Donor Weight Research Articles

Basal CD34+ Cell Count Predicts Peripheral Blood Hematopoietic Progenitor Cells Mobilization in Healthy Donors after Administration of G-CSF

BACKGROUND: Peripheral blood (PB) hematopoietic progenitor cells (HPC) mobilized with G-CSF are the first-choice source for allogeneic stem cell transplantation. We carried out a prospective study on healthy donors (HDs), to identify donor characteristics that could influence the effectiveness of mobilization.STUDY DESIGN AND METHODS: PB-HPC allogeneic donations from sibling HDs were analyzed. We tested somatic variables (sex, age, weight, height, volemia) and blood counts (WBC, platelets, hemoglobin, CD34+ cell count). Two different determinations of CD34+ cells were done in each HD: baseline (before G-CSF administration) and in PB on the morning of the fifth day (after G-CSF administration). HDs received G-CSF subcutaneously at a dose of 10 µg/kg per day.RESULTS: 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. The mean value of CD34+ on day 5 was 90.8 cells/µL, 84.2 cells/µL in females and 97.2 cells/µL in males. The median values of CD34+ on day 5 were 75.5 cells/µL for the overall sample, 74 cells/µL in females and 80 cells/µL in males. On univariate correlation analysis, donor weight r=0.19, P<0.05, height (r=0.20, P<0.05), volemia (r=0.18, P<0.05) and baseline CD34+ (r=0.38, P<0.001) were significant predictors of CD34+ on day 5. Data analysis by gender showed that CD34+ on day 5 were predicted by age (r=-0.30, P<0.05), baseline WBC (r=0.25, P<0.05), baseline CD34+ (r=0.31, P<0.05) in males and by baseline CD34+ (r=0.45, P<0.001) in females. We performed two multivariate analyses either by using ordinary regression (to predict the mean value of CD34+ on day 5) or median regression (to predict the median value of CD34+ on day 5) according to the values of CD34+ at baseline (see table) in the whole study population and separately in females. These results indicate that in the whole study population and by using ordinary regression, a baseline value of CD34+ ranging from 0.5 to 2 cells/µL predicts a mean CD34+ value of 75.7 cells/µL at 5 days whereas a baseline value of CD34+ ≥3 cells/µL predicts a mean CD34+ value of 107.5 cells/µL at 5 days. Furthermore, in the whole study population but by using the median regression, a baseline value of CD34+ ranging from 0.5 to 2 cells/µL predicts a median CD34 + value of 64.6 cells/µL on day 5 whereas a baseline value of CD34+≥3 predicts a median CD34 value of 101.1 cells/µL on day 5.CONCLUSIONS: Baseline, HDs PB CD34+ cell counts correlated with the effectiveness of allogeneic HPC mobilization and could be useful to plan the collection. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Using on-site liver 3-D reconstruction and volumetric calculations in split liver transplantation

Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout© liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g (930-1458 g) for the extended right lobe donors and 312 g (222-396 g) for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts, respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight. On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.

Surgical Complications in En Bloc Renal Transplantation

En bloc pediatric transplantation (EBPT) began with the aim of increasing the donor pool due to the existing high demand for donors. At its inception, it was considered a type of suboptimal transplantation due to its association with a high incidence of vascular, urologic, and immunologic complications. The main objective of this study was to update information on EBPT with the largest case series that exists on a worldwide scale. In a retrospective study, the results obtained from brain-dead donors (BDDs; n = 770) were compared to those of EBPT (n = 100) from January 1990 to December 2012. The median of follow-up was 12.8 years (interquartile range 8.1 to 17.2). The variables collected for analysis were demographic factors (age and sex of recipients, age and weight of donors), renal function, graft survival, recipient survival, surgical complications (thrombosis, lymphocele, urologic complications, and renal artery stenosis and need for revascularization with angioplasty and/or stents). Subsequently in a second analysis, we studied the association between graft survival, thrombosis, angioplasty, stents, and appearance of lymphoceles with the different factors that were considered to be related in accordance with published literature and our own experience. Graft loss due to surgical complications was more frequent in EBPT than in BDD (15% vs 2.2 % in BDD; P < .001), and interstitial fibrosis and tubular atrophy were more frequent in BDD (13% vs 2%; P < .001). EBPT offers a good survival rate after overcoming the possible surgical complications that may arise.

