bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Research of Autologous Hematopoietic Stem Cell Transplantation for Hematological Malignancies and Solid Tumors.
Authors: Huang Zhen-qian , Zhang Dong-hua , Tan Huo , Zhou Cheng-zhi , Liu Dan , Zhang Huan-zhu , Zhang Jie-xia , Huang Wei , Liu Wen-li 
Published: October 2019

Abstract
Objective: To evaluate the therapeutic effect of autologous hematopoietic stem cell transplantation (AHSCT) on hematological malignancies and solid tumors.
Methods: 20 patients with median age of 33.4±11.3 (18–50) years received AHSCT, 7 of them were acute non-lymphoblastic leukemias (ANLL)(CR1 5, CR2 1, refractory/relapse 1), 2 were acute lymphoblastic leukemia (ALL)(CR1 2), 1 was chronic myelogenous leukemia (CML-CP2), 1 was chronic lymphoblastic leukemia(CLL-NR), 6 were malignant lymphoma (CR1 2, CR2 2, NR 2), 1 was multiple myeloma, 1 was breast cancer relapsed after resection 10 years and lung and bone metastases, 1 was small cell lung cancer. 2 or 3 of following agents: Cytarabine(Ara-C)3–4g/m2, Cyclophosphamide (CTX) 4–6g/m2, Etoposide (VP-16) 0.5–1.0g/m2, Semustine (me-CCNU) 300mg/m2, Melphala n(Mel) 140mg/m2, Thiotep a (TSPA) 600mg/m2, Carboplatin (CBP) 1.0g/m2, were combined as conditioning regimen in all patients. Among them 2 patients with ALL accepted additional total body irradiation (TBI).
Results: All the patients have reconstituted bone marrow hematopoiesis after transplantation. None of them had the transplantation-related mortality. Among 20 cases, 15 achieved disease free survival (DFS) follow-up 36.5(2–106) months.
Conclusion: AHSCT might represent an effective approach for the treatment of some patients with chemosensitive solid tumor who are complete remission or part remission. Without compatible donors, patients with leukemia and malignant lymphoma at CR1 stage could receive AHSCT to reduce relapse and increase disease-free survival. It is suggest that have a obvious survival benefit from AHSCT.
Use of Complementary and Alternative Medicine (CAM) by Patients with Myeloma or Lymphoma.
Authors: García-Nieto Antonia , Capote F.J. , Martín-Reina M.V. , Bailén A. , Fernández-Valle M.C. , Gil J.L. 
Published: October 2019

Abstract
The use of complementary and alternative medicine (CAM) is wide-spread among cancer patients. Few studies have investigated the use of CAM by patients with haematological cancer patients in Europe.
OBJECTIVE: To investigate the distribution and patterns of CAM use by patients with myeloma or lymphoma.
PATIENTS AND METHODS: 103 patients with lymphoma and 23 with myeloma (72 male and 54 female) they have responded a questionnaire on diverse aspects of the use of CAM.
RESULTS: Ninety-six patients (76.1%) recognize to have used or to use some type or product CAM: Matricaria chamomilla L. (75,3%), Tilia vulgaris (57.4%), green tea (19.8%), Valeriana officinalis L (17.4%), Royal Jelly (17.4%), soya (16.6%), Brewer’s Yeast (7.9%), wheat germ (6.3%), ginseng (6.3%) and aloe vera (6.3%); Cat’s Claw, Hypericum Perforatum (St. John’s Wort), echinacea, grape seed, milk thistle (Carduus marianum), graviola and marijuana (less of 5%). Forty-nine patients (38.8%) recognize to have practiced or to practice oration (23.8%), relaxation (11.9%), oils massages (9.5%), meditation (6.3%), imposition of hands (3.9%) and yoga (3.9%); music therapy, homeopathy, Shiatsu, acupuncture, therapies through of the movement and the dance, guided imagination, psychotherapy, chiropractic and consult with healer (less of 3%). Visualization, hypnosis, biofeedback, chromotherapy, reflexology, or therapies through humour have not talked about or through Internet. They recognize to look for a complement for the traditional medicine (29.6%), to fight the indirect effect (17.4%) or to have control on the own disease (16.6%) not being felt impassive (23.8%); to content the family (3.1%) or to think that its treatment will be faster (21.4%) is other reasons. In 3.9% they tried to replace the traditional medicine. Only the 30.1% “complementary and alternative medicines” knew the meaning the terms. The 62.6% did not know the qualification of the personnel who sells products or applies treatments to him MAC and 36.6% not informs its doctor that take CAM. Sixty-one percent consider that the public system would have to finance this type of practices.
COMMENTARIES: This study contributes data on the use of therapies MAC by patients with myeloma or lymphoma in Spain. The professionals we must make the effort necessary to improve our knowledge of the MAC and the formation of the patients; the MAC that demonstrate to their effectiveness and security would have to be able to integrate themselves to the care of the patients.
Health-Related Quality of Life (HRQL) in Children with Severe, Chronic Immune Thrombocytopenia (cITP) Treated with Rituximab.
Authors: Parsons Susan , Bennett Carolyn , Mahoney Donald , Olson Thomas , Sawaf Hadi , Moore Theodore , Loh Mignon , Buchanan George , Neufeld Ellis 
Published: October 2019

