bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eighteen Years Experience of Granulocyte Donations - Acceptable Donor Safety?
Authors: Axdorph Nygell Ulla , Sollén-Nilsson Agneta , Bjorkholm Magnus , Lundahl Joachim 
Published: October 2019

Abstract
Background. Granulocyte transfusions are given to patients with life-threatening infections, refractory to treatment. The donors are stimulated with corticosteroids +/- G-CSF. However, data regarding the donor’s safety is sparse. The objective was therefore to evaluate short and long term adverse events (AE) in stimulated donors.
Study design and methods. All consecutive granulocyte donors 1994-2012 were identified through our registry. Data were evaluated for the number of aphereses, stimulation therapy, AE, blood values post donation and recent status from the donation records.
Results. 154 volunteer donors were mobilized for 359 collections. Age at first granulocyte donation was 43 years (median; range 19-64 years). Follow-up was 60 months (median; range 0-229 months). The dose G-CSF per collection was 3.8 ug/kg body weight (median; range 1.6-6.0 ug/kg). Sedimentation agent was HES. Short term AE were mild. Blood values 4 weeks post donation with minor reductions/elevations mostly resolved in later donations. Fourteen donors were excluded from the registry due to hypertension (4), diabetes (2), atrial fladder (1), ca mammae (1), ca in situ urethra (1), MGUS (1), thrombosis (1), anaphylaxis (1), primary biliary cirrhosis (1), unknown (1). Three donors are deceased due to diabetes, acute myocardial infarction and unknown cause. Time from first donation to exclusion was 37 months (median; range 1-198). All donors except one were excluded/died at least 6 months after the first granulocyte donation.
Conclusion. No serious short term AE were observed. Due to the variability of diagnoses among excluded /deceased donors, we propose that it is less likely that granulocyte donations have a causative impact on these donors’ exclusion or death.

Disclosures
No relevant conflicts of interest to declare.
A Novel Protocol Decreased Incidence of Hepatic Veno-Occlusive Disease and Improved Results in Hematopoietic Cell Transplantation for Patients with b-Thalassemia Major
Authors: Li Chunfu , Pei Fuyu , Li Qi , Liao Jianyun , An Shengli , Wu Xuedong , He Yuelin , Feng Xiaoqin , Zhou Xiaohui , Shi Lei , Liu Huaying , Li Na , Xu Wenfeng , Tan Wanxia , Peng Zhiyong , Chen Jiaqi , Ren Yuqiong 
Published: October 2019

Abstract

Hepatic veno-occlusive disease (VOD) is a common complication of hematopoietic cell transplantation (HCT), especially patients with β-thalassemia major (TM). To estimate whether incidence of VOD recently decreased after using NF-08-TM protocol (NP), 311 TM-HCTs performed from February 2003 to June 2013 were analyzed. 241 patients received NP in or after 2009 and 70 received non-NP before 2009. VOD was diagnosed by Seattle criteria (SC) or Baltimore Criteria (BC). Patients were stratified by Nanfang (NF) criteria. A total of 31(10.0%) and 14 (4.5%) HCTs developed VOD (6 and 5 developed severe VOD) in SC and BC cohorts, respectively. The incidence of VOD was significantly lower in NP versus non-NP groups and in Class 2 versus Class 3 groups. Overall survival was significantly higher in NP versus non-NP cohorts. Rate of VOD in alternative donor transplant (ADT) was similar to that in matched sibling transplant (MST). Requirement of platelet and value of D-dimer significantly increased in the VOD patients. Our study showed the incidence of VOD significantly decreased in our center after using NP. ADT was similar to MST on rate of VOD. NF criteria of stratification can indicate occurrence of VOD. The SC can be more suitable criteria for early diagnosis.

