Donor Gender Research Articles

Donor Kidney Adapts to Body Dimensions of Recipient: No Influence of Donor Gender on Renal Function After Transplantation

Female kidneys and kidneys from small donors have been suggested to perform worse after kidney transplantation. Here, we evaluate the impact of gender and body dimensions on posttransplantation GFR in living donor transplantation. Two hundred and ninety-three donor-recipient pairs, who were transplanted at our center were evaluated. All pairs had detailed renal function measurement ((125) I-iothalamate and (131) I-hippuran) 4 months predonation in the donor and 2.5 months posttransplantation in donor and recipient. For 88 pairs, 5 years of recipient follow-up was available. Delta GFR was calculated as (recipient GFR-donor single kidney GFR). Recipients of both male and female kidneys had similar renal function at early and long term after transplantation. Male recipients had higher ERPF, ΔGFR and ΔERPF at both time points. Kidneys of donors smaller than their recipient had higher ΔGFR and ΔERPF than kidneys of larger donors at both time points (p < 0.05). In multivariate analysis, ΔGFR was predicted by donor/recipient BSA-ratio together with transplantation related factors (R(2) 0.19), irrespective of donor and recipient gender. In conclusion, in living donor transplantation, female kidneys perform as well as male donor kidneys. Kidneys adapt to the recipient's body size and demands, independent of gender, without detrimental effects in renal function and outcome up to mid-long term.

Impact of recipients’ socio-economic status on patient and graft survival after liver transplantation: The IsMeTT experience

Aim We aimed to determine whether education level and socioeconomic status in a cohort of liver transplant recipients in the south of Italy were potential predictors of graft and patient survival. Methods This retrospective study included 221 liver transplant recipients at Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione between January 2006 and September 2009. Donor gender and age, cold ischaemic time, extended criteria donors, recipient age, gender, body mass index, primary aetiology, Model for End-Stage Liver Disease score, co-morbidities, patient health score assessed on the basis of clinical follow-up, highest level of education achieved, and socioeconomic status were collected and analysed. Results Kaplan–Meier analysis of survival measured by education level and socioeconomic status showed a higher survival rate in patients with higher education level ( p = 0.04) and socioeconomic status ( p = 0.01). After adjusting for all covariables, results of the multivariate Cox regression analyses showed that only socioeconomic status remained an independent and significant predictor of overall survival (Hazard Ratio = 0.16, p = 0.03). Conclusion Patient survival after liver transplantation was influenced by low income, low educational level, and lack of access to quality health care. Prospective clinical studies are necessary to fully identify the impact of socioeconomic status on long-term health outcomes, and to propose an evidence-based guide to clinical intervention.

Fresh frozen plasma quality: relation to age and gender of blood donors

In view of demographic changes, it is becoming increasingly necessary to make allowance for the fact that older individuals in good health are generally more willing to donate blood and hence they should be allowed to do so irrespective of an upper age limit. In this respect, evidence has to be produced that there is neither an age-related increase in risks to the donor nor any influence on the safety and efficacy of the blood components. It was therefore of interest to examine the quality of therapeutic plasma in relation to a donor's age and also a donor's gender in view of the preferred use of male donor plasma for reducing the risk of transfusion related acute lung injury. Citrate-phosphate-dextrose (CPD) units of whole blood taken in each case from 50 blood donors (30 men and 20 women) of three age groups (cohort 1 = 69-71 years, cohort 2 = 66-68 years and cohort 3 = 50-52 years) were filtered, centrifuged and then separated into the relevant blood components. The plasma samples were assessed for international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, factor V (FV), factor VIII (FVIII), antithrombin (AT), protein S and plasminogen. While aPTT showed only slight age-related differences of no significance, the INR levels of cohort 1 were significantly higher than those of cohorts 2 and 3. However, in terms of gender, this applied to male donors only. The differences in INR are demonstrated by lower FV levels of male cohort 1 donors, although this is not statistically significant in comparison with the other two age groups and with female donors. Female donors of all cohorts, however, exhibited noticeably lower aPTT levels than male donors. Lower INR and aPTT values in women could be a sign of a lower dilution affected by CPD anticoagulant as compared to male plasma. An increase in FVIII levels was also apparent with increasing age (P < 0·05), particularly in male donor plasma. The fibrinogen levels suggest a slight, though insignificant, age-related increase and no significant gender-dependent effect. The plasma levels of AT and plasminogen were unremarkable. The plasma of female cohort 3 donors exhibited a protein S concentration that was slightly lower by comparison. Compared with the other two cohorts, cohort 1 plasma levels were similarly above or below the normal range derived from cohort 3 (central 95% range) for all parameters tested. International Normalized Ratio, aPTT, FVIII, FV, fibrinogen and protein S, as quality indicators for the efficacy of therapeutic plasma, revealed a moderate correlation with age and gender. Compared with the usual reference ranges, the differences were not significant enough to identify any relevant imbalance between procoagulating, anticoagulating and fibrinolytic factors that might influence product quality where the increasing age of the donors or the preference of male donor plasma was concerned.