Abstract
Background: A subset of children with cITP is at increased risk for severe bleeding and functional limitations. We evaluated the HRQL of children with cITP as part of a multicenter, open label Phase I/II clinical trial of four weekly doses of Rituximab, evaluated for response at 12 weeks. Responders had a ≥ 50,000/mm3 platelet count over weeks 9–12 without other supportive therapy.
Methods: All participating parents were invited to complete the Child Health Ratings Inventories (CHRIs) at baseline and 12 wks. The CHRIs, a generic HRQL questionnaire, contains 20 items, forming four domains in the areas of physical, role, and emotional functioning, and school. Each item has a five-point Likert response scale. Domain scores range from 0–100, with higher scores connoting better functioning. Of the 36 study participants, 24 parents opted to participate in the HRQL evaluation; 22 of 24 (91%) completed both the baseline and 12-week assessments. The baseline clinical profile and 12-week Rituximab response rates of HRQL participants and non participants (n=12) were compared. Potential clinical covariates (e.g., duration of illness, worst bleeding score, platelet count, number of prior therapies) were examined in a univariate analysis (UVA) with baseline HRQL domain scores. Regression analyses (MVA) adjusting for age and gender were used to assess the effects of treatment response and clinical covariates on the mean change in scores between baseline and week 12.
Results: While HRQL participants had more previous treatments and lower platelet counts than nonparticipants, their clinical profile was otherwise similar; Rituximab response rates did not differ. Mean HRQL domain scores (standard deviation) at baseline were as follows: physical-52.1 (36.2); role-78.6 (23.7); emotional-63.4 (18.3); school-64.1 (25.8). Lower platelet count and greater number of prior therapies were significantly associated with worse baseline HRQL scores on UVA. By week 12, 36% (8/22) responded to Rituximab. Clinically meaningful improvements in HRQL scores (≥ 0.5 standard deviation improvement) were observed in responders; no change was detected in non-responders. In MVA, responder status contributed the predominate effect on the HRQL change scores, with the greatest improvement noted in emotional functioning (p=.002). No other clinical variables emerged in this limited sample size.
Conclusions: The pattern of parent-reported HRQL scores for these children with severe cITP mirrored scores from other severe, pediatric health conditions. Significant improvements in HRQL were observed among Rituximab responders over the 12-week period while non-responders had no change. Further overall characterization of HRQL in the cITP pediatric population is needed.
Role of Atypical p50:p50:Bcl-3 NFκlB Complex in Differentiation of Erythroid Cells.
Authors: Sawyer Stephen , Chen Jingchun 
Published: October 2019

