Gender Mismatch Research Articles

The Impact of Gender Mismatch on Survival After Heart Transplantation

Gender mismatched have poorer outcomes in retrospective single centre studies in the literature for kidneys, hearts and livers. We aim to evaluate the impact of gender mismatch in adults undergoing heart transplantation in the UK.

Gender Mismatch with Female Donor Hearts to Male Recipients: A Single Center Analysis

Registry data has shown that using female donors for male recipients in heart transplantation is associated with increased mortality. Our purpose was to examine whether this practice led to increased 1-year mortality at our institution.

The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors: An Analysis of the United Network for Organ Sharing Registry.

The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

Understanding consumer engagement with celebrity-endorsed E-Cigarette advertising on instagram

Considering that e-cigarette use is often glamorized on social media through celebrity endorsements, this study examined the effects of product-celebrity image congruence, consumer-celebrity risk-oriented image congruence, and parasocial identification on consumer engagement with celebrity-endorsed e-cigarette advertising on Instagram. Results indicated that high product-celebrity image congruence, and high consumer-celebrity risk-seeking image congruence, led to significantly more positive ad attitude and greater intention to spread eWOM and use e-cigarettes. Consumer-celebrity risk-averse image congruency, meanwhile, led to significantly less favorable ad attitude and lower intention to spread eWOM and use e-cigarettes. Post-hoc analyses further suggested that smoking status and gender (match vs. mismatch between consumer and celebrity) had a significant influence on processing of, and consumer engagement with, e-cigarette Instagram ads. Additionally, parasocial identification moderated the effects of celebrity-product image congruence, and consumer-celebrity risk-oriented image congruence, on key engagement measures. Theoretical and managerial implications for researchers, marketers, and policy makers are discussed.

Wie generisch ist das generische Maskulinum? Über Genus und Sexus im Deutschen

This paper examines whether gender features (masculine, feminine, neuter) in German have to be interpreted semantically, along their specific gender, or whether they allow for a gender unrelated interpretation. As to this, two experiments with two different classes of nouns (gender marked and sex marked nouns vs. gender marked and sex neutral nouns) were conducted. The first experiment supports the view that in their function as nominal predicates masculine nouns, contrary to feminine (and neuter) nouns, have the widest extension – which confirms the existence of a ‘Generic Masculine’ (Generisches Maskulinum). On the other hand, the second experiment shows that in their function as subjects masculine nouns, contrary to feminine (and neuter) nouns, are the least flexible agreement controllers – hardly allowing for gender mismatches. Thus, masculine nouns behave differently depending on whether they appear as controllers/sources of agreement or as targets of agreement. The findings are supplemented by corpus data.

Teacher gender, and expectation of reading achievement in New Zealand elementary school students: essentially a barrier?

ABSTRACTBoys continue to demonstrate lower average achievement in reading than girls. The influence of teacher gender has been explored among the factors explaining this scenario but with mixed results. Further, although teacher expectations have affected student academic outcomes, and student gender-related stereotypical notions have shaped such expectations, the role of teacher gender within this scenario has been neglected. The current study was conducted with a sample of elementary schools, in New Zealand (a national setting where essentialist gender attitudes have existed and where policies to implement scholastic gender equity have been critiqued as unsuccessful). The influence of teacher gender and of a teacher-student gender match and mismatch on teacher’s expectations of their elementary student reading achievement, was tested via hierarchical linear modeling. Male teachers’ expectations were found to be lower for students of both genders in reading and negative implications for male teachers and their students’ reading achievement were revealed.