Delayed Graft Function After Renal Transplantation: An Unresolved Problem

Unlike other areas in renal transplantation, delayed graft function (DGF) remains an apparently unavoidable complication owing to the characteristics of current donors. The aim of this study was to analyze risk factors for DGF in relation to graft and patient survivals. We retrospectively analyzed 507 renal transplant recipients with a median follow-up of 74.83 ± 45.06 months. DGF, which occurred among 189 patients (36.8%) was defined as requirement for dialysis within the first week after transplantation. Donor (P = .000) and recipient (P = .000) age were greater in the DGF group without differences in recipient or donor gender, HLA sensitization, or dialysis time before transplantation. Donor factors as the cause of death associated with DGF were secondary cerebrovacular stroke (P = .002) and hypertensive history (P = .000). Recipient characteristics associated therewith were higher body mass index (P = .000), smoking habit (P = .003), ischemic cardiopathy (P = .01), and dyslipidemia (P = .05). Moreover, the DGF group showed longer cold ischemia (P = .01) and vascular anastomosis (P = .02) times. On multivariate analysis, recipient age (P = .00) and smoking habit (P = .01) together with a donor history of hypertension (P = .02) were independent risk factors for DGF. No differences were observed in acute rejection incidence (P = .07) with worse renal function during follow-up (P < .05). Graft (81% vs 88%; P = .00) and patient (89% vs 95%; P = .00) survivals at 5 years were lower among the DGF group. In conclusion, DGF which was associated with factors related to the donor, the recipient, and the surgical times, produced worse graft and patient survivals. Shortening the cold ischemia time seems to be a modifiable variable to reduce DGF.

Interstitial Fibrosis Evolution on Early Sequential Screening Renal Allograft Biopsies Using Quantitative Image Analysis

Screening renal biopsies (RB) may assess early changes of interstitial fibrosis (IF) after transplantation. The aim of this study was to quantify IF by automatic color image analysis on sequential RB. We analyzed RB performed at day (D) 0, month (M) 3 and M12 from 140 renal transplant recipients with a program of color segmentation imaging. The mean IF score was 19 ± 9% at D0, 27 ± 11% at M3 and 32 ± 11% at M12 with a 8% progression during the first 3 months and 5% between M3 and M12. IF at M3 was correlated with estimated glomerular rate (eGFR) at M3, 12 and 24 (p < 0.02) and IF at M12 with eGFR at M12 and 48 (p < 0.05). Furthermore, IF evolution between D0 and M3 (ΔIFM3-D0) was correlated with eGFR at M24, 36 and 48 (p < 0.03). IF at M12 was significantly associated with male donor gender and tacrolimus dose (p = 0.03). ΔIFM3-D0 was significantly associated with male donor gender, acute rejection episodes (p = 0.04) and diabetes mellitus (p = 0.02). Thus, significant IF is already present before transplantation. IF evolution is more important during the first 3 months and has some predictive ability for change in GFR. Intervention to decrease IF should be applied early, i.e. before 3 months, after transplantation.

Trends in Renal Transplantation in Patients With Human Immunodeficiency Virus Infection: An Analysis of the United States Renal Data System

We examined the United States Renal Data System registry to analyze trends in renal transplantation in patients with human immunodeficiency virus (HIV) infection. A retrospective cohort study was performed using the United States Renal Data System, analyzing patients receiving renal transplants from January 1, 1995, to September 29, 2006. Factors independently associated with transplantation in HIV-infected patients with end-stage renal disease were identified. There was a significant increase in renal transplant recipients who were HIV seropositive who received renal transplants from 2001 to 2006 (n=208, 0.26%) versus 1995 to 2000 era (n=43, 0.06%, P<0.001). Before 2001, only 18 states performed renal transplants in HIV-infected patients, whereas most states transplanted HIV-infected patients in the second era. There were more African American recipients with HIV infection from 2001 to 2006 compared with the earlier cohort (n=118 vs. 8, P<0.001). Patients with HIV infection were more likely to have received induction therapy (n=121 vs. 37, P<0.001) and tacrolimus maintenance suppression (n=105 vs. 13, P<0.001) in the latter era. There were also more deceased donor transplants from 2001 to 2006 (n=143 vs. 25, P<0.001). In logistic regression analysis, when adjusted for multiple factors including recipient and donor age, race, gender, and donor type, patients with HIV infection were more likely to have been transplanted after 2001 (adjusted odds ratio, 2.21; 95% confidence interval=1.49-3.28). In analysis adjusted for multiple factors including hepatitis C virus coinfection, HIV infection was not significantly associated with all-cause graft loss. There has been a dramatic increase in the number of transplants among HIV-infected patients. These findings suggest improved access to transplant wait listing and better management of immunosuppression, especially among African American patients.

