bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Stem Cell Transplantation For Primary Refractory Hodgkin's Disease: Ablative Vs Reduced Intensity
Authors: Ozcelik Tulay , Guvenc Serkan , Hindilerden Fehmi , Hasbal Baris , Serefhanoglu Songul , Küçükkaya Reyhan , Arat Mutlu 
Published: October 2019

Abstract
Minority of patients with Hodgkin’s lymphoma (HL) are primary refractory or relapse very early after first-line chemotherapy or even after high-dose chemotherapy (HDCT) and autologous HSCT. The dismal outcome of these patients was shown by many previous studies. We evaluated the role of allogeneic stem cell transplantation in this setting. We retrospectively analysed 6 consecutive patients (med age 45) with primary refractory advanced stage Hodgkin’s lymphoma transplanted between 2011-2013. The median time from initial diagnosis and from autologous HSCT to allogeneic transplantation was 44.1 mo.s and 12.4 mo.s, respectively. The donor sources were sibling in 4, unrelated in one and haploidentical in 1. The conditioning regimen was myeloablative (BU-CY) in 3 and reduced intensity (Flu-Mel±ATG) in 3 adjusted according to their age and comorbid conditions. All of them received peripheral blood stem cells. Engraftment failure was not observed. None of them were complicated with VOD or other early complications of HSCT. Day 100 transplantation related mortality was 16.7% (1 patient). The patient succumbed to carbapenemase+ klebsiella pneumonia sepsis on day +11. Median follow up of the surviving patients was 14.65 months (range, 6-26). At the last follow up 3 of them were in CR, one patient had progression after HSCT and achieved stable disease with brentuximab and DLI. One patient died from acute abdominal infection on +187 while in CR. Only one patient was complicated with both acute and chronic GVHD (unrelated HSCT). The myeloablative regimen was tolerated well and the patients achieved durable remission. The expired patients were both in RIC arm. Although the number of transplanted patients is low we can conclude that allogeneic HSCT using myeloablative regimen is safe and effective in short term. Primary refractory HL patients should be evaluated for allogeneic HSCT, as upfront or following failure of autologous HSCT and HDCT. Ablative regimen is tolerated as well as RIC, and more effective than allo RIC for disease control in the light of our current limited cohort.

Disclosures:
No relevant conflicts of interest to declare.
Autologous Stem Cell Transplantation For Acute Leukemias In Suzhou (China): Similar Outcome In CR1 Patients Compared With European Group For Blood and Marrow Transplantation (EBMT) Results: A Pair-Matched Analysis
Authors: Chen Jia , Lu Yin , Labopin Myriam , Wu De Pei , Mohty Mohamad , Gorin Norbert Claude 
Published: October 2019

Abstract
The first affiliated hospital of Soochow University initiated a program of stem cell transplantation for hematological malignancies in 2001 and has done until December 2011 a total of 70 autografts to consolidate acute leukemias (61 adults and 9 children).
The EBMT presently handles a registry with information on more than 450 000 transplants including over 100 000 transplants for Acute Leukemias, of which 22800 were autografts. In order to evaluate the outcome of patients transplanted in Suzhou and to compare it with results from the EBMT, we collected the necessary information on all patients transplanted in Suzhou and we did a pair matched analysis with patients reported to the EBMT registry.
The median age of the patient population autografted in Suzhou was 32 years (4-63). The median follow up was 34 months (1-136). 59 patients (47 AML, 12 ALL) were autografted in CR1 and 11 in CR2/3. The majority of patients received a non TBI conditioning (87%) and PB as a source of stem cells (87%). For those autografted in CR1, the interval from CR1 to transplant was 203 days (75-404). At 2 years, the OS, LFS, RI and NRM were 73±7%, 52± 7%, 44±8% and 5±3% for AML and 76±14%, 67± 16%, 33±17% and 0% for ALL. 48 adult patients autografted in CR1 from Suzhou were matched with 89 patients from the ALWP EBMT registry. Matching factors were age ± 3 years, Cytogenetics and the number of induction courses to reach CR1 (1 course versus more than 1). Patients from Suzhou were transplanted more recently ; the interval from diagnosis to transplant was longer (242 days vs 172 days, p<0.0001) and TBI was less frequently used (p= 0.004 ). By univariate analyses the results were: Suzhou versus EBMT: OS 76 ± 6 vs 69 ±5 % (p= 0.33), LFS 55 ± 7 vs 60 ± 5% (p= 0.44), RI 40 ± 7 vs 33 ± 5% (p= 0.27), NRM 4 ± 3 vs 7 ± 3% (p = 0.47). By multivariate analyses adjusting for interval from diagnosis to transplant, year of transplant and use of TBI, there was no significant difference for OS (HR: 0.65, 95% CI: 0.19-2.19; p=0.49), LFS (HR: 0.97, 95% CI : 0.44-2.15; p=0.95), RI ( HR: 1.02, 95% CI : 0.46-2.28; p=0.96) .
We conclude that the results from Suzhou are not statistically different from those obtained using the EBMT database. These findings as well as the observation in another study of similar outcomes following allogeneic transplants in China and within EBMT are important to consider when planning international multicenter randomized studies.