Antiproliferative activity of amino substituted benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles explored by 2D and 3D cell culture system

Benzimidazo[1,2-a]quinolines and benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles with amino chains on the different positions have been evaluated by 2D and 3D assays on the human breast cancer cells. Pentacyclic derivatives were synthesized by microwave assisted amination to study the influence of the thiophene substructure on antitumor activity in comparison to tetracyclic analogues. The results obtained from 2D assay reveals that the antitumor activity is strongly dependent on the nature and position of amino chains. Tetracyclic derivatives displayed selective activity on SK-BR-3 with the 2-amino substituted derivatives as the most active ones while pentacyclic derivatives 6–16 and 21–25 showed more pronounced activity on T-47D. The evaluation of antitumor activity in the 3D assay pointed out that some of the tetracyclic and pentacyclic amino substituted derivatives showed selective activity on the MDA-MB-231 cell line.Influence of physico-chemical properties of the compounds on antiproliferative activity have been investigated by multivariate statistical methods. As a measure of lipophilicity, experimental Chrom LogD values have been determined and number of structural parameters have been calculated for investigated compounds. Main factors contributing to the antiproliferative effect for both 2D and 3D cell cultures are found to be basicity, lipophilicity, molecular weight and number of H-bond donors.

Collection of hematopoietic CD34 stem cells in rhesus macaques using Spectra Optia.

Nonhuman primates, particularly rhesus macaques, are ideal preclinical large animal models to investigate organ tolerance induction protocols using donor hematopoietic stem cells (HSCs) to induce chimerism. Their relatively small size poses some challenges for the safe and effective collection of peripheral blood HSCs through apheresis procedures. We describe our experiences using the Spectra Optia apheresis unit to successfully obtain HSCs from mobilized peripheral blood of rhesus macaques. Mobilization of peripheral blood HSCs was induced using granulocyte stimulating factor (G-CSF) and Mozobil. The Spectra Optia unit was used in 18 apheresis procedures in 13 animals (4.9-10 kg). Animal health was carefully monitored during and after the procedure. Changes in peripheral blood cells before, during and after procedure were determined by complete blood count and flow cytometry. The automatic settings of the Spectra Optia unit were applied successfully to the procedures on the rhesus macaque. All animals tolerated the procedure well with no mortality. Mobilization of HSCs were most consistently achieved using 50 μg/kg of G-CSF for 5 days and a single dose of Mozobil on the 5th day, followed by collection of cells 3 h after Mozobil injection. The final apheresis product contained an average of 23 billion total nucleated cells with 47% granulocytes, 3,871 million total CD3 cells and 77 million CD34 cells which resulted in an average of 10 million CD34+ cells/kg of donor weight. Apheresis of peripheral blood mobilized HSCs in rhesus macaques using Spectra Optia is a safe and effective procedure.

Body Mass Index as Predictor of Vasovagal Reactions in First Time Male Blood Donors

Background: Vasovagal reactions (VVR) are common among blood donors and are known to be inversely associated with donor weight. The relationship between VVR and BMI which adjusts donor weight for height is barely explored. Aim: To study the relationship between VVR and BMI. Method: All whole blood donors in Department of Transfusion medicine, Government Medical College, Thiruvananthapuram over 1 year were included in the study. Female and repeat donors were excluded. The weight and height of donors were collected from their donor registration forms. Donors who had reaction during donation and during post donation refreshment period including minor subjective feeling of uneasiness were tested for association with BMI. Results: BMI was inversely related with VVR, with 11.31% of donors with BMI 30. The mean BMI of donors who had VVR was 22.4 where as donors who did not develop VVR were 22.9. Conclusion: BMI can be a significant predictor of VVR in donors who fulfill the weight criteria for whole blood donation.

Performance and Stability of Polymer Solar Cells Based on the Blends of Poly(3-Hexylthiophene) and Indene-C60 Bis-Adduct**Supported by the Tianjin Natural Science Foundation under Grant Nos 13JCYBJC18900 and 13JCZDJC26700, and the National High Technology Research and Development Program of China under Grant No 2013AA014201.