Donor–recipient gender difference affects severity of dry eye after hematopoietic stem cell transplantation

To determine whether the incidence rate and severity of dry eye after hematopoietic stem cell transplantation varies with donor vs recipient gender. We limited this study to patients received bone marrow transplantation (BMT). In all, 172 patients received BMT at Keio University School of Medicine between January 2000 and May 2007. Of them, 136 recipients who survived at least 70 days were studied prospectively. We classified the 136 patients according to the gender of the donor and the recipient (group I: female to female; group II: male to male; group III: male to female; group IV: female to male). The incidence and severity of chronic graft-vs-host disease-associated dry eye were determined for each group. The donor gender was masked when we assessed dry eye and calculate the incidence. The incidence of dry eye was 47.4% for group I, 37.5% for group II, 58.6% for group III, and 42.9% for group IV. The percentage of patients with severe dry eye was 44.4, 50.0, 35.3, and 77.8% respectively. There was a significant difference between the percent severe dry eye/total dry eye incidences in groups III and IV (P=0.0375) (odds ratio, 7.6; 95% confidence interval, 1.00-101.01). Close attention must be paid to the development of dry eye in cases of female to male BMTs, because the ratio of severe/total dry eye is more common in cases of female to male BMTs than in other gender combination.

Donor and Recipient Gender Distribution in a Saudi Kidney Transplant Center

Worldwide reports from national renal registries show a donor gender imbalance in living renal transplantation. In these studies women represent on the one hand about 65% of living donors and on the other hand, receive fewer kidneys than men. Because of scarcity of reports on this matter from the Eastern world, we undertook this study to assess the gender demographics of recipients and living donors in our transplant center in the eastern region of Saudi Arabia. We retrospectively reviewed our living related transplantations performed from 1992 to 2008 ( n = 135). Ninety-one males (67.4%) versus 44 females (32.6%) donated a kidney ( P = .0000.) The male predominance ( n = 80; 59.3%) was also noticed among recipients with 80 versus 55 females (40.7%; P = .001). When splitting the results into two periods, 1992 to 1999 versus 2000 to 2008, we noticed a trend to an improved donation rate from females, rising from 29% to 38.7% ( P = NS). Further analysis showed that brothers were giving more frequently to brothers than to sisters (38 vs 11; P < .001) and that sisters donated equally to brothers and sisters (12 vs 11; P = NS). Interspousal donation showed no significant difference between husband to wife and vice versa (4 vs 5). Unlike the international experience, our study showed men to be donating more kidneys than women. Sociocultural reasons may have a role in such findings.

Gender and living donor kidney transplantation

Renal transplantation is the first choice of treatment for end-stage renal disease (ESRD) patients. It offers a longer life span, a better quality of life, and lower health care costs as compared to long-term dialysis. In the past years, a constantly rising demand of kidneys on the one hand and a shortage of disposable organs on the other hand pose a growing challenge on transplant medicine. Donor and recipient gender may influence many aspects of kidney transplantation, but the nature of these interactions is still unclear. This article summarizes a part of our present knowledge in the field of gender-related kidney donation and kidney transplantation. Causes for gender disparity and its consequences will be discussed.

Bioelements and mineral matter in human livers from the highly industrialized region of the Upper Silesia Coal Basin (Poland)

Contents of mineral substance, silica, and a range of bioelements and toxic elements (Mg, Na, K, Ca, Ba, Zn, Cr, P Al, Cd, Mn Cu, Ni, Pb, Sr, Fe) in 38 livers of donors from the Upper Silesia Coal Basin (southern Poland) are presented. Elements were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) with the exception of silica that was estimated colorimetrically. Concentrations, concentration variability, and correlations between selected liver components determined for the total population are related to donor age, gender, and lesion occurrence. Correlations between particular elements were found using correlation coefficient values and the Fisher transformation. Mineral substance in the livers lies in the range 0.40-5.03wt%. With increasing donor age, mineral-matter content decreases to a minimum for the 40-60years of age range. Microbioelement contents show a similar tendency, while microbioelements and toxic elements reach maximum contents in donors aged 60-80years. All elements show content decreases in livers from the oldest group (>80years). Silica contents increase with age. Variability of element contents is lowest in the older subpopulations. Livers with lesions show lower element contents and variability. The results are compared to literature data for regions of Poland assumed to be of low pollution and to data from comparable regions in Japan and Hungary. Up to our knowledge, this paper is the first work describing the total contents, as distinct from contents of selected elements, of mineral substance in human livers.

Influence of Donor and Recipient Gender as well as Selected Factors on the Five-Year Survival of Kidney Graft

The aim of the study was to determine the impact of the gender of renal allograft donor and recipient on the graft function over a 5-year follow-up period. The 154 kidney grafts from 77 donors transplanted into recipients of both genders. Two study groups were formed: one group consisted of male donors, while the other consisted of female donors. The recipients in each of the groups consisted of a pair, one male and one female. 71% of grafts survived the five-year period in the group of male and female recipients when the donor was male; in case of female donors, the rate was 62.5%. Depending on the gender of the donor and the recipient, the rates of grafts with five-year survival were as follows: 79.2% for male donors and female recipients (MF); 62.5% for male donors and male recipients (MM). The difference between both groups was not statistically significant. In the case of female donors and male recipients (FM), the five-year survival rate was 58.3%, while in female donors and female recipients, the five-year survival rate was 64.1%. Grafts from male donors show a trend towards better five-year survival compared to grafts from female donors. The highest five-year survival rate was observed when the donor was male and the recipient was female; the lowest rate was observed for female donors and male recipients.