Disclosures
No relevant conflicts of interest to declare.
Clinical Study of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: He Jun , Ding Jiahua , Ni Ming , Chen Baoan 
Published: October 2019

Abstract

To analysis the cytomegalovirus（CMV） infection rate and median time which the CMV-DNA was positive for the first time. Simultaneously, to demonstrete the risk factors associated with CMV infection and CMV disease distribution and mortality after allogeneic hematopoietic stem cell transplantation（allo-HSCT).A retrospective study among 108 patients with allogeneic hematopoietic stem cell transplantation allogeneic hematopoietic stem cell transplantation(allo-HSCT) was conducted during 1st Jan 2004 and 31stMar 2014 in Zhongda hospital.The infection rate of CMV was 52.78%(57/108), the median time of CMV infection was 44d, especially during 30d~100d. The univariate analysis showed that CMV infection rate was associated with the HLA-identical situation between the donor and recipient, whether the use of Anti-human thymus globulin(ATG) conditioning regimen, neutropenic period after transplantation exceeded 10d and graft-versus-host disease (GVHD). Multivariate analysis showed that CMV infection rate was associated with neutropenic period after transplantation which exceeded 10d and graft-versus-host disease (GVHD).The mortality of the patients who had CMV infection was 10/17 and the mortality of CMV interstitial pneumonia was higher. CMV infection was one of the most commonly happened infection after allo-HSCT.
To reduce the incidence of CMV disease and mortality, the best choice of Allo-HSCT was HLA-identical donor, ATG should be used during the process, and neutropenic period should be reduced less than 10 days. Moreover, it is necessary to strengthen the treatment of CMV infection actively.

Disclosures
No relevant conflicts of interest to declare.
Low Percent of Granzyme B Positive T-Regulatory Cells (CD4+CD25high) As a Predictor of Acute Graft-Versus-Host Disease (GVHD) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)
Authors: Drokov Mikhail , Parovichnikova Elena N. , Kuzmina Larisa A , Galtseva Irina , Vasilieva Vera , Savchenko Valeri G. 
Published: October 2019

Abstract
Introduction. Granzyme B is a serine protease commonly found in the granules of cytotoxic lymphocytes and natural killer cells. It is secreted with the pore forming protein perforin and mediates apoptosis in target cells. Granzyme B – mediated cytolysis is one of the regulatory mechanisms (together with IL-2 receptors (CD25)) by which T-regulatory cells (Tregs) influence on T-effectors cells. It is a well-known fact that Tregs participate in a pathogenesis of aGVHD and their amount after allo-HSCT inversely correlates with the probability of aGVHD incidence. No clinical data exist regarding the Granzyme B positive Tregs in this setting.
Patients and methods. Peripheral blood samples were collected in EDTA-tubes at day +30, +60, +90 after allo-HSCT and at day of acute GVHD onset from 27 patients with hematological malignancies (AML=12, ALL n=12, LPD=2, MDS =1; 6 with active disease, 21 - in CR) after allo-HSCT (from matched unrelated donor n=23, from matched related donor n=4; MAC = 10, RIC=17).
The anti-CD4-APC-Cy7, anti-CD25-FITC and anti-Granzyme B-PE (Becton Dickinson, USA) antibodies were used to determine T-regulatory cells population as CD4+CD25high. We did not include anti-FoxP3 antibodies as FoxP3 is not so specific in humans and particularly after allo-HSCT due to technical difficulties, several isoforms, FoxP3-positivity on activated nonregulatory CD4+ cells. CD4- lymphocytes (CD8+ and NK-cells certainly containing granzyme B) were used as internal positive control to define the percent of CD4+CD25highGranzymeB+ cells and gMFI (geometric mean fluorescence intensity) among the mononuclear cell fraction. 50000 of CD4+ cells were analyzed on a BD FACSCanto II (Becton Dickinson, USA).
Results. 11 patients (42%) have developed aGVHD (II-IV) at a median time of +26 day (8 - 88) after HSCT. The percent of CD4+CD25highGranzymeB+ cells among CD4+cells at day +30 after allo-HSCT in patients who never developed aGVHD was statistically higher (9,49±2,79; p=0.003) than in patients at day of aGVHD onset (3,8±1,78). It’s worth to note that in 4 patients who did not have signs of a GVHD on day +30 but developed it later (on day +40, +45, +74, +88), the percent of CD4+CD25highGranzymeB+ cells at day +30 was as low (3,38±1,47) as at day of aGVHD onset and significantly lower (p=0.003) than in patients who never developed aGVHD, thus predicting the occurrence of aGVHD in the future.
Conclusion Despite the fact that the analyzed group is small, we suggest that low relative amount of CD4+CD25highGranzymeB+ cells after allo-HSCT may contribute to the development aGVHD and even predict it onset. This fact, of course, needs further investigation.