The performance and morphology stability of polymer bulk heterojunction solar cells based on poly(3-hexylthiophene) (P3HT) as the donor and indene-C60 bisadduct (ICBA) or methanofullerene [6,6]-phenyl C61-butyric acid methyl ester (PCBM) as the acceptor are compared. Effect of the different donor and acceptor weight ratios on photovoltaic performance of the P3HT:ICBA device is studied. The optimal device achieved power conversion efficiency of 5.51% with Jsc of 10.86mA/cm2, Voc of 0.83 V, and fill factor (FF) of 61.1 % under AM 1.5G (100 mW/cm2) simulated solar illumination. However, the stability measurement shows that cells based on P3HT:ICBA are less stable than those of the device based on P3HT:PCBM. Atomic force microscope results reveal that the morphology of the P3HT:ICBA film changed considerably during the storage periods due to unstable interpenetrating D-A network. This observation can be explained by the fact that there is lack of intermolecular hydrogen bonds in the P3HT:ICBA system. However, in the P3HT:PCBM system the molecules in the blend film are firmly held together in the solid state by means of intermolecular hydrogen bonds originating from C-H⃛Os bonds (where Os comes from the singly-bonded O atom of PCBM), forming a stable three-dimensional network. The measured PL decay lifetimes for P3HT:PCBM and P3HT:ICBA systems are 33.66 ns and 35.34 ns, respectively, indicating that the P3HT:ICBA system has a less efficient exciton separation efficiency than that of P3HT:PCBM, which may result in the interfacial photogenerated charges accumulated on the D: A interface. Such progressive phase segregation between P3HT and ICBA eventually leads to the degradation in performance and deteriorates the stability of the device. We also present an approach to enhance the stability of P3HT:ICBA systems by adding PCBM as the second acceptor. Our results show that by carefully tuning the contents of PCBM as the second acceptor, more stable polymer solar cells can be obtained.

Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction.

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.

Systematic N-methylation of oxytocin: Impact on pharmacology and intramolecular hydrogen bonding network

Oxytocin (OT) is a peptide hormone agonist of the OT receptor (OTR) that plays an important role in social behaviors such as pair bonding, maternal bonding and trust. The pharmaceutical development of OT as an oral peptide therapeutic has been hindered historically by its unfavorable physicochemical properties, including molecular weight, polarity and number of hydrogen bond donors, which determines poor cell permeability. Here we describe the first systematic study of single and multiple N-methylations of OT and their effect on physicochemical properties as well as potency at the OT receptor. The agonist EC50 and percent effect for OTR are reported and show that most N-methylations are tolerated but with some loss in potency compared to OT. The effect of N-methylation on exposed polarity is assessed through the EPSA chromatographic method and the results validated against NMR temperature coefficient experiments and the determination of NMR solution structures. We found that backbone methylation of residues not involved in IMHB and removal of the N-terminal amine can significantly reduce the exposed polarity of peptides, and yet retain a significant OTR agonist activity. The results of this study also expose the potential challenge of using the N-methylation strategy for the OT system; while exposed polarity is reduced, in some cases backbone methylation produces a significant conformational change that compromises agonist activity. The data presented provides useful insights on the SAR of OT and suggests future design strategies that can be used to develop more permeable OTR agonists based on the OT framework.

Correlation of Allograft Weight to Recipient Body Weight Index on Renal Function in Kidney Transplantation

BackgroundThe function of renal transplant grafts can be modified by many factors. In one study of graft weight/weight of the recipient, it was concluded to avoid renal transplantation in patients with kidneys with a low ratio between the graft and recipient weight (<2.5 g/kg). ObjectiveThe objective of this study was to describe the association between renal allograft weight and renal function 1 month after renal transplantation in the Mexican population. Material and MethodsWe studied patients who underwent transplantation from living or cadaveric donors with 1 month of follow-up with a functioning graft. An observational, retrospective, analytic study from January 1, 2014 to November 1, 2014 was conducted. Graft weight, donor weight, recipient weight, age, donor gender, recipient creatinine, and renal function were recorded. ResultsA total of 88 patients were included: 35 women (39.8%) and 53 men (60.2%). Sixty (68%) received kidneys from living donors and 28 (31.8%) from deceased donors. Mean recipient body mass index (BMI) was 24.7 (±2.6). Mean graft weight was 152 g (±33.9). Creatinine at 1 month post-transplantation was 1.6 mg/dL (±2.0). Using a linear regression model cold ischemia time was related to serum creatinine at 1 month post-transplantation (P = .020). Using multivariate analysis, significance was observed with respect to these indexes and recipient renal function. Recipient gender also was related and showed statistical significance (P = .015). ConclusionsRenal graft function depends on many factors including the amount of functional renal mass and nephrons required according to the recipient's weight. The donor kidney weigt (DKW) / receptor body weigt (RBW) index should be considered as selection criteria of donors.