Prevalence Of Antibodies To Hepatitis C Virus In Blood Donors In Nnewi, South-Eastern Nigeria; In Association With Blood Groups

Background: In spite of the fact that Hepatitis C virus (HCV) infection is a risk factor for hepatocellular carcinoma (HCC), nonHodgkin’s lymphoma (NHL) and renal cell carcinoma (RCC); testing for antibodies to HCV is not yet mandatory in Nnewi, and most other centres in Nigeria. This work was done to determine the prevalence of antibodies to HCV among blood donors and assess if there is any association with the donor blood group, sex and age.Materials and methods: Data from 1229 blood donors who presented to the blood bank of the Nnamdi Azikwe University Teaching Hospital between 2005 and 2009 were retrospectively studied. Donor blood was tested for antibody to HCV using rapid immunoassay that quantitatively detects this antibody using recombinant HCV antigen. ABO and Rhesus blood groups were determined using monoclonal antibodies according to standard protocol.Result: The prevalence of HCV antibodies was found to be 2.0%. The age group 21-30 years was found to be the lowest risk group (1.4% seroprevalence). Seroprevalence increased after the age of 30 years, though not linearly, with the highest rate (3.2%) recorded in the 31-40 years and 51-70 years age groupsAmong the blood groups, O Rh D positive had the highest number of donors and a seroprevalence of 2.4%; compared to A Rh D positive (1.3%), A Rh D negative (9.1%), and O Rh D negative (9.1%). Other blood groups did not have any case of HCV seropositivity. No significant correlation was found between HCV antibody status and blood group, age or gender. Gender however was found to be significantly correlated with age (p<.05)Conclusion: The Prevalence of HCV antibodies in blood donors in Nnewi, Nigeria is moderate; age and gender of donors seem to be important factors affecting it. Screening of all blood donors should be made mandatory in order to prevent the transfer of hepatitis C infection by blood transfusion.

Utilization of Elderly Kidney Donors (>70 Years) Does Not Affect Graft Survival in the Medium Term

Background The need for organs for renal transplantation has encouraged the use of grafts from increasingly older donors. Earlier studies performed in Spain have shown the suitability of donors aged 60–65 years. In this single-center study, we evaluated our results using donors >70 years old. Methods We evaluated 401 primary transplantations performed from January 2000 to December 2009. Their initial immunosuppression was a tacrolimus-based ( n = 324), cyclosporine-based ( n = 70) or calcineurin inhibitor–free ( n = 7) regimen patients. Recipients were classified according to the donors age: <50 (42.6%); 50–70 (39.7%) and >70 (17.5%) years. Results There were no differences in recipient or donor gender, time on dialysis, cold ischemia, delayed graft function, or acute rejection episodes. However, the mean age was higher among patients who received grafts from donors >70 years old; 42.5 ± 12.4 years for <50, 58.1 ± 8.2 years for 50–70, and 65.7 ± 7.2 years for >70; ( P = .000). The serum creatinine at 12 months was increased according to the age of the donor; 1.4 ± 0.6, 1.8 ± 0.6, 70 and 1.7 ± 0.5 mg/dL, respectively ( P = .001). The graft survival rates at 5 years were 81%, 74%, and 70%, respectively ( P = .519). Upon multivariate analysis only HLA-DR mismatches, delayed graft function, and acute rejection episodes were associated with graft loss. Patient survival rates (86%) at 5 years were similar among recipients from donors aged 50–70 and >70 years, but higher (96%) for those who received a graft from a donor <50 years ( P = .003). Conclusions Nearly 20% of donors were >70 years old in our study. Their kidneys displayed excellent short-term outcomes.

Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients

Tolerance has been defined as stable graft function off IMS. We reviewed the data of 369 pediatric liver transplant patients to examine demographic differences that may have a PV of pediatric LT tolerance. Of the 369 patients, 280 patients were stable with detectable blood levels of IMS agents and with good graft function without biopsy proven REJ > 1 yr posttransplantation, 18 patients were noted to be TOL off IMS, 27 patients were taking MIS with drug levels below detectable range by standard laboratory parameters, and 44 patients developed one or more episodes of biopsy proven acute or chronic REJ > 1 yr post-transplantation. Variables, including percentage of biliary atresia, type of transplanted organ, history of EBV infection, patient and donor gender, and ABO blood type mismatch between recipient and donor did not have PV of tolerance. Average age in years was 1.37 ± 1.53 (0.3-4.9) for TOL, 1.14 ± 0.89 (0.4-3.1) for MIS and 3.35 ± 4.45 (0.3-16) for REJ. Age difference of TOL/MIS vs. REJ was significant (p =0.002) and TOL vs. REJ was significant (0.01). Age at the time of transplantation is an important predictor in the development of pediatric LT tolerance.