Promoting sustainability in a college café by opposite-sex cashiers

PurposePeople engage in green consumption for many reasons, both conscious and unconscious. This paper aims to draw on evolutionary psychology to propose that hard-wired mating strategies encourage both men and women to increase their green consumption in the presence of members of the opposite sex.Design/methodology/approachObservations were conducted on 324 students who purchased cold drinks in disposable cups from a college café. The students were offered the choice of adding 20 cents to their purchase for a bio-degradable cup.FindingsOverall, 160 students agreed to pay the premium for a bio-degradable cup, with green purchases 46 per cent higher among women and 61 per cent higher among men when facing a cashier of the opposite sex.Originality/valueThe findings suggest that the activation of mating cues prompts students to display prosocial, altruistic behavior and/or to engage in conspicuous consumption (i.e. agreeing to pay more for the sustainable product). The study was conducted in the field using naïve participants and demonstrates the application of evolutionary psychology to green marketing. It also adds to what is a surprisingly small literature on the effect of employee–customer gender mismatch.

P1451Gender related differences in echocardiographic findings post heart transplantation -Impact of sex-mismatch on biventricular function

Purpose: The aim of this study was to investigate gender-specific differences in HTx patients and if gender mismatch affect echocardiographic parameters of size and function.

Processing gender agreement and word emotionality: New electrophysiological and behavioural evidence

Abstract The present article reports an ERP study with two experiments designed to assess the influence of emotional adjectives on sentence processing by means of a gender agreement (grammaticality) judgment task. Participants were shown transitive sentences in Spanish presented word-by-word, with a complex object-NP consisting of a noun + an adjective + some additional material. ERPs were recorded at the critical adjectives, which could be either emotionally unpleasant, neutral, or pleasant, and could either agree (match) or fail to agree (mismatch) in gender with the modified noun. Results replicate the typical ERP signatures of morphosyntactic errors. Specifically, larger amplitudes for LAN and P600 components were found in sentences with a gender mismatch in both experiments. However, ERP components did not show any differences between emotional and neutral adjectives in these sentences. Only in Experiment 2 was a significant interaction found between grammaticality and emotionality. Thus, in the 500–700 ms window larger amplitudes emerged for neutral words than for emotional words in match sentences. Likewise, a significant interaction between grammaticality and emotionality in the participants’ performance revealed that the presence of emotional adjectives did facilitate the detection of gender errors. Overall, these results show that during sentence reading syntactic error detection seems to occur in an encapsulated manner, although performance may indeed be facilitated by the presence of emotional words.

The impact of multidisciplinary care on early morbidity and mortality after heart transplantation.

The impact of multidisciplinary care on outcome after heart transplantation (HTx) remains unclear. This retrospective study investigates the impact of multidisciplinary care on the primary end point 1-year all-cause mortality (ACM) and the secondary end point mean acute cellular rejection (ACR) grade within the first postoperative year. This study includes a total 140 HTx recipients (median age: 53.5 years; males: 80%; donor/recipient gender mismatch: 38.3%; mean length of in-hospital stay: 34 days; mean donor age: 41 years). Multidisciplinary care was implemented in 2008, 66 HTx recipients had operation in 2000-07 and 74 patients had HTx thereafter (2008-14). Non-ischaemic dilated cardiomyopathy was more prevalent in HTx recipients of 2000-07 (63.6 vs 43.2%; P = 0.024). Pre-transplant mechanical circulatory support was more frequent in 2008-14 (9.1 vs 24.3%; P = 0.030). Groups were not different for pre-transplant cardiovascular risk factors or other comorbidity, invasive haemodynamics or echocardiographic parameters. In-hospital and 1-year ACM were numerically lower in 2008-14 (16.2 vs 22.2%; 18.9% vs 25.8%; P = 0.47/0.47, respectively). In 2000-07, pre-transplant weight and diabetes mellitus predicted in-hospital ACM (odds ratio -0.14, P = 0.02; OR 5.24, P = 0.01, respectively) while post-transplant length of in-hospital stay was related with in-hospital ACM (odds ratio -0.10; P = 0.016) and 1-year ACM (odds ratio -0.07; P = 0.007). In 2000-07, the mean grade of ACR within the first postoperative year was higher (0.65 vs 0.20; P < 0.0001) and ≥moderate ACR was associated with in-hospital mortality (χ2 = 3.92; P = 0.048). Multidisciplinary care in HTx compensates post-transplant risk associated with pre-transplant disease and has beneficial impact on the incidence of ACR and ACR-associated early mortality.