Disclosures:
No relevant conflicts of interest to declare.
Impact Of High Resolution HLA Mismatch On Outcomes Of Unrelated Peripheral Blood Stem Cell Transplantation
Authors: Park Silvia , Kim Kihyun , Jang Jun Ho , Jung Chul 
Published: October 2019

Abstract

Introduction
High resolution HLA disparity between donor and recipient affect transplantation outcomes of unrelated peripheral blood stem cell transplantation (PBSCT), however the importance of individual loci in a high resolution level still remains unclear. The purpose of current study was to examine the impact of high resolution HLA disparity on transplantation outcome.

Materials and methods
We retrospectively analyzed 104 pairs of donor-recipient, who received PBSCT from unrelated donors (MUDs) between January 2009 and August 2012 at the Samsung Medical Center. The result of high resolution typing of HLA-A, -B, -C and -DRB1 were reviewed. Clinical outcomes were evaluated in terms of acute/chronic GVHD, relapse and survival.

Results
All but 11 cases (89.4%) received serologically matched transplantation. Of the 104 pairs, mismatching at high resolution level was observed in 34 cases (32.7%), containing 1, 2, and 3 or more mismatches in 15 (14.4%), 14 (13.5%) and 5 (4.8%) cases. According to the HLA loci, mismatches were detected in 12 (11.5%), 10 (9.6%), 10 (9.6%) and 21 cases (20.2%) on HLA-A, -B- C, and DRB1 loci. There were no significant differences in the incidence of chronic GVHD between the 8/8 matched pairs and 7 or less/8 matched pairs. However, the incidence of grade II-IV acute GVHD was significantly higher in patients with HLA-A mismatch compared with those with full matched HLA-A (p=0.011), although it was not translated to differences in survival or relapse. Overall survival was significantly inferior in patients with mismatching on HLA-B loci (p=0.0399), and it was mainly attributable to increasing non relapse mortality (NRM) in these patients (p=0.0252).

Conclusion
The potential role of high resolution HLA disparity on the development of GVHD or transplant outcomes has not been confirmed in the present study, and further study with larger number is necessary. Of note, high-resolution mismatch on HLA-B might be associated with worse outcomes in unrelated donor PBSCT.

Disclosures:
No relevant conflicts of interest to declare.
CXCL9 Contributes To Chemotherapy-Induced Acute Intestinal Damage Through Proliferative Inhibition Of Epithelial Cells
Authors: Lu Huili , Liu Hongyu , Shen Jiaqing , Weng Shunyan , Qian Lan , Wu Mingyuan , Zhu Shunying , Yu Yan , Han Wei , Zhu Jianwei , Moldenhauer Anja 
Published: October 2019

Abstract
Apart from angiostasis and chemoattraction, CXCL9 can derange hematopoiesis by its influence on mesenchymal stroma cells. The receptor of CXCL9, CXCR3, is abundantly expressed intracellularly in epithelial cells, even though it is rarely present on the surface of these cells. Here, we hypothesized that CXCL9 influences the proliferative and degenerative activity of epithelial cells in vitro and in vivo. CXCL9 inhibited the proliferation of MCF10A cells in a dose-dependent manner. In vivo, rhCXCL9 caused an intestinal weight loss of 30% in normal mice (n=6, 0.59±0.05 g of rhCXCL9 treated mice versus 0.83±0.06 g controls, P = 0.0007 determined by 2-tailed student’s t-test). Intestinal epithelial cells of 5-Fluorouracil (5-FU) treated mice developed a 2.55 fold higher level of cxcl9 expression, indicating that CXCL9 may participate in a chemotherapy-induced damage of the intestinal epithelium. Neutralization of the up-regulated endogenous CXCL9 by anti-CXCL9 monoclonal antibodies accelerated epithelial regeneration determined by villi length (317.5±19.9 μm versus no-antibody control 283.7±17.1 μm, P < 0.001) and crypt depth (78.0±8 μm versus control 67.9±10.9 μm, P = 0.326). CXCL9 function was highly associated with p70 ribosomal S6 kinase (p70S6K) activation (50.0±2.2 MFI versus control 27.9±1.4 MFI, P = 0.007), which was reversed by anti-CXCR3 (31.4±5.7 MFI, n=4). CXCL9 downstreamingly stimulated TGF-β secretion of epithelial cells through the mTOR/p70S6K pathway (66.3±17.1 pg/mL versus on-treated control 39.8±12.2 pg/mL, P <0.05), which was reversed by anti-CXCR3 (46.8±21.6 pg/mL, n=8). That explains the anti-proliferative effect of CXCL9 on these cells. Our results strongly suggest that anti-CXCL9 may help to mitigate a chemotherapy-induced intestinal damage. The work was supported by the National Science Foundation China (81273576, 30801419, 30901873), and the German Academic Exchange Service (A/09/90104).