Analysis of Donor Demographic and Laboratory Parameters Affecting CD34+ Cell Mobilization In Healthy Allogeneic Pediatric Peripheral Blood Stem Cell (PBSC) Donors

AbstractAbstract 2259 Background:In healthy adult donors undergoing blood stem cell mobilization, we previously showed that the single strongest factor related to peak pre-apheresis circulating CD34+ cell counts was the total dose of granulocyte colony-stimulating factor (G-CSF) administered to the donor. Donor weight and gender were also highly correlated with peak CD34+ cell mobilization, to the degree that they contributed to the total dose of G-CSF administered. To determine if this relationship applied to younger donors, we analyzed the factors affecting PBSC mobilization in healthy allogeneic pediatric subjects. Methods:A retrospective analysis of 44 consecutive allogeneic PBSC collections performed between 1998 and 2009 in healthy pediatric donors in a single institution was done. Pediatric subjects were defined as less than 18 years old and less than 60 kg. Mobilization was with G-CSF (filgrastim) alone, given subcutaneously as 10 mcg/kg once daily (n=42), or 8 mcg/kg BID (n=2), for 5 consecutive days. Leukapheresis was initiated on day 5, at least 2 hours after the final G-CSF dose, using either the CS3000 (Fenwal) or Spectra (Gambro) cell separator. Central venous access was necessary in 29 of 44 subjects (66%). Donor demographics, self-reported ethnic backgrounds, and peripheral blood and component CD34+ cell counts were assessed at each procedure. All subjects were healthy siblings of patients undergoing hematopoietic transplantation for hematologic malignances, marrow failure syndromes, solid tumors, and congenital immune deficiencies. Donors gave assent/consent for participation in IRB-approved institutional protocols. Results:Donor age ranged from 3.8 to 17.8 years (mean 11.5 years), with 10 subjects (23%) under the age of 6 years, 15 (34%) between 7 and 12 years, and 19 (43%) between 12 and 17 years. Donor weight ranged from 16.1 to 59.1 kg (mean 38.6 kg). The cohort self-reported their ethnicity as 18 (41%) individuals being Hispanic, 16 (36%) Caucasian, 6 (13%) Black, and 3 (7%) Asian; 28 of 44 (63%) were female. G-CSF dose ranged from 7.6 to 16.7 mcg/kg, with 37 (84%) of the subjects receiving 9 to 13 mcg/kg (mean 10.2), and 6 (14%) receiving greater than 14 mcg/kg. Peak CD34+ count, assayed on a sample collected immediately prior to starting apheresis, was 75 ± 36 per mL (range 25 to 205/mL). A mean of 29.6 × 106 CD34+ cells (range 8.7 to 71.0) were harvested per liter processed, with 13.0 ± 5.4 liters processed per procedure (range 6.0 to 25.5 liters). In this manner, a total of 358 × 106 CD34+ cells (range 120–952 × 106) were collected per procedure, yielding a mean of 9.5 ×106 cells/kg recipient weight (range 3.17 to 20.8 ×106 cells/kg). Average procedural CD34+ collection efficiency was 57%. In univariate regression analysis, peak peripheral blood CD34+ counts on day 5 of G-CSF and CD34+ cell yields per liter processed during apheresis were significantly and negatively correlated with donor age (p=0.019), donor weight (p=0.011), and total CD34 dose (p=0.015). In contrast, peak circulating CD34+ counts were significantly higher in donors with higher baseline platelet (p=0.004) and mononuclear cell (p=0.027) counts. There was no significant relationship between donor gender or race and peak CD34+ mobilization response. In multivariate analysis, younger age was the single strongest factor associated with a favorable mobilization response (p=0.024); once age was in the model, donor weight and G-CSF dose no longer made significant contributions. In multivariate analysis, baseline platelet and mononuclear cell count (p=0.036 for both) continued to be strongly associated with a favorable mobilization response. Conclusions:In a healthy allogeneic pediatric population with an age range of 3 to 17 years, younger age is the driving factor determining the peak CD34+ mobilization response to G-CSF. Younger donors were smaller (lower weight) and thus received lower total doses of filgrastim, resulting in an inverse relationship between G-CSF dose and mobilization response, an opposite finding to that seen in adult PBSC donors. Higher baseline platelets and mononuclear cell counts were also predictors of more robust mobilization responses. Our data suggest that mobilizable cell reserves are greater in very young subjects, and that higher G-CSF dose or larger apheresis volumes are not necessary to achieve targeted cell yields in this population. Disclosures:No relevant conflicts of interest to declare.

Prophylactic Rituximab After Allogeneic Stem Cell Transplantation Prevents Steroid-Requiring Chronic Graft-Vs.Host Disease