Abstract
We recently reported that mouse and human primary erythroid progenitor cells and erythroid cell lines synthesize and respond to Tumor Necrosis Factor-alpha (TNF-α). The nuclear transcriptional control complex, NFκlB is central in signaling downstream from TNF-α; so we began to study the function of NFκlB in erythroid cells. We made three very interesting initial findings: 1) first we found that NFκlB binding to DNA increased very slowly in HCD57 erythroid cells treated with erythropoietin (EPO, the hormone required for red blood cell development). An inhibitory effect of adding a neutralizing antibody to TNF-α on EPO-stimulated NFκlB DNA suggested this increase in NFκlB was due to TNF-α rather than direct EPO signaling. 2) We also found that NFκlB binding to DNA increased 10-fold or greater during erythroid differentiation. We found greatly increased NFκlB DNA binding in HCD57 cells that differentiated due to over-expression of JunB, F-MEL induced by DMSO, or human UT7-EPO or murine HCD57 cells induced to differentiate with hemin. 3) Surprisingly, we found that the NFκlB DNA binding complex in mouse primary erythroid cells and the erythroid cells lines tested was almost exclusively composed of the atypical p50/p50/Bcl3 NFκlB rather than the canonical p65/p50 or the non-canonical p65/p52 NFκlB. When we begin to study the biological significance of this atypical NFκlB in EPO-mediated erythroid differentiation in vivo using genetic tools, we found marked deficiencies in the development of erythroid cells in either the nfkb1−/− mice (p50−/−) or the bcl3 −/− mice. The nfkb1−/− mice were mildly anemic. The number of red blood cells in the circulation of these mice was statistically lower than in control mice. The number of CFU-e was also reduced in nfkb1−/− mice. Using the Ter-119 and CD71 staining method, we noted that proerythroblasts and immature erythroid cells increased and mature erythroblasts decreased in either non-anemic bone marrow or anemic spleens of nfkb1−/− mice. Forward scatter of Ter-119+ cells also showed an increased size of the average immature erythroid cell in the bone a marrow of nfkb1 −/− mice, suggesting a block in differentiation and continued cell cycling of the immature erythroblasts. Similar erythroid defects were observed in the spleens of anemic bcl-3−/− mice. nfkb1−/− mice and bcl-3−/− mice are also apparently unable to produce new reticulocytes as effectively as wild type mice after induction of anemia. Our working hypothesis is without expression of either p50 or Bcl-3 NFκlB proteins, immature erythroid cells continue to proliferate and ineffectively differentiate. In summary, the atypical p50/p50/Bcl-3 NFκlB complex appears necessary for maximal differentiation of immature erythroid cells.
Fusion to Vp16 Converts MEIS1 into an Oncoprotein That Immortalizes Progenitors and Causes AML in the Absence of Coexpressed Hox Genes: Hoxa7 and Hoxa9 Induced Further Stem Cell Gene Transcription in Vp16MEIS1 Progenitors.
Authors: Wang Gang G. , Pasillas Martina P. , Kamps Mark P. 
Published: October 2019

Abstract
MEIS1 and Hoxa9 are homeobox transcription factors that promote self-renewal in hematopoietic progenitors. MEIS1 does not induce leukemia, but cooperates strongly with Hoxa9 to produce acute myeloid leukemia (AML). Previously, we demonstrated that Hoxa9 blocks differentiation of myeloid progenitors that do not express MEIS1 and do not induce leukemic. Coexpression of MEIS1 causes transcription of genes that segregate with the leukemia-initiating subset of human AML blasts, such as CD34 and FLT3. We designate these genes as leukemic stem cell genes, or LSC genes. MEIS1 promoted LCS gene transcription by a mechanism that requires interaction with PBX and DNA, and that also requires a short MEIS1 C-terminal transactivation domain (CTD). Here we use a dominant transactivating or transrepressing form of MEIS1 to determine whether the activation or repression function of Pbx:MEIS1 complexes is sufficient to cause myeloid leukemia in combination with coexpressed Hoxa9. Surprisingly, fusion of MEIS1 to the Vp16 transactivation domain (but not the engrailed transrepression domain) produced an autonomous oncoprotein that immortalized progenitors and caused myeloid leukemias without the need for coexpressed exogenous or endogenous Hox genes. Like MEIS1, Vp16MEIS1 required binding to Pbx and DNA for immortalization; however, the CTD was not necessary in the context of Vp16MEIS1. This suggests that the CTD participates in target gene activation in AML blasts, a function replaced by Vp16 in its absence. Retroviral expression of Hoxa9 or Hoxa7 induced a further, strong, transcriptional upregulation of LSC genes in Vp16MEIS1 progenitors and elevated their leukemic potential to the level of bona fide AML blasts. These data suggest that transactivation is the essential function of Pbx:MEIS1 complexes in AML, and that HOX proteins cooperate with Pbx:MEIS1 complexes to activate transcription of early progenitor genes whose expression is required for human AML.
Human CD4+ CD25high Regulatory T Cells Inhibit Myeloid but Not Plasmacytoid Dendritic Cells Activation.
Authors: Houot Roch , Perrot Ivan , Durand Isabelle , Garcia Eric , Lebecque Serge 
Published: October 2019