Disclosures:
No relevant conflicts of interest to declare.
TPO plus Tanshinone IIA has neural protective effect and this effect may be mediated via its receptor c-mpl and PI3K/Akt signaling
Authors: Yang Mo , Ye Jie yu , Li Su yi , Liang En yu , Meng Fan yi , Lian Qizhou 
Published: October 2019

Abstract
Thrombopoietin (TPO) is a growth factor for platelet/megakaryocytic lineage. Our previous study showed TPO has cardiac protective effect(Li et al, Circulation, 2006). TPO may also has a protective effect in neural cells. Tanshinone IIA (TIIA), isolated from Danshen (Radix Salviae Miltiorrhiza Bge), is a derivative of phenanthrenequinone, which has been widely used as anti-platelet and neural protection drug for stroke for many years in China. In this study, a hypoxic–ischemic encephalopathy model was established, followed by 2 hrs of hypoxia in 7-day-old neonatal rat pups. TPO (12.5 ug/kg) or/and TIIA (10 mg/kg) were administrated daily (IP) for two weeks. The severity of brain injury was estimated by the weight reduction of the ipsilateral cerebral hemisphere as compared to the contralateral hemisphere. There was significant less atrophy in TPO alone or TPO plus TIIA treated animals compared with that in controls at 7 and 21 days (P<0.05, n=8). The loss of neurons in the forelimb area of the cortex was also reduced after TPO or TPO plus TIIA treatment. NSE positive cells in the forelimb area of the cortex in the right hemisphere was significantly higher in the treatment group than that of the saline group (P<0.05, n=8). An improvement in sensory motor functions was also demonstrated after TPO or TPO plus TIIA treatment. Furthermore, TPO receptor (c-mpl) mRNA was identified in human cerebral hemispheres and cerebellum, and C17.2 cell line using RT-PCR. The expression of c-mpl protein was further confirmed in human cerebral hemispheres, hippocampus, cerebellum, brainstem and spinal cord using immunocytochemical staining. Its ligang TPO was also detected in human cerebrospinal fluids (n=10) by ELISA, and TPO mRNA was expressed in human cerebral hemispheres, cerebellum, and mouse neural stem cell line C17.2 by RT-PCR methods. TPO showed an anti-apoptotic effect on C17.2 cells by the AnnexinV/PI assay. Moreover, TPO activated PI3K/Akt signaling pathway which was demonstrated by Western blot. The Akt activation by TPO was inhibited by the PI3-kinase inhibitor LY294002. This study provided the evidences showing that TPO or TPO plus TIIA has neural protective effect and this effect may be mediated via its receptor c-mpl, then activated PI3K/Akt signaling.

Disclosures:
No relevant conflicts of interest to declare.
Imatinib mesylate has an inhibitory effect on hematopoiesis in a mice model
Authors: Ye Jie yu , Li Su yi , Liang En yu , Meng Fan yi , Chong Beng , Yang Mo 
Published: October 2019