Disclosures
No relevant conflicts of interest to declare.
Single Center Retrospective Comparison of Gvhd Preventive Regimens after Cy/Flu Minimal Intensity Allotransplantation
Authors: Ranganath Praveen , Robertson Michael J. , Abonour Rafat , Schwartz Jennifer E. , Farag Sherif , Wood Lisa l , Kiel Patrick , Nelson Robert 
Published: October 2019

Abstract
Graft-versus-host disease (GVHD) remains the 2nd leading cause of mortality—after relapse/progression following allogeneic hematopoietic cell transplantation for the treatment of hematological malignancies. The incidence of clinically significant GVHD ranges from 10 to 80% and accounts for approximately 10-20% transplant related mortality. The combination calcineurin inhibitor and methotrexate is widely used as a GVHD preventive following myeloablative conditioning; however, there is no standard prophylaxis regimen for Cy/Flu minimal intensity nonablative transplants. The objective of the current study is to compare outcomes in patients treated at a single institution with identical conditioning regimens and supportive methods but different GVHD preventive regimens.
Outcomes on 134 patients who underwent nonmyeloablative transplant between May 2000 and Nov 2011 were retrospectively analyzed. The primary endpoint was incidence and severity of acute GVHD (aGVHD). Secondary endpoints included incidence and severity of chronic GVHD (cGVHD), incidence of relapse, overall survival (OS), progression-free survival (PFS) and causes of death.
Median follow-up was 49 months; the median age at transplant was 56 years, 66% of patient were not in remission at time of transplant (predominately myelodysplasia). Donors were peripheral blood mononuclear cell (PBMC, n=133) or bone marrow (n=1) HLA matched related or partially matched (9/10) donors. GVHD preventive regimens included the following: (1) single agent cyclosporine (CsA); (2) combination CsA/mycophenolate mofetil (MMF); (3) CsA+ basiliximab after ANC > 500/mm3; (4) CsA + basiliximab post-transplant, pre-engraftment; (5) sirolimus + tacrolimus.
The incidence of grade III-IV acute GVHD was lower in patients who received sirolimus/tacrolimus than patients in the cyclosporine group (25% and 32%, respectively; p = .062). There was a significantly higher proportion of patients in the cyclosporine group who had clinical extensive chronic GVHD (62% vs. 25%, p = .008). The incidence of relapse trended higher in the sirolimus/tacrolimus group compared to CsA alone or CsA/MMF (50% vs. 28% vs. 30%, respectively, p= .519). There was a trend towards slightly better OS and PFS with the cyclosporine-based prophylaxis, but follow-up was longer with these regimens.
Sirolimus/tacrolimus provides potent GVHD prophylaxis for nonmyeloablative Cy/Flu allogeneic transplantation; however, may be associated with higher relapse/progression rates. Larger numbers and/or comprehensive analyses of multicenter registry data might help further delineate differences in clinical outcomes between these regimens.
Figure 1 Figure 1.
Figure 2 Figure 2.

Disclosures
No relevant conflicts of interest to declare.
Outcome of Allogeneic Hematopoietic Cell Transplantation in AML or MDS with a HLA-Mismatched Unrelated Donor: A Single Center Analysis
Authors: Schmohl Jörg , Dorn Christiane , Haen Sebastian P. , Faul Christoph , Kanz Lothar , Bethge Wolfgang 
Published: October 2019