Abstract
CD4+CD25+ regulatory T cells (Treg) are essential negative regulators of immune responses. However, the mechanisms of immune suppression and the spectrum of cells they target remain incompletely defined. In particular, although Treg directly suppress conventional T cells in vitro, they might also affect antigen presenting cells (APC).
Here, we studied the maturation of human myeloid (mDC) and plasmacytoid (pDC) dendritic cells activated with Toll-like receptor (TLR) ligands in the presence of CD4+ CD25high regulatory T cells in vitro. T cells and DC subsets were purified from normal human peripheral blood. LPS, CpG ODN 2216 and R-848 were used to trigger the maturation of mDC, pDC or both through TLR4, TLR9 and TLR7/8 respectively. Preactivated CD4+ CD25high Treg had no effect on the maturation of pDC. Conversely, they strongly suppressed TLR-triggered mDC costimulatory molecules up-regulation, pro-inflammatory cytokines secretion and their antigen presentation capacity, as opposed to conventionnal T cells (Tconv). At a ratio of 3 Treg for 1 DC, the percentage of mDC acquiring CD80 was reduced 5 fold (from 75% to 16%) while the Mean Fluorescence Intensity was decreased by approximately 65% for CD80 and 35% for CD86 after LPS stimulation and by 50% and 20% after R-848 stimulation. Furthermore, Treg dramatically decreased the secretion of IL-12p40, TNF-α, and IL-6 by mDC (95%, 93% and 50% average inhibition respectively) after LPS activation and to a lesser but still significant extent (38%, 35%, and 38% average inhibition respectively) after R848 stimulation. Finally, we found that Treg-conditionned mDC had a reduced ability to trigger naïve T cell proliferation in a mixed leukocyte reaction.
Suppression of mDC activation by Treg appeared to require cell-cell contact. Moreover, the inhibition of pro-inflammatory cytokines secretion, but not of phenotypic maturation, was almost completely restored using an anti-IL10 receptor monoclonal antibody, but not anti-TGFβ nor anti-CTLA-4 blocking antibodies. Those data suggest that Treg prevent the co-stimulatory molecules up-regulation on mDC through contact dependent mechanisms, while the modulation of cytokines secretion appears to be largely mediated by IL-10.
Overall, our results provide the first evidence of a direct inhibition of human mDC but not pDC maturation by CD4+ CD25high Treg. Therefore, by restraining the maturation of mDC, human Treg may enlist those cells for the initiation and the amplification of tolerance in vivo.
Treatment with Rituximab, CHOP and Highly Active Antiretroviral Therapy (HAART) in AIDS-Related Diffuse Large B-Cell Lymphomas (DLBCL). Study of 60 Patients.
Authors: Ribera Josep-María , Oriol Albert , Morgades Mireia , González-Barca Eva , Miralles Pilar , Lopez-Guillermo Armando , Lopez Andres , Xicoy Blanca , Abella Eugenia , Gardella Santiago , García Marta , Bargay Joan , Perez-Equiza Katy , Briones Javier , Rodriguez Lluis , Provencio Mariano , Escoda Lourdes , Soler Alfons , Canales Miguel , Asensio Antonio , Romero Antonio , Ferrer Secundino , Feliu Evarist 
Published: October 2019

Abstract
Background and objective. Rituximab and CHOP (R-CHOP) is the most employed treatment for DLBCL, but pts with AIDS-related lymphomas are usually excluded from clinical trials. The objective of this open, prospective multicenter trial is to evaluate the feasibility, efficacy and toxicity R-CHOP and HAART in AIDS-related DLBCL.
Patients and methods. Between April 2001 and July 2005, 60 consecutive HIV-infected pts with newly diagnosed DLBCL were included in 20 Spanish hospitals. HAART was given to all patients from diagnosis if they were not already receiving it. Six cycles of R-CHOP were administered, IT CNS prophylaxis (MTX, ARA-C and hydrocortisone) was given in every cycle to all patients. G-CSF support was recommended Response to chemotherapy, toxicity, OS and DFS for complete responders were recorded.
Results. Median age 42 yr (range 26–64), 49 (82%) males, 30 (50%) with previous known diagnosis of HIV infection (median from dx HIV to NHL 10 yr, range 0.5–19). Median CD4 lymphocyte count 152/mL (range 0–905), median HIV load 19x103 copies/mL (range 0–2x106). 36 pts were receiving HAART at the time of NHL dx (median 3.5 yr, range 0.5–9). Extranodal involvement 43 (72%), stage III-IV 38 (63%) and 36/56 had intermediate-high or high age-adjusted IPI score. 10 patients are under treatment, 1 (2%) withdrawal, 6 (12%) induction death (infection 3, hepatic failure 2, multiorgan failure 1), 10 (20%) resistant, CR 33 (66%). After a median follow-up of 2 yr, 2-yr survival probability was 63% (95%CI 50–76). The probability of remaining alive and in first CR at 2 yr for complete responders was 89% (95%CI 77–100). Three patients died in first CR (opportunistic infection, sudden death and violent death) and no relapses have occurred to date. Virologic and immunologic responses to HAART at 6 months after the completion of treatment were maintained or achieved in 17/21 (81%) and 14/22 (64%) of patients, respectively. Out of 245 R-CHOP cycles analysed the most frequent grade II-IV toxicities were infections (30, 12%), gastrointestinal (21, 9%) and neurologic (5, 2%).
Conclusion. In patients with AIDS-related DLBCL the combination of HAART and R-CHOP is feasible and effective. In this trial the response rate and survival are comparable to those obtained in immunocompetent patients treated with R-CHOP.
Time to Treatment Failure (TTF) and FLIPI Correlate Well with Survival and Are Independent Variables in Stage IV Indolent Follicular Lymphomas (IFL).
Authors: Fayad Luis , Pro Barbara , Liu Qi , Hess Mark , Hagemeister Fredrick , Romaguera Jorge , Samaniego Felipe , Cabanillas Fernando , Rodriguez Alma , Younes Anas , Wang Michael , McLaughlin Peter 
Published: October 2019