Abstract
Imatinib mesylate (Gleevec or STI-571), a tyrosine kinase inhibitor, can potently block both platelet-derived growth factor (PDGF) receptor-α and β by inhibiting the receptor tyrosine kinase activity. Imatinib mesylate has been successfully used to treat patients with chronic myeloid leukemia (CML) and Ph positive acute lymphoid leukemia (ALL). However, a significant number of patients with imatinib mesylate treatment have developed neutropenia, thrombocytopenia and anemia (van Deventer, Hall et al. 2002). Our previous studies have demonstrated that PDGF/PDGFR plays an important role on thrombopoiesis, and blockage of PDGFR by imatinib inhibited the downstream signal pathway, which led to reduce of megakaryocyte production (Ye, et al. Haematologica, 2010). This may partially explain the imatinib-related thrombocytopenia. However, the role of imatinib on normal hematopoiesis remains to be investigated. In the present study, we identified the expression of PDGFR-β on the human megakaryoblastic cells: Meg-01, CHRF-288-11, Dami and M-07e, human erythromyeloblastoid leukemia cells: K-562 and human myeloblastic cells: HL-60 by RT-PCR, western blot and flow cytometry. We then demonstrated the effect of imatinib on normal hematopoiesis in the 8 wk old C57BL/6 mice model. Gleevec (25 mg/kg/day) dissolved in distilled water or water only were given orally for up to 2 wks. 15ul whole blood was taken from postorbital weekly to perform blood cell counts. The Gleevec -treated group showed a reduction of platelet count as compared to the control at day 14 (543.3±71.95×109/L vs. 330.0±62.23×109/L, n=5, P<0.05). Similarly, Gleevec caused a significant decrease in the number of white blood cells on day 14 (9.667×±0.8511×109/L vs. 6.080±0.8015×109/L, n=5, P<0.05). While no significant differences were found on red blood cell count between Gleevec and control groups. The mice bone marrow was harvested from each group to perform CFU assays. Gleevec significantly inhibited the formation of bone marrow CFU-MK (15.33±1.764 vs 3.333±0.6667, n=3), and CFU-GM(13.50±2.784 vs 6.333±0.7265, n=3) compared with the control. There were no significant differences found in CFU-GEMM and CFU/BFU-E formation between the Gleevec and control treatment. Our studies suggested that PDGFR were expressed on hematopoietic cells. Imatinib mesylate, an inhibitor of PDGFR, not only played an important role in malignant hematopoiesis, but also in normal hematopoiesis. Administration of Gleevec reduced white blood cells and megakaryocytes/platelets production, which implied its potential therapeutic role in treating myeloproliferative diseases, such as Essential Thrombocytosis.

Disclosures:
No relevant conflicts of interest to declare.
The Impact Of The Establishment Of a Hematology Telemedicine Consult Service In a Referral Center On Patients’ Travel Distance, Travel Cost and Satisfaction Scores
Authors: Yellapragada Sarvari Venkata , Hermosillo-Rodriguez Jesus , Sada Yvonne , Walder Annette , Sam Kathy , Mulchandani Alka , Hayes Teresa G , Jessica Davila A 
Published: October 2019

Abstract

Introduction
Travel cost and travel distance can decrease access to care. Telemedicine services can reduce patient travel distance and cost in subspecialty consult services. The impact of telemedicine services on travel distance and travel cost in hematology consult services has not been widely studied. We analyzed the impact of a hematology telemedicine consult service in the Michael E. Debakey VA Medical center (MEDVAMC) in Houston, Texas. The MEDVAMC provides subspecialty consult services for Community-based Outpatient Clinics (CBOC). Our hypothesis in this study was that the establishment of a hematology telemedicine clinic would reduce travel distance for the patient and travel pay made by the MEDVAMC for this specialty with high level of satisfaction among veterans.

Methods
We conducted a prospective cohort study of veterans enrolled in the hematology telemedicine clinic at the MEDVAMC from September, 2011 to June, 2013. Any veteran referred to or established in the hematology clinic was eligible to be enrolled in the telemedicine service if they lived closer to a CBOC than to the MEDVAMC. The telemedicine encounter included meeting with a hematologist, a social worker and/or nutritionist. Patients went to their assigned community clinic to connect with the hematology telemedicine service. Data on demographics and diagnosis (benign or malignant hematology condition) were collected. Outcome variables included travel distance, estimated travel cost and patient satisfaction scores with the telemedicine service. Cost of travel was defined as the estimated amount that the MEDVAMC reimburses eligible patients for their travel costs.

Results
The hematology telemedicine clinic enrolled 255 veterans during the study period. Among these patients, 195 (76%) had benign hematology conditions and 60 (24%) had malignant hematology conditions. 237 (93%) of patients were male, and 156 (61%) lived in a rural area. The mean travel distance saved was 64 miles (SD 11.5). This translated into an estimated average of 21 dollars of travel pay saved per patient. Out of all telemedicine encounters, there was a 42% survey return rate. In 94% of these surveys veterans reported they were satisfied with the visit and that they would recommend the hematology telemedicine program.