Abstract
Introduction: In acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (HCT) can constitute a curative treatment option. Best results are reported using 10/10 HLA-matched donors, and several reports indicated inferior outcomes because of increased graft versus host disease (GVHD) and non-relapse mortality (NRM) if a HLA-mismatched donor is used.
Methods: Here we present a single center analyses evaluating all patients (pts) with AML or MDS receiving allogeneic HCT with a mismatch unrelated donors (MMUD) between 2004 and 2014.
Results:137 pts were evaluated. Median age was 51 years (range 18-76). For myeloablative conditioning (n=52) the following regimens were used: 12 Gy total body irradiation (TBI) and high-dose cyclophosphamide (n=40), or high-dose busulfan and cyclophosphamide (n=8); for reduced intensity conditioning (n=83) fludarabine with either busulfan (n=27), melphalan (n=6), treosulfan (n=7), cyclophosphamide (=15) or TBI (n=19) was used. Stem cell sources were either peripheral blood (n=134) or bone marrow (n=3). The donor/recipient match was a 9/10 alleleic mismatch in 41% and a 9/10 antigen-mismatch in 59% of cases. All but 21 patients received antithymocyte globuline prior to transplantation for GVHD prophylaxis. Post-transplant immunosuppression consisted of a combination of calcineurine inhibitors with either methotrexate (n=65) or mycophenolate mofetil (n=28). Kaplan-Meier estimated overall survival (OS) for all patients at 1 year was 70% and at 3 years 23%. Cumulative incidence of relapse was 32%. Median follow up of patients alive was 40 months (4-122 month). Engraftment with >500 neutrophils and >25.000 platelets was observed at a median of 20 and 20 days after HCT, respectively. Cumulative incidence of NRM until day 100, 1 year and 3 years was 16%, 27% and 28%, respectively. OS and NRM were not different in pts with allelic or antigen-mismatched donors (OS at 1 year/3 years: 65%/48% versus 48%/33% (p=0,2411), NRM at day 100, 1 year and 3 years: 21%, 24% and 33% versus 20%, 27% and 37% (p=0,6210) ). Acute GvHD mostly occurred at lower grades (grade I 34%, grade II 16%, ≥ grade III 10%). Risk of acute GVHD for patients with an antigen-mismatched donor was not different compared to those with an allelic-mismatched donors (51% versus 42%, p=0,4086).
Conclusion: Stem cell treatment with mismatched donors in allogeneic HCT is a valuable and safe option for pts with missing matched stem cell source. Due to optimized pre- and-posttransplant treatment, satisfactory long term survival can be achieved.

Disclosures
No relevant conflicts of interest to declare.
Outcome in Allo- SCT in Patients with Refrectory Acute Lymphoblastic Leukemia with Non TBI Conditioning Regimens
Authors: Sharma Ajay , Nair Velu , Das Sataya Ranjan , Sharma Sanjeevan , Singh Jasjit , Kumar Rajeev , Kotwal Jyoti , Kaur Jasmit 
Published: October 2019

Abstract
Background: Despite intensive remission induction chemotherapy, up to 5–10% AYAs with acute lymphoblastic leukemia (ALL) are primarily refractory.1,2 Of those that achieve a remission, as much as 70–80% fail consolidation largely due to relapse or sustained aplasia. Allogeneic stem-cell transplantation (allo-SCT) remains the only salvage option with curative potentials available, but the long-term benefits of the procedure and whether all patients should benefit from it remains controversial. There has always been a discussion about best conditioning regimen for ALL transplants especially in resource limited situation where TBI is not available. We analyzed our data on allo-transplants for ALL, wherein we had used non-TBI protocols for conditioning.
Study: This study retrospectively analyzes the outcome in 32 patients ( 19 females & 13 males) who underwent Allo-SCT for refractory acute lymphoblastic leukemia at our center between 2000-2013. The median age was 28 years (range, 7–26). 14 patients had relapse, 8 failed re-induction, 5 in partial remission & 7 patients had high risk disease ( Ph+ disease). All patients were in a state of bone marrow remission at the time of transplantation. All received myeloablative conditioning using busulfan( BU) & cyclophosphamide( CY). The stem cell harvesting was done by peripheral G-mobilized stem cell collection from related donors. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. Infection prophylaxis & supportive care was provided as per standard protocols. The median cell dose was 5.4 MNCx10 7/Kg (3.8-7.6) & CD34 cells 3.7x105/Kg. 31 patients engrafted successfully by median day 12(7-23) for White cells & median day 38 ( 27-48) for platelets. One patient experienced late graft failure. 21 patients developed Gd-II acute-GVHD, 11 of them progressed to severe form( Gd-III). 5 pateints had severe grade IV Ac GVHD. 3 of them died chronic-GVHD appeared in 14 patients,. 19 patients (58%%) remain alive after a median of 60 months (range, 6–174); with 13 deaths, mostly from relapse (n=10) and infections (n=3). Overall survival (OS) and progression-free survival (PFS) at 5 years was 53% and 48%, respectively. OS and PFS were significantly better with blasts 20% and time to transplant 1 year.
Conclusions: We conclude that patients with refractory leukemia can benefit from allogeneic BMT, if they are transplanted in a state of remission, by using non-TBI based protocols. Thus in a resource limited situation, the outcome in refractory ALL can still be improved by improvisation of protocols without using TBI in conditioning regimens.