Pancreas Transplantation From Very Small Pediatric Donor Using the “Cephalic Placement” Technique: A Case Report

IntroductionThe gap between the number of diabetic patients on the waiting list for transplantation and the number of pancreas donors is growing and it is mandatory to extend criteria for donor eligibility. Several reports showed the feasibility of pancreas transplantation from pediatric donors with comparable outcomes to adult donors in terms of long-term β-cell function. However, there is no consensus about donor age and weight limits. Case ReportWe present two cases of pancreas transplantation alone (PTA) from very small pediatric donors: a 2-year-old female (weight 13 kg, height 88 cm) and a 6-year-old male (weight 29 kg, height 122 cm). We used a novel “cephalic placement” technique. The pancreas was placed upon the aortic carrefour with cephalic pole upward with 3 anchorage points: the left common iliac vein (or the inferior cava vein), the right common iliac artery, and an ileal loop. ResultsNo postoperative thrombosis occurred and the patients gained insulin independence instantaneously. CT scan performed on postoperative day 3 showed regular organ perfusion in both cases. Graft volume and surface calculated by CT reconstruction were, respectively, 25 cc and 89 cm2 in the first case, and 46.5 cc and 123 cm2 in the second case. Postoperative mixed meal tolerance tests showed normal glycemic profile. Patients are actually insulin independent at 4 years and 8 months. ConclusionsPancreases from very young pediatric donors are adequate to restore insulin independence after PTA in adult patients. The “cephalic placement” technique is feasible and effective using very small pancreases.

The impact of donor characteristics on the immune cell composition of second allografts in Chinese people.

The association of the donor characteristics with the immune cell composition in second allografts remains poorly understood. In this study, we investigated retrospectively the effects of the donor characteristics on the immune cell composition in second allografts. The immune cell composition in second allografts of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood harvests from 100 healthy donors (male, 47, female, 53; median age, 39 years old) who underwent a second-time donation were correlated with their donor characteristics. The median counts of CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, CD3(+) CD4(-) CD8(-) T cells and monocytes in allografts were 150·17 × 10(6) /kg, 82·57 × 10(6) /kg, 48·02 × 10(6) /kg and 24·97 × 10(6) /kg, respectively. Multivariate analysis showed that the number of lymphocytes and platelets pre-first collection of G-CSF mobilized blood (FM) was strongly associated with the number of total lymphocytes (for lymphocytes, P = 0·003; for platelets, P = 0·012), CD3(+) T cells (for lymphocytes, P = 0·009; for platelets, P = 0·004) and CD3(+) CD4(+) T cells (for lymphocytes, P = 0·035; for platelets, P = 0·004) in the second allograft. The donor's BMI was negatively related to the number of CD3(+) T cells (P = 0·022) and CD3(+) CD4(+) T cells (P = 0·026) in the second allograft. The donor weight was negatively associated with the number of CD3(+) CD4(-) CD8(-) T cells (P = 0·015) in the second allograft, while the pre-FM white blood cell count showed a positive correlation (P = 0·009). The results demonstrate the impact of the donor characteristics, including pre-FM platelet count and lymphocyte count, donor BMI and weight, on the immune cell composition in the second allograft.

Harvests from bone marrow donors who weigh less than their recipients are associated with a significantly increased probability of a suboptimal harvest yield.