Conclusion
The establishment of a telemedicine consult service in a referral center decreased travel distance for patients and travel pay cost. Most patients that answered the feedback surveys reported they were satisfied and that they would recommend the program. Other studies looking at cost-effectiveness, and patient and disease-related outcomes will help understand further the impact and benefits of such a program.

Disclosures:
No relevant conflicts of interest to declare.
Prognostic CMR Parameters For Cardiac Complications In Large Cohort Of Well Treated Thalssemia Major Patients
Authors: Meloni Antonella , Tassi Cristina , Batzella Maria Grazia , Commendatore Francesca Valeria , Giannotti Giorgio , Serra Giuseppe , Keilberg Petra , Maggio Aurelio , Valeri Gianluca , Positano Vincenzo , Lombardi Massimo , Pepe Alessia 
Published: October 2019

Abstract

Introduction
Cardiac complications are the main cause of death in thalassemia major (TM) patients. Cardiovascular Magnetic Resonance (CMR) plays a key role in their management, assessing myocardial iron overload (MIO), biventricular function, atrial dimensions, and myocardial fibrosis. We evaluated the predictive value of CMR parameters for cardiac complications, including heart failure (HF), arrhythmias and pulmonary hypertension (PH).

Methods
We followed prospectively 537 white TM patients enrolled in the MIOT network. Fifty patients were excluded from the analysis because a cardiac complication was present at the time of the first CMR. All prognostic variables associated with the outcome at the univariate Cox model were placed in the multivariate model and were ruled out if they did not significantly improve the adjustment.

Results
At baseline the mean age was 29.5±9.0 years and 222 patients were males. The mean follow-up time was 58±18 months. After the first CMR only the 37.8% of the patients did not change the chelation regimen or the frequency/dosage.

Conclusions
We detected few cardiac events thanks to a MR-guided, patient-specific adjustment of the chelation therapy. Severe and homogeneous MIO, myocardial fibrosis and ventricular dysfunction identify patients at high risk of heart failure. Heart T2* doesn’t have any power in predicting arrhythmias while male sex and atrial dilation are independent prognosticators. Male sex, severe and homogeneous MIO, myocardial fibrosis and ventricular dysfunction identify patients at high risk of cardiac complications globally considered.

Disclosures:
No relevant conflicts of interest to declare.
Surveillance Of Healthcare Associated Infections In Hematology: Prospective Study About 237 Patients
Authors: Fares Salma , Lamchahab Mouna , Zerouali Khalid , Serhier Zineb , Benchekroun Said , Quessar Asmaa 
Published: October 2019

Abstract

Background
Immunocompromised children or adults patients are a population at high risk of infection, thus constituting a major cause of morbidity and mortality. They are 2 times more common in oncology and hematology patients (9-12%) than in not cancerous patients (6-7%).The incidence of hematology nosocomial infections (NI) is around 20%. Although data on NI are available, those about healthcare associated infections (HAI) are poorly studied.

Objective
Our aim was to define the incidence rate and risk factors of HAI of hematology patients over a period of 7 months from February to August 2012 in preliminary study to create a local register for HAI and establish strategies for hygiene and preventive policy of our unit.
Patients & methods
We took forward all aged over 18 patients hospitalized and monitored for hematologic malignancies in the adult and transplant unit at hematology and oncology center at the 20th August 1953 hospital in Casablanca. Informations were collected and validated by dealing doctors using a farm and data analysis was done by biostatisticians team using Epi Info software. Rates of HAI were calculated for patients- 1000 hospitalization day.

Results
Among this population of 237 patients, we diagnosed 183 HAI in 94 patients, witch 62.8% were followed for acute myeloid leukemia (AML). Incidence rate of HAI was 42.1% with confidence interval (CI) of 95% at [37.4-46.9%] against 29.9% for NI and incidence density of HAI by 1000 hospitalization day was 31.6 versus 24.6 for NI. Risk factors have implicated significantly neutropenia 87.4% (p<0.001), chemotherapy 83% (p<0.001) and temporary central catheter 60% (p<0.001). HAI were microbiologically documented in 41% witch bacteremia in 28%. Pneumonia was noted in the third of cases. Infection was of unknown origin in 25%. Germs isolated were mainly bacteria (93%), specially Staphylococci (32%) and Enterobacteriaceae (29%). Majority of our isolates have one or many antibiotic resistance.

Conclusion
Incidence rate of HAI was high in our study relative to NI, so they should be preferred because they’re covering a broader definition and therefore can be used as a quality indicator for prevention programs. Our study presented a preliminary step in the creation of a HAI register and the initiation of a prevention policy adjusted on ecological profile of our unit.

Disclosures:
No relevant conflicts of interest to declare.