Disclosures
No relevant conflicts of interest to declare.
Analysis of Racial Disparity in Plasma of Healthy Volunteers Using Rotational Thromboelastometry Reveals Higher Prothrombotic Profile in African Americans
Authors: Janbain Maissaa , Liszewski Walter J , Leissinger Cindy A 
Published: October 2019

Racial differences in the incidence of arterial and venous thrombotic events are well established in literature, with a higher incidence noted in African Americans compared to Caucasians. Several studies have tried to explain this difference, by looking separately at chemical biomarkers, socioeconomic and clinical risk factors. Yet the exact reason behind this disparity remains unclear. At least one study of thrombin generation suggested that African ethnicity was associated with increased peak thrombin generation when compared to Caucasians. Rotational thromboelastometry is a visco-elastic methodology that offers a global assessment of hemostasis using either whole blood or plasma. We explored the racial differences in rotational thromboelastometry findings using plasma samples from healthy volunteers.
We studied a cohort of 9 otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 5 African Americans and 4 Caucasians. After informed consent, we collected citrated whole blood samples and processed them within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation of whole blood for 20 minutes, was kept frozen at -70°C, and then thawed at 37°C for 5 minutes prior to testing. Samples were re-calcified with star-tem® reagent, and then the in-tem® reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry parameters including Clot Formation Time, Alpha Angle, and Maximum Clot Firmness were determined. We then compared the data between the two study populations using parametric unpaired Student’s t-test.
Our results showed that the Clot Formation Time was higher in the plasma of Caucasians when compared to African Americans with a difference between means of 40.1 ± 4.4 seconds (p <.0001); the Alpha Angle was lower in Caucasians with a difference between means of 3.45 ± 0.3 degrees (p <.0001); and the Maximum Clot Firmness was lower in Caucasians with a difference between means of 9.75 ± 2 mm (p <.01). These findings demonstrated that the plasma of Caucasians took longer to reach the maximum firmness, and this maximum firmness was less than that reached in the plasma of African Americans. This reveals a significantly increased prothrombotic profile in the plasma of African Americans compared to Caucasians.
Despite the limited number of participants, the striking observed differences in the thromboelastometry parameters suggest that global assays may offer benefit in assessing thrombotic risks in disparate patient populations, as they incorporate multiple components of the hemostatic system. Higher numbers of subjects and assessment of both whole blood and plasma are indicated. We are currently in the process of expanding our cohort to confirm these preliminary results.

Disclosures
No relevant conflicts of interest to declare.
Health Risks Among Adults after a Prolonged Flaring Incident at the British Petroleum Plant in Texas City
Authors: D'Andrea Mark , Mitter Ajay , Reddy G. Kesava 
Published: October 2019

Abstract
Objective: Human exposure to benzene is associated with multiple adverse health effects including hematopoietic malignancies, respiratory irritation, and immune system alterations and central nervous system abnormalities. The purpose of this study is to examine health effects of a benzene exposure among adult subjects from a prolonged flaring incident at the British petroleum (BP) refinery in the Texas City, Texas.
Methods: The study included adults aged 18 years or older who had been exposed and unexposed to benzene. Using medical charts, clinical data including white blood cells (WBC), platelets, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) in adults exposed to benzene were reviewed and analyzed and compared with unexposed adults.
Results: A total of 2213 adult subjects (benzene exposed, n=1826 and unexposed, n=387) were included. Benzene exposed subjects had significantly higher levels of WBC (X 103 per µL) counts (7.9±2.3 versus 6.8±1.6, P=0.0000) and platelet (X 103 per µL) counts (270.8±60.9 versus 242.5±53.7, P=0.0.0000) compared with the unexposed subjects. The mean serum creatinine levels (mg/dL) were also significantly increased in the benzene exposed group compared with the unexposed group (1.0 ±0.2 versus 0.8±0.2, P=0.000). Serum levels of ALP (IU/L) was significantly elevated in the benzene exposed subjects compared with the unexposed subjects (82.1±15.6 versus 71.8±8.2, P=0.000). Similarly, benzene exposed subjects had significantly higher levels of AST and ALT compared with those unexposed to benzene.
Conclusion: Together, the results of the study reveal that Benzene exposure from the prolonged BP flaring incident caused significant alterations in their hematological and liver markers indicating that adult subjects exposed to benzene may be at a higher risk of developing hepatic or blood related disorders.

Disclosures
No relevant conflicts of interest to declare.