HLA Mismatching Favoring Host-Versus-Graft NK Cell Activity Via KIR3DL1 Is Associated With Improved Outcomes Following Lung Transplantation.

Chronic lung allograft dysfunction (CLAD) is linked to rejection and limits survival following lung transplantation. HLA-Bw4 recipients of HLA-Bw6 grafts have enhanced host-versus-graft (HVG) natural killer (NK) cell activity mediated by killer cell immunoglobulin-like receptor (KIR)3DL1 ligand. Because NK cells maypromote tolerance by depleting antigen-presenting cells, we hypothesized improved outcomes forHLA-Bw4 recipients of HLA-Bw6 grafts. We evaluated differences in acute cellular rejection and CLAD-free survival across 252 KIR3DL1+ recipients from University of California, San Francisco (UCSF). For validation, we assessed survival and freedom from bronchiolitis obliterans syndrome (BOS), retransplantation, or death in 12845 non-KIR typed recipients from the United Network for Organ Sharing (UNOS) registry. Cox proportional hazards models were adjusted for age, gender, ethnicity, transplant type, and HLA mismatching. HVG-capable subjects in the UCSF cohort had a decreased risk of CLAD or death (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.36-0.88) and decreased early lymphocytic bronchitis. The HVG effect was not significant in subjects with genotypes predicting low KIR3DL1 expression. In the UNOS cohort, HVG-capable subjects had a decreased risk of BOS, retransplant, or death (HR 0.95, 95% CI 0.91-0.99). Survival improved with the higher-affinity Bw4-80I ligand and in Bw4 homozygotes. Improved outcomes in HVG-capable recipients are consistent with a protective NK cell role. Augmentation of NK activity could supplement current immunosuppression techniques.

1025 SLEEP APNEA AND KIDNEY TRANSPLANT GRAFT SURVIVAL: FINDINGS FROM AN 18-YEAR (1997–2015) HISTORICAL COHORT STUDY

Sleep apnea has been linked to the acceleration of renal failure in end-stage renal disease (ESRD). However, few studies have examined the association of sleep apnea to kidney functioning in ESRD patients post-transplant. A historic cohort study of kidney transplant recipients with a failed graft from a single-center examined the association between sleep apnea and kidney transplant graft survival time. Adult patients who were transplanted and failed or died with a functioning graft during the designated study time period (January 1, 1997-September 1, 2015) were included (n=299). Sleep apnea was defined as a diagnosis in a patient’s medical record documented prior to graft failure. Graft survival time was defined as graft failure and/or cardiovascular death with a functioning graft, two common outcomes of kidney transplantation associated with ESRD. Non-cardiovascular related deaths with a functioning graft were censored. A Cox regression, stratified by year of transplant surgery, modeled the association of diagnosed sleep apnea with graft survival time. Using backward elimination, models were adjusted for age, gender, functional status, and antigen mismatch. Sleep apnea prevalence in this cohort was 17%. Due to a significant (p ≤0.01, adjusted model) sleep apnea by transplant year heterogeneity for graft survival time, Cox regression models were stratified. For patients transplanted between 1997–2008, sleep apnea was associated with a decreased (albeit non-significantly) risk of graft failure and/or cardiovascular death (adjusted Hazard Ratio (HR) = 0.67, 95% CI, 0.45–1.01). For patients transplanted between 2009–2015, sleep apnea statistically significantly increased graft failure and/or cardiovascular death risk (adjusted HR = 2.94, 95% CI, 1.12–7.75). In a single-center cohort of kidney transplant recipients with a failed graft, sleep apnea increased the risk of graft failure and/or cardiovascular death with a functioning graft nearly three-fold among patients transplanted between 2009–2015. Further research is needed to better understand this relationship and whether prevention strategies, including treating sleep apnea, might increase longevity in kidney transplant patients. Data abstraction continuing through January 1, 2017 will allow evaluation of a twenty-year follow-up of this historical cohort study. None

(1275) - Effect of Gender Mismatch on Outcome in Lung Transplantation

(1275) - Effect of Gender Mismatch on Outcome in Lung Transplantation

Voice gender and the segregation of competing talkers: Perceptual learning in cochlear implant simulations.