Previous studies have demonstrated the importance of bone marrow (BM) harvest yield in determining transplant outcomes, but little is known regarding donor and procedure variables associated with achievement of an optimal yield. We hypothesized that donor demographics and variables relating to the procedure were likely to impact the yield (total nucleated cells [TNCs]/kg recipient weight) and quality (TNCs/mL) of the harvest. To test our hypothesis, BM harvests of 110 consecutive unrelated donors were evaluated. The relationship between donor or procedure characteristics and the BM harvest yield was examined. The relationship between donor and recipient weight significantly influenced the harvest yield; only 14% of BM harvests from donors who weighed less than their recipient achieved a TNC count of more than 4 × 10(8) /kg compared to 56% of harvests from donors heavier than their recipient (p = 0.001). Higher-volume harvests were significantly less likely to achieve an optimal yield than lower-volume harvests (32% vs. 78%; p = 0.007), and higher-volume harvests contained significantly fewer TNCs/mL, indicating peripheral blood contamination. BM harvest quality also varied significantly between collection centers adding to recent concerns regarding maintenance of BM harvest expertise within the transplant community. Since the relationship between donor and recipient weight has a critical influence yield, we recommend prioritizing this secondary donor characteristic when selecting from multiple well-matched donors. Given the declining number of requests for BM harvests, it is crucial that systems are developed to train operators and ensure expertise in this procedure is retained.

Abstract P1-03-02: Estrogens contribute to cytokine upregulation and cancer stem cell recruitment upon breast cancer contact with mature human mammary adipocytes: Effects of estrogen type and adipocyte donor weight

Abstract Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. While obesity confers increased cancer risk and worse outcome, mechanisms thereof are not fully known. We show prolonged co-culture of fat cells (human adipocyte stem cells, differentiated adipocytes or mature adipocytes) from breast tissue together with breast cancer lines or cultured primary dissociated human breast tumor cells increases secretion of six different pro-inflammatory cytokines, each of which contributes to tumor progression through cancer stem cell recruitment. Prolonged exposure to fat cells or to each cytokine increases the proportion of cells that form mammosphere and express ALDH1 activity in vitro and that can initiate primary orthotopic tumors and metastasis in vivo. Adipocyte and cytokine exposures activate Src, and Src family kinase activity leads to induction of embryonic transcription factors that upregulate miR302b. miR302b induction is Sox2-dependent, promotes cytokine-driven sphere formation, and in turn, stimulates cMYC and SOX2 expression. Src is not only activated by adipocyte or cytokine exposures, it is also required to sustain cytokine induction, since Src inhibitors decrease cytokine production after co-culture. Cytokine upregulation was much greater after co-culture of ER+ breast cancer cells with mature, aromatase positive, adipocytes than with adipocyte stem cells. Cytokine induction was estrogen regulated. The mechanisms of cytokine induction, ER-coactivation and effects of different estrogenic ligands will be presented. Present data illuminate the increased risk of breast cancer after menopause, particularly in obese women and the increased breast cancer mortality with obesity: cancer cell invasion into local fat, in the presence of high local aromatase and intracellular estrogen would establish feed-forward loops to activate Src, maintain pro-inflammatory cytokine production and increase tumor initiating cell abundance, tumor growth and metastasis. These data link obesity related pro-inflammatory cytokines to Src activation and cancer initiating cell abundance, and provide a novel rationale for Src inhibitors together with endocrine therapy for breast cancer. Citation Format: Slingerland J, Picon-Ruiz M, Jang K, Morata-Tarifa C, Pan C, Besser A, Kim M, Ince TA, Howard GA, El-Ashry D. Estrogens contribute to cytokine upregulation and cancer stem cell recruitment upon breast cancer contact with mature human mammary adipocytes: Effects of estrogen type and adipocyte donor weight. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-03-02.

Single vs dual (en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience.

To compare outcomes between single and dual en bloc (EB) kidney transplants (KT) from small pediatric donors. Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached to the inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients. From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors (17 mo vs 38 mo, P < 0.001), mean weight (11.0 kg vs 17.4 kg, P = 0.046) and male donors (50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time (21 h), kidney donor profile index (KDPI; 73% vs 62%) and levels of serum creatinine (SCr, 0.37 mg/dL vs 0.49 mg/dL, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence (12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay (mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection (6% vs 16%), operative complications (3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively (all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/dL vs 1.35 mg/dL and 72.5 mL/min per 1.73 m(2) vs 60.5 mL/min per 1.73 m(2) (both P = NS) in the dual EB and single KT groups, respectively. By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.

Donor to recipient sizing in thoracic organ transplantation.