AbstractAbstract 214There are no standard methods for the pharmacologic prevention of chronic GVHD (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Based on compelling biology implicating B cells in the pathophysiology of cGVHD and the utility of rituximab as therapy for established cGVHD, we performed a phase II trial of rituximab for the prevention of cGVHD after HSCT. Methods:64 patients in remission without active GVHD received rituximab (375 mg/m2) at 3, 6, 9 and 12 months after HSCT. Related and unrelated donor recipients of 5/6 or 6/6 HLA-matched PBSCs were eligible. Prophylactic IVIG infusions were permitted at investigator discretion. Chronic GVHD severity was assessed by the requirement for systemic corticosteroids, with a historical rate of steroid-requiring cGVHD within 1 year of transplantation of approximately 60% at our institution. Results:56 patients have been followed for at least 12 months from HSCT. One patient had a hypersensitivity reaction requiring treatment discontinuation and one patient was lost to follow-up, leaving 54 evaluable patients. The median patient age was 55 years (range 19 – 74); 25 were MRD recipients and 31 were URD recipients. 21 underwent myeloablative and 35 underwent reduced-intensity HSCT. Prior grade II-IV acute GVHD occurred in 6 patients (10.7%). Primary GVHD prophylaxis was sirolimus+tacrolimus (67.9%) or calcineurin inhibitor+methotrexate (32.1%), both without ATG. Overall, in the first year after HSCT there were 18 episodes of grade 3 toxicity and 8 episodes of grade IV toxicity without clear relationships to rituximab. There were 15 documented bacterial infections. Transient grade 3–4 neutropenia occurred in 11 subjects. 12 patients relapsed during the year after HSCT and 2 subjects died of non-relapse causes (pneumonitis and sepsis). The cumulative incidence of any cGVHD at 1 year from HSCT was 44.6%, however, the cumulative incidence of cGVHD requiring initiation of systemic corticosteroids was only 31.2%. When stratified by donor type, the incidence of all cGVHD and steroid-requiring cGVHD was 33.6 and 22.9% (MRD) and 52.3 and 37.0% (URD). Donor type, age, conditioning intensity, GVHD prophylaxis, donor gender or malignancy did not impact the incidence of cGVHD in a multivariable model. 8 additional patients required corticosteroids during the first post-transplant year for treatment of anorexia, pneumocystis pneumonia, pneumonitis or late acute GVHD. At 12 months, 50% of all patients had successfully discontinued all immunosuppressants and only 22.4% of all patients were on corticosteroids. Since anecdotally, myofascial and sclerodermatous cGVHD are treated effectively with rituximab, it is notable that only 1 patient had this subtype of cGVHD in contrast to the expected frequency of this manifestation of cGVHD in individuals not given rituximab. At 12 months from HSCT, relapse-free survival was 71.1% and overall survival was 88.6%. CD19+ B cells were very low during the first year post-HSCT, however patients without cGVHD demonstrated a trend toward enhanced B cell recovery at 6, 9 and 12 months from HSCT (6 months 0.58 vs. 0.28 × 106/L; 9 months 1.10 vs. 0.66 × 106/L; 12 months 1.09 vs. 0.76 × 106/L, all p=NS). Similarly, there was a trend for BAFF levels to be higher throughout the first year in patients without cGVHD (6 months 13.64 vs. 11.81; 9 months 12.30 vs. 9.57; 12 months 12.25 vs. 9.79, all p=NS). Among patients with cGVHD, there was a trend for BAFF levels to be higher in those who did not require systemic corticosteroids when compared to those that required steroids at 9 and 12 months (9 months 15.09 vs. 5.89 p=0.045; 12 months 11.86 vs. 7.14, p=0.25). 18 month B cell and BAFF data will be available at ASH. Conclusions.The use of rituximab at 3, 6, 9 and 12 months after allogeneic HSCT can reduce the rate of steroid-requiring cGVHD by up to 50% when compared with historical control data. The presence of enhanced B cell recovery, potentially related to higher BAFF levels found during the first year after HSCT, predicts freedom from cGVHD and a reduction in the severity of cGVHD among those affected. These data provide additional support for the hypothesis that B cells contribute to the development of cGVHD. A randomized trial should be performed to confirm these findings. Disclosures:No relevant conflicts of interest to declare.

Cyclosporine and Methotrexate Compared with Cyclosporine and Mycophenolate Mofetil as GVHD Prevention Regimens In Allogeneic Stem-Cell Transplantation From Unrelated Donors; Relative Outcomes Are Dependant on Disease Status at Transplantation