Two experiments explored the role of differences in voice gender in the recognition of speech masked by a competing talker in cochlear implant simulations. Experiment 1 confirmed that listeners with normal hearing receive little benefit from differences in voice gender between a target and masker sentence in four- and eight-channel simulations, consistent with previous findings that cochlear implants deliver an impoverished representation of the cues for voice gender. However, gender differences led to small but significant improvements in word recognition with 16 and 32 channels. Experiment 2 assessed the benefits of perceptual training on the use of voice gender cues in an eight-channel simulation. Listeners were assigned to one of four groups: (1) word recognition training with target and masker differing in gender; (2) word recognition training with same-gender target and masker; (3) gender recognition training; or (4) control with no training. Significant improvements in word recognition were observed from pre- to post-test sessions for all three training groups compared to the control group. These improvements were maintained at the late session (one week following the last training session) for all three groups. There was an overall improvement in masked word recognition performance provided by gender mismatch following training, but the amount of benefit did not differ as a function of the type of training. The training effects observed here are consistent with a form of rapid perceptual learning that contributes to the segregation of competing voices but does not specifically enhance the benefits provided by voice gender cues.

Impact of Alemtuzumab Scheduling on Graft-versus-Host Disease after Unrelated Donor Fludarabine and Melphalan Allografts

Alemtuzumab conditioning is highly effective at reducing the incidence of acute and chronic graft-versus-host disease (GVHD) in reduced-intensity fludarabine and melphalan transplantation with cyclosporine monotherapy. Less frequent and lower dose scheduling may be used with sibling donors, but an optimal regimen for matched unrelated donors has not been defined. In this retrospective observational study of 313 patients, the incidence and severity of GVHD was compared in patients receiving 3 different dose schedules: the standard 100-mg regimen (20 mg on days –7 to –3), 60 mg (30 mg on days –4 and –2), or 50 mg (10 mg on days –7 to –3). Patients treated with 100 mg, 60 mg, or 50 mg developed acute GVHD grades I to IV with an incidence of 74%, 65%, and 64%, respectively, whereas 36%, 32%, and 41% developed chronic GHVD. An excess of severe acute grades III/IV GVHD was observed in the 50-mg cohort (15% versus 2% to 6%; P = .016). The relative risk of severe acute grade GVHD remained more than 3-fold higher in the 50-mg cohort compared with the 100-mg cohort after adjustment for differences in HLA match, age, gender mismatch, cytomegalovirus risk, and diagnosis (P = .030). The findings indicate that the 60-mg alemtuzumab schedule was comparable with the 100-mg schedule, but more attenuated schedules may increase the risk of severe grade GVHD.

Donor–recipient size matching and mortality in heart transplantation: Influence of body mass index and gender

The International Society for Heart and Lung Transplantation (ISHLT) guidelines advise against inappropriate weight match (IWM) for heart transplant, defined as donor weight <70% of recipient's weight. Few studies have explored in detail this size-matching recommendation, especially with regard to body mass index (BMI) and gender matching. We aimed to determine whether any difference could be observed between size-matching in obese and non-obese recipients with regard to mortality after cardiac transplantation. Data from 52,455 adult heart transplants (recipients ≥18 years of age) between 1994 and 2013 were obtained from the ISHLT Registry. We defined the following subgroups of patients based on BMI: underweight, BMI <18.5; non-obese, BMI 18.5 to 30; and obese, BMI >30. The end-points were all-cause 30-day mortality and cumulative mortality. IWM was associated with increased 30-day mortality (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.01 to 1.43, p = 0.041) and cumulative mortality (hazard ratio [HR] = 1.14, 95% CI 1.07 to 1.22, p < 0.001). In non-obese recipients, IWM was associated with increased 30-day mortality (OR = 1.89, 95% CI 1.48 to 2.41, p < 0.001) as well as cumulative mortality (HR = 1.27, 95% CI 1.15 to 1.41, p < 0.001), whereas, for obese recipients, IWM was not associated with 30-day or cumulative mortality. Male recipients of female allografts (HR = 1.08, 95% CI 1.04 to 1.12, p < 0.001) as well as female recipients of male allografts (HR = 1.07, 95% CI 1.02 to 1.13, p = 0.003) had increased cumulative mortality compared with gender-matched transplants. There was no interaction between IWM and gender mismatch. Our results indicate that donor weight <70% of recipient weight increases mortality in non-obese heart transplant recipients, but not in obese transplant recipients. Gender mismatch increases mortality independently of weight match.