Abstract
BACKGROUND: The FLIPI score has been shown to predict survival in FL pts. Previous studies have suggested that type of treatment, and quality of response may not affect survival in pts with stage IV IFL. We address here the significance of TTF and quality of response as prognostic factors for survival in stage IV IFL.
METHODS: We reviewed the records of 580 pts with stage IV IFL treated from 1972- to 2002 with anthracycline containing regimens +/− rituximab. Demographics: male 51%, age 60 28%, Hgb<12 17%, high LDH 23%, 5 or more nodal groups 66%, BM+ 93%, FLIPI 3 or more 76%.
RESULTS: With a median f/up of 7 years
Response <PR (n=17) PR (n=86) CR (n=477) % dead 88 74 34 Median OS (mos) 19* 56* 185* TTF <1yr (n=60) 1–2yr (n=88) >2yr (n=432) % dead 85 53 33 Median OS (mos) 25* 76* 191* *p=0.001 % ORR (% CR) TTF (mos) Median OS (yrs) FLIPI<3 (n=151) 98 (89) 84 20.5 FLIPI≥3 (n=429) 96 (80) 44 10
Regression analysis for survival showed that both TTF and FLIPI correlated well with survival and were independent of each other (p<0.00001).
CONCLUSION: As expected, FLIPI <3 correlated with longer survival in IFL treated with anthracycline containing regimens. Interestingly, achievement of CR, longer response duration as measured by TTF also correlated with longer survival.
Meta-Analysis of Impact of Epoetin Alfa Versus Darbepoetin Alfa on Blood Transfusion Requirements.
Authors: Lefebvre Patrick , Moyneur Erick , Zilberberg Marya , Duh Mei S. , Aggarwal Jyoti , Piech Catherine Tak 
Published: October 2019

Abstract
Background: Epoetin alfa (EPO) and darbepoetin alfa (DARB) are commonly used for the treatment of chemotherapy-induced anemia (CIA). To date, three randomized head-to-head studies have compared EPO dosed 40,000 Units once weekly (QW) and DARB dosed 200mcg once every two weeks (Q2W). As transfusion results across these studies were inconsistent a meta-analysis was undertaken to provide a pooled estimate of the comparative difference in red blood cell transfusion rates between DARB and EPO treatment groups.
Methods: Demographic and transfusion rate data were extracted from the three publicly available head-to-head comparison studies (pooled N=940 for DARB and N=933 for EPO). Odds ratios, risk ratios and risk differences of transfusion rates from week 1 to the end of treatment between DARB and EPO groups were analyzed using both fixed- and random-effects meta-analysis methods; the latter incorporated between-study variation in addition to within-study variation. A multivariate logistic regression model weighted by the number of patients in each study arm and including population-level characteristics from each study arm, was conducted to isolate the treatment effect on the risk of transfusion after controlling for differences in baseline characteristics between DARB and EPO patients.
Results: Fixed- and random-effects models generated similar results (p>0.42 for homogeneity test across studies), both demonstrating that the DARB Q2W group had a statistically significantly higher transfusion rate than the EPO QW group. Using the random-effects model, the odds ratio of transfusion in the DARB group was 1.28 of that in the EPO group (95%CI: 1.03– 1.59). The corresponding risk ratio and risk difference were 1.21 (95%CI: 1.02–1.43) and 4% (95%CI: 0.3%–8%), respectively. Multivariate regression analysis further confirmed DARB Q2W had a higher transfusion rate compared to EPO QW, after controlling for age, baseline hemoglobin and the proportion of breast cancer patients (adjusted odds ratio=1.45, 95%CI: 1.10–1.91).
Conclusion: This meta-analysis demonstrates that, in patients with CIA, EPO 40,000 units QW is more effective at reducing RBC transfusion requirements than DARB 200 mcg Q2W.