drugs such as Gleevec and the limited therapeutic indications addressed with these molecules suggests that considerable opportunity exists for new inhibitors with a distinctive spectrum of activities against multiple kinase targets. ENMD-981693 is a novel, orally-active molecule that was discovered through a screening effort directed towards Aurora kinases, a family of serine/threonine kinases that are essential for mitotic progression. ENMD-981693 is selective for the Aurora A isoform, with an IC50 value of 25 nM, compared to an IC50 value of ~700 nM for Aurora B. The activity of ENMD-981693 was evaluated against a panel of 100 recombinant kinases, and the compound was shown to inhibit a broad range of tyrosine kinase targets including Flt3, CSF1R, Lck, JAK2, and c-Kit. ENMD-981693 inhibited the in vitro growth of human hematopoietic cancer lines including MV4;11, K562, THP-1, Jurkat, TF-1, U937, and HL-60 with IC50 values ranging from 0.04 – 21 μM. ENMD-981693 was shown to induce G2/M cell cycle arrest followed by apoptosis in U937 cells, without induction of the endo-reduplication phenotype (≥4N DNA content) associated with Aurora B-acting inhibitors such as MK-0457 (VX-680) and AZD1152. Primary cells derived from AML patients were sensitive to treatment with ENMD-981693 in vitro, resulting in IC50 values from 0.2 – 6.0 μM. Sensitivity of primary CML samples was more variable in in vitro cytotoxicity assays, with IC50s in the range of 0.1 – 40 μM. ENMD-981693 shows significant antitumor activity and is well tolerated in xenograft studies, with no weight loss or morbidity observed in administration schedules of up to 100 mg/kg bid or 200 mg/kg qd, given continuously for more than 30 days. Results from in vivo efficacy studies with ENMD-981693 using the MV4;11 xenograft model will be described. In conclusion, ENMD-981693 is a novel kinase inhibitor with potent activity towards a number of targets important in hematologic cancers.