Therapeutic Cyclosporine Exposure Measured As Area Under the Curve (AUC) Significantly Influences the Outcome after Allogeneic Hematopoetic Stem Cell Transplant (alloHSCT)

Introduction: Prevention of Graft versus host disease (GVHD) forms the mainstay of obstacle in the successful outcome of alloHSCT. Various strategies are employed but combination of calcineurin inhibitors with methotrexate or mycophenolate is the commonest preventative measure used. Cyclosporine is dosed according to trough (C0) levels and the optimum level is defined as between 200 and 300 ng/ml. Daily doses are adjusted to achieve the therapeutic levels. As there can be fluctuations in the daily levels, it was postulated that area under the curve (AUC) extrapolated from daily levels may be more useful to define the optimum cyclosporine exposure for prevention of GVHD. Hence this retrospective analysis was carried out to evaluate if cyclosporine AUC for first 14 days has correlation with the incidence of GVHD.Methods: 549 patients who received allograft and had cyclosporine C0 levels available for first 14 days were included in the analysis. The patient population included 353 males (64.3%) and 196 females (35.7%) with a median age of 44 yr. (range: 16-71). Underlying diagnosis included Ac. Leukaemia (n=319, 58.1%), Chr. Leukaemia (n=42, 7.7%), lymphoma (n=119, 21.7%), myeloma (n=57, 10.4%) or other (n=12, 2.2%).Donor was matched unrelated (n=330, 60.1%), sibling (n=204, 37.2%) or cord (n=15, 2.7%). Stem cell source was PBSC (n=454, 82.7%), BM (n=78, 14.2%), both (n=2, 0.4%) or cord blood (n=15, 2.7%). 415 patients had RIC (75.6%) and 134 had full intensity SCT (24.4%). Alemtuzumab or ATG was used in conditioning in 311 cases (56.6%). The target Cyclosporine AUC with a daily level of 200 was predicted as 2600, 2470 for cyclosporine level of 190 and 2730 for levels of 210.Results: The median AUC for the entire cohort was 3338 (range: 370-6390). Only 56 cases (10.2%) had AUC below 2600. Incidence of AGVHD was significantly higher with use of PBSC (53.7% vs. 21.7%, p<0.001), NHL (66.3% vs. 44.8%, p=0.002) and Alemtuzumab/ATG use (55.9% vs. 40.8%, p<0.001), non-TBI conditioning (57.3% vs. 38.7%, p<0.001) but there was no difference with gender, gender mis-match, intensity of conditioning, CMV match or underlying malignancy. Risk of GVHD was not related to cyclosporine AUC below 2600 (41.2% vs. 50.3%, p=0.2), below 2470 (38.6% vs. 50.3%, p=0.14) or below 2730 (49.4% vs. 49.4%, p=0.99). Similarly incidence of CGVHD was higher with use of PBSC (66.7% vs. 36.6%, p<0.001), Alemtuzumab/ATG (66.2% vs. 53.8%, p=0.003), RIC (64.1% vs. 50.7%, p=0.013) and prior AGVHD (100% vs. 22%, p<0.0001). There was no effect of gender, gender mis-match, underlying malignancy and cyclosporine AUC. AUC did not influence the incidence of AGVHD or CGVHD when the analysis was done separately for full and reduced intensity transplants. The median OS from HSCT was 4.9 yr. (0.01-23.8 yr.). Even though incidence of AGVHD or CGVHD was not influenced by cyclosporine AUC, OS was significantly lower for AUC below 2470 (2.2 vs. 4.9 yr., p=0.0002), below 2600 (2.5 vs. 5.0 yr., p=0.0001) and below 2730 (2.1 vs. 4.6 yr., p<0.0001). By multi-variate analysis, Alemtuzumab/ATG (RR: 1.55, 95% CI: 1.04-2.3, p=0.031) and AUC below 2600 (RR: 1.9, 95% CI: 1.3-2.8, p<0.001) were independently associated with inferior OS. Patients with both the factors had lowest OS (none: 7.5 yr.; one: 5yr., both: 1.1 yr.; p<0.0001).Conclusion: This retrospective analysis had high proportion of cases receiving Alemtuzumab/ATG based GVHD prophylaxis and shows that even though there is no effect of cyclosporine AUC on the incidence of either AGVHD or CGVHD, patients receiving Alemtuzumab/ATG with sub-therapeutic cyclosporine AUC have poor OS. This raises the possibility that in this group of patients it is imperative to have target cyclosporine levels in first 14 days. The duration of target cyclosporine levels before tapering the doses needs to be established to improve OS without increasing the toxicity. DisclosuresSomervaille:Imago Biosciences: Consultancy; Novartis: Consultancy, Honoraria. Bloor:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria; GSK: Consultancy, Speakers Bureau.