Donor-to-recipient organ size matching is a critical aspect of thoracic transplantation. In the United States potential recipients for lung transplant and heart transplant are listed with limitations on donor height and weight ranges, respectively. Height is used as a surrogate for lung size and weight is used as a surrogate for heart size. While these measures are important predictors of organ size, they are crude surrogates that fail to incorporate the influence of sex on organ size. Independent of other measures, a man's thoracic organs are approximately 20% larger than a woman's. Lung size can be better estimated using the predicted total lung capacity, which is derived from regression equations correcting for height, sex and age. Similarly, heart size can be better estimated using the predicted heart mass, which adjusts for sex, age, height, and weight. These refined organ sizing measures perform better than current sizing practice for the prediction of outcomes after transplantation, and largely explain the outcome differences observed after sex-mismatch transplantation. An undersized allograft is associated with worse outcomes. In this review we examine current data pertaining to size-matching in thoracic transplantation. We advocate for a change in the thoracic allocation mechanism from a height-or-weight-based strategy to a size-matching process that utilizes refined estimates of organ size. We believe that a size-matching approach based on refined estimates of organ size would optimize outcomes in thoracic transplantation without restricting or precluding patients from thoracic transplantation.

English

Background: Platelet utilization has increased much more than other components worldwide in last 2 decades. Single donor platelets (SDP) have several benefits over random donor platelets, therefore being preferred. However, stringent criteria of donor selection and therefore high rate of deferral are major limitations to availability of SDP. Aim: The present study was carried out to evaluate the various reasons for deferrals in plateletpheresis donors. Material & Methods: This retrospective study was conducted to analyze the reasons for deferrals in platelet donors at Blood bank, SMSR Weight-55 Kg; Good vein in one or both arms; no Aspirin intake in last 72 hours & minimum interval of 72 hours from last plateletpheresis along with all other criteria for whole blood donation. Results: Out of 283 donors screened, 58 were deferred with an overall deferral rate of 20.5%. Out of these, 89.65% deferrals were due to temporary causes. Low platelet count & low hemoglobin levels accounted for 44.82% & 18.96% temporary deferrals respectively. 10.34% of deferred donors had Hb in range of 11.5-12.4gm% while 8.6% deferred donors had platelet count of 1.4 lacs to 1.49 lacs and 6.8% had weight in range of 50-55 kg. Conclusion: As it is difficult to convince donors for plateletpheresis, screening criteria of the same should be revised and formulated separately from whole blood donation. Criteria for hemoglobin and donor weight for plateletpheresis can be relaxed.

Pediatric En Bloc Kidney Transplants: Clinical and Immediate Postoperative US Factors Associated with Vascular Thrombosis.

Purpose To evaluate clinical and immediate postoperative ultrasonographic (US) risk factors associated with vascular thrombosis of pediatric en bloc kidney grafts. Materials and Methods This institutional review board-approved HIPAA-compliant retrospective study consisted of 195 recipients of pediatric en bloc kidney grafts throughout a 10-year period. The average recipient and donor age was 45 years (range, 7-74 years) and 9 months (range, 0-84 months), respectively. Clinical factors and immediate postoperative US findings were assessed. Categorical variables were evaluated by using the Fisher exact test and linear models with generalized estimating equations. Results Seventeen patients (23 kidneys) experienced thrombotic events. In six patients (eight kidneys), thrombosis occurred intraoperatively. The remaining 11 patients (15 kidneys) received a diagnosis of thrombosis on postoperative days 1-13. Recipients more than 40 years old had a higher incidence of arterial thrombosis than did younger recipients (eight of 62 vs three of 133, respectively; P < .01). Recipients were more likely to develop thrombosis with donor weight less than 5 kg (10 of 52 vs seven of 140 with donor weight of ≥ 5 kg; P < .01), with intraoperative perfusional concern (10 of 21 vs seven of 174 without; P < .01), or with right-sided allograft placement (10 of 64 vs seven of 131 left sided; P = .03). At US of the 15 postoperative thrombotic events, the incidence of thrombosis was greater when donor arterial velocity was less than 100 cm/sec (seven of 56 vs four of 126 with velocity ≥ 100 cm/sec; P = .04). An intrarenal arterial resistive index of less than 0.6 was associated with higher incidence of arterial thrombosis (nine of 123 vs zero of 217, respectively; P = .01). A resistive index greater than 0.8 was associated with a higher incidence of venous thrombosis (four of 13 vs one of 217, respectively; P = .04). Conclusion Clinical factors and immediate US findings can help stratify patients receiving pediatric en bloc kidneys into risk categories for vascular thrombosis that, if proven in prospective studies, could affect immediate postoperative treatment. (©) RSNA, 2015.