AbstractAbstract 2314Allogeneic stem cell transplantation (SCT) from matched unrelated donors (MUD) is a potentially curative approach for patients (pts) with hematologic malignancies and no sibling donors. Large progress has been made in MUD SCT, in recent years with better tissue typing and supportive care, however GVHD continues to be a major obstacle to cure. Several GVHD prevention regimens have been used, but there is currently no data to support one over the others. Over the last 10 years, 279 pts were given MUD SCT in a single institution. We historically used cyclosporine A and short-term methotrexate (15 mg/m2 on day1 and 10 mg/m2 on days 3 and 6, CSA/MTX, n=187). Over the last 3 years we used CSA with oral mycophenolate mofetil (MMF, 1 gr q12h, from day 0, n=92). We analyzed outcomes retrospectively. Acute and chronic GVHD were graded by the NIH consensus criteria. The median age was 52 years (range, 18–73). Diagnoses included AML/MDS (n=152), ALL (n=30), CML (n=12), myeloma (n=24), lymphoma (n=40) and others (n=21). Disease status at SCT was early (n=79), intermediate (n=81) or advanced stage (n=119). The donor was 10/10 (n=191), 9/10 (n=54) or ≤8/10 match (n=34). Conditioning was myeloablative (n=58), reduced intensity (RIC, n=145) or reduced toxicity myeloablative (RTC, n=76). All pts were given ATG during conditioning (15 mg/kg). The CSA/MMF regimen was less toxic than the CSA/MTX regimen. It allowed faster engraftment, day +11 and +14, respectively (p<0.001). Only 8% Vs 24% had ≥grade III mucositis (p=0.001) and 28% Vs 41% ≥grade III liver toxicity (p=0.04), respectively. Day 30 mortality, that is mostly attributed to regimen toxicity was 2.2% and 10.7%, respectively (p=0.04). Multivariate analysis (MVA) identified high comorbidity index (HR 2.5, p=0.05), advanced disease (HR 6.2, p=0.005), HLA mismatched donor (HR 2.4, p=0.03) and lymphoid malignancies (HR 2.8, p=0.03) as adverse prognostic factors for regimen-related mortality. GVHD prevention with CSA/MMF was protective (HR 0.4, p=0.02). However, CSA/MMF was less effective in preventing acute GVHD. The cumulative incidence of grade III-IV acute GVHD was 29% and 18%, respectively (p=0.005), with related deaths occurring in 22% and 9% of all pts, respectively (p=0.005). MVA identified HLA mismatched donor (HR 3.4, p=0.001), CSA/MMF (HR 2.4, p=0.004), and male gender (HR 2.5, p=0.05) as adverse factors, while RIC/ RTC was protective from severe acute GVHD and GVHD-related deaths (HR 0.4, p=0.01). The net effect was that the cumulative incidence of non-relapse mortality (NRM) with both regimens was equivalent. The most important factor predicting for overall survival (OS) was disease status at SCT with estimated 5-year OS rates of 52%, 40% and 14%, for pts with early, intermediate and advanced disease status, respectively (p<0.001). MVA identified advanced disease (HR 2.9, p<0.001), HLA mismatched donor (HR 1.4, p=0.05) and age>55 (HR 1.4, p=0.08) as adverse factors while RIC/RTC was favorable in this dataset (HR 0.7, p=0.05). The GVHD prevention regimen had no impact on OS. However, when pts were stratified based on disease status, the GVHD prevention regimen had a major impact. In early stage disease, OS was 65% and 42%, after CSA/MTX and CSA/MMF, respectively (p=0.05), with CSA/MMF identified as a poor prognostic factor in MVA; HR 1.9 (p=0.06). This was predominantly due to excess deaths of GVHD in this group. On the other hand, in pts in advanced disease, OS was better with CSA/MMF; 20% and 12%, respectively (p=0.04). MVA identified age>55 (HR 1.6, p=0.04), mismatched donor (HR 2.2, P=0.007) and lymphoid malignancies (HR 1.9, p=0.03) as poor prognostic factors, while CSA/MMF was favorable (HR 0.5, P=0.005). This was predominantly due to less deaths due to relapse in this subgroup. In conclusion, the GVHD prevention regimen has a major impact on outcome after MUD SCT. CSA/MMF is a less toxic regimen and allows prompt engraftment, but is less effective in preventing GVHD. In early stage disease, where outcome is dominated by NRM, a more effective GVHD prevention regimen such as CSA/MTX is needed. However in pts with advanced disease, who are also more susceptible to regimen toxicity, a less intensive regimen, that also better preserves GVL, such as CSA/MMF, may be associated with a better outcome. The GVHD prevention regimen selected may need to be tailored to pt and disease characteristics. These observations merit further investigation in randomized prospective studies. Disclosures:No relevant conflicts of interest to declare.

A Retrospective Comparison of Tacrolimus Vs. Cyclosporine for Immunosuppression After Allogeneic Hematopoietic Cell Transplantation with G-CSF-Mobilized Blood Cells