Potent Stem Cell Mobilization with the Novel CXCR4 Antagonist POL6326 - Results of a Phase IIa Dose Escalation Study in Comparison to G-CSF

Background:Stem cell mobilization (SCM) with G-CSF is efficient but - although overall safe - inconvenient because of the five-day injection regime and certain contraindications. Side effects, sometimes severe, are frequent. These disadvantages fuel the quest for alternative mobilizing agents. Mobilization with the CXCR4-inhibitor plerixafor is rapid, albeit insufficiently efficacious on its own. POL6326, a potent 2nd generation macrocycle CXCR4 antagonist, has demonstrated rapid mobilization kinetics and efficacy in mice. We herein report the results of a Phase IIa dose escalation trial where SCM in response to POL6326 was compared with G-CSF in healthy volunteer stem cell donors.Methods:In this Phase IIa open label trial, healthy volunteer stem cell donors with average mobilization (121±7 CD34+ cells/μL, MW±SEM)after a five-day course of G-CSF, and a wash-out period of at least 6 weeks, received POL6326 at 500-2500 µg/kg as a single 2-hour i.v. infusion. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in 3-10 subjects/dose group. Subgroups received two doses of POL6326, 1000 and 2500 µg/kg or 1500 and 2500 µg/kg, at least 2 weeks apart (paired intra-individual analysis). For PK and PD blood samples were collected before (0) and at 2, 3, 4, 6, 8 and 24 hrs after infusion start. Complete blood count, CD34+, CFU-C count and PK were assessed at all time points. At 0, 4, 8 and 24 hrs extensive phenotyping of mobilized mature and immature leukocyte subsets was performed. Eight to 14 days after treatment volunteers underwent extensive clinical and laboratory follow-up.Results:POL6326 was very well tolerated. Several volunteers experienced a mild urticarial or itchy macular rash which responded well to H1/H2 blockade. Rating of tolerability/adverse events by volunteers (questionnaire) compared favourably with G-CSF administration. Exposure (Cmax, AUC) was dose-linear. At all doses tested POL6326 mobilized CD34+ progenitor cells and colony-forming cells (CFU-C, Figure 1) exceeding reported peak mobilization with plerixafor in donors at all except the lowest dose levels. In this dataset mobilization after doses of 2000 or 2500 µg/kg did not appear meaningfully stronger than after 1500 µg/kg. The SCM response for CD34+ cells to doses ≥1500 µg/kg was 36.9±2.4/µL (mean±SEM), or 1/3 that of G-CSF (y=0.324x). Good SCM with G-CSF was predictive of good SCM with POL6326 (r=0.63). One/5.7 POL6326-mobilized CD34+ cells was clonogenic (G-CSF: 1 CFU-C/3.4 CD34+ cells) possibly indicating a more immature phenotype of CD34+ cells mobilized by POL6326. POL6326 caused mixed leucocytosis with peak values in the mid-20K/µL. B-lymphocytosis was more and neutrophilia and monocytosis were less pronounced after POL6326 than G-CSF. Compared to G-CSF the subset of plasmocytoid dendritic cell progenitors (pDC) was enriched to a distinct population within the CD34+ cells following SCM with POL6326 as previously described for plerixafor. At the 24 h time point, blood values were well on their way towards normal, and at follow-up all laboratory values had normalized.Summary/Conclusions:The novel CXCR4-antagonist POL6326 is safe, well tolerated, and provides efficient mobilization of HSPCs. Based on the number of mobilized CD34+ cells at higher doses in this study, we conclude that a standard dose of 4x10E6 CD34+ cells/kg can be extracted with a single apheresis for most recipients unless their body weight significantly exceeds the donor weight. However, exploration of alternative dosing regimens may provide even higher mobilization responses. POL6326 can be an effective mobilizing agent for allogeneic donors, including subjects with contra-indications to G-CSF. [Display omitted] [Display omitted] DisclosuresEscot:Polyphor Ltd.: Employment. Douglas:Polyphor Ltd.: Employment. Romagnoli:Polyphor Ltd.: Employment. Chevalier:Polyphor Ltd.: Employment. Dembowsky:Polyphor Ltd.: Consultancy. Hooftman:Polyphor Ltd.: Employment. Bonig:Polyphor Ltd.: Research Funding.