AbstractAbstract 2319 Background:Graft-versus-host disease (GVHD) is a common immunologic complication after allogeneic hematopoietic cell transplantation (HCT). Cyclosporine or tacrolimus in combination with other agents represent widely accepted standards of care as immunosuppressive regimens after HCT. Results of open-label randomized prospective phase III studies have indicated that the risk of grades II-IV acute GVHD after bone marrow transplantation with related or unrelated donors is lower with the use of tacrolimus as compared to cyclosporine, in combination with methotrexate. The current study was carried out to compare results with tacrolimus versus cyclosporine after HCT with G-CSF-mobilized blood cells. Patients and methods:The study cohort included 510 consecutive patients who received a first G-CSF-mobilized blood cell graft from related or unrelated donors after high-intensity conditioning for treatment of hematological malignancies between 7/1/2003 and 2009 at our center. All patients received ursodeoxycholic acid from 2 weeks before conditioning until 90 days after HCT to prevent hepatic complications, and all patients received immunosuppression with either tacrolimus or cyclosporine in combination with methotrexate after HCT. Endpoints included grades II-IV acute GVHD, grades III-IV acute GVHD, chronic GVHD, end of treatment for chronic GVHD, overall survival, disease-free survival, recurrent malignancy and nonrelapse mortality. Multivariate Cox regression models were used to evaluate hazard ratios for these endpoints with tacrolimus as compared to cyclosporine. The models were adjusted for patient age, donor type, recipient and donor gender combination, disease type, disease risk category, use of total body irradiation in the conditioning regimen, and year of HCT. The analysis was carried out as of July, 2010. Results:The median age of patients was 47 (range, 1 to 66) years. Diagnosis at HCT was acute myeloid leukemia in 200 (39%) patients, acute lymphoblastic leukemia in 73 (14%), chronic myeloid leukemia in 49 (10%), myelodysplastic syndrome or myeloproliferative disorders in 160 (31%) and other lymphoid malignancies in 28 (5%). Total body irradiation was used for conditioning in 168 (33%) patients. Of the 510 patients, 277 (54%) had HLA-matched related donors, 203 (40%) had HLA-matched unrelated donors, and 30 (6%) had HLA-mismatched related or unrelated donors. Outcomes according to immunosuppression with tacrolimus or cyclosporine are shown in Table 1. Multivariate analysis showed no statistically significant differences between tacrolimus and cyclosporine for any of the endpoints tested (Table 2), although the results showed a trend suggesting that the risk of non-relapse mortality might be lower with tacrolimus as compared to cyclosporine. Conclusion:In this retrospective analysis, tacrolimus offered no statistically significant advantage over cyclosporine for preventing grades II-IV acute GVHD after HCT with G-CSF-mobilized blood cells, and results for other outcomes also showed no statistically significant differences. Although our data support the hypothesis that either regimen could be an acceptable standard of care for immunosuppression, the number of patients analyzed in this study is not sufficient to completely exclude clinically meaningful differences in outcomes with the two regimens.Table 2Multivariate analysis of outcomes with tacrolimus compared to cyclosporineEndpointNo. of eventsHazard ratio (95% CI)PGrades II-IV acute GVHD3520.95 (0.7–1.3)0.76Grades III-IV acute GVHD531.30 (0.6–2.9)0.52Chronic GVHD2030.84 (0.6–1.2)0.39End of systemic treatment for chronic GVHD580.85 (0.4–2.1)0.72Overall survival1970.77 (0.5–1.2)0.21Disease-free survival2320.88 (0.6–1.3)0.51Recurrent malignancy1391.13 (0.7–1.8)0.62Nonrelapse mortality930.61 (0.3–1.1)0.10 Disclosures:Off Label Use: Tacrolimus and cyclosporine for immunosuppression after allogeneic hematopoietic cell transplantation.

Pediatric patients receiving ABO-incompatible living related liver transplantation exhibit higher serum transforming growth factor-β1, interferon-γ and interleukin-2 levels

ABO-incompatible liver transplantation (LTx) is becoming more common in response to the paucity of liver allografts. Several studies have expressed concern about the effect of ABO compatibility on graft survival. To evaluate the differences in serum cytokine levels between ABO-incompatible (ABO-i) and ABO-compatible (ABO-c; includes ABO-compatible and identical) pediatric LTx recipients during regular outpatient follow-up. Note that, in the field of organ transplantation, transplants are categorized as incompatible, compatible or identical; accordingly, these are the terms we use in the paper. A clinical outpatient study measuring serum transforming growth factor (TGF)-β1, interferon (IFN)-γ, interleukin (IL)-2 and IL-10 in 43 living related liver transplantation (LRLT) recipients, of whom 36 received ABO-c LRLT (34 were ABO-identical and 2 were non-identical) and 7 ABO-i LRLT. Serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase and bilirubin were measured as part of the patients' regular follow-up visits. There were no differences between the ABO-c and ABO-i groups in terms of recipient's age [mean 12.6 vs. 11.1years (y)], post-LTx duration (mean 7.3 vs. 7.3y), donor's age (mean 35.5 vs. 34.6y), body weight (28.9±2.9 vs. 27.9±6.9kg), or gender (19 female and 17 male vs. 4 female and 3 male). Serum TGF-β1, IFN-γ and IL-2 were significantly higher in the ABO-i group than in the ABO-c group. IL-10, however, did not differ between the two groups. There was a tendency toward higher γGTP levels in the ABO-i group, but this difference did not reach significance. ABO-incompatible LRLTx patients have higher serum TGF-β1, IFN-γ and IL-2 levels as measured at regular outpatient visits. As a result, they face a higher risk of T-helper 1 cell polarization, which could make graft rejection more likely.

The Effects of 17-β Estradiol on Enhancing Proliferation of Human Bone Marrow Mesenchymal Stromal Cells In Vitro

Human bone marrow mesenchymal stromal cells (MSCs) with self-renewal and multiple differentiation potentials are considered a possible cell source for tissue engineering and regenerative medicine. However, the limited amount of MSCs in bone marrow and the loss of differentiation capacity following in vitro expansion restrict their practical application. Effective improvement of MSC proliferation is necessary for the clinical application of MSC-based tissue engineering. The effects of estrogen supplements on proliferation and characterizations of human MSCs were investigated at the present study. Supplements of 17-β estradiol (E2) significantly increase the proliferation of human MSCs in vitro. The dose range of E2 to significantly increase MSC proliferation differs in the gender of MSC donor. E2 supplementation in cell proliferation maintains characterizations of MSCs, including cell surface markers, and osteogenic and adipogenic differentiation capacities. These data indicate that estrogen treatment can play an important role in improving human MSCs' expansion in vitro, which will effectively facilitate MSCs' function in the practical application of tissue engineering and regeneration.