Refined Hepatic Grading System Improves Risk Stratification of Long-Term Outcomes in the Patients Developing Chronic Gvhd

Background: Chronic GVHD (cGVHD) is a syndrome with diverse clinical features resembling autoimmune disorders. cGVHD affects long-term outcomes of allogeneic HCT, resulting in significant morbidity and mortality. Scoring the severity of cGVHD has been proposed with recent changes in the grading system of cGVHD based on the NIH consensus criteria (NCC) in 2015. Grading of liver GVHD is based on the severity of liver enzyme elevation both in NCC in 2005 and 2015. The cutoff of liver enzyme profiles for liver GVHD grading is arbitrarily determined but never been validated. In this study we attempted to evaluate 3 grading systems of hepatic parameters used in 1) NCC 2005, 2) NCC 2015, and 3) the common terminology criteria for adverse events (CTCAE) version 4.0. We also have adopted binary recursive partitioning (rpart) to define the optimal cut-off that provides the best risk stratification to overall survival (OS) after development of cGVHD.Methods: A retrospective review was conducted to compare the hepatic grading systems using liver enzyme parameters used in NCC 2005, NCC2015 and CTCAE v4.0. We reviewed 336 patients who developed cGVHD after allogeneic HCT performed between 2002 and 2014. Long-term outcomes including OS and non-relapse mortality (NRM) after the occurrence of cGVHD were analyzed using the 3 hepatic grading systems. Using rpart, we determined the optimal value for each component of the liver enzyme profile (i.e. AST, ALT, ALP and bilirubin level) was which could identify the best risk stratification of OS. A refined hepatic grading system was generated based on the cut off of ALP and bilirubin level proposed by rpart method, which divided the patients into three groups: low (bilirubin <14 mmol/L and ALP < 146 IU/L), intermediate (bilirubin level ≥14 mmol/L or ALP ≥ 146 IU/L) and high risk (both) . OS and NRM were also compared according to the refined hepatic grading system.Results: Out of 336 patients, 181 had liver involvement of cGVHD. The 3 year OS rate was 74.9% (66.7-81.3%) in the group developing liver GVHD, while that was 67.0% (57.7-74.7%) in the group without liver GVHD (p=0.629). There is no difference of non-relapse mortality (NRM) between patients with or without liver GVHD (14.4% vs. 17.2%; p= 0.661).In the patients developing liver GVHD, 3 hepatic grading systems were evaluated with respect to OS and NRM after onset of cGVHD. None of the 3 grading systems could stratify the patients statistically according to OS (p=0.211 for NCC 2005; p=0.423 for NCC 2015; p=0.461 for CTCAE4.0) or to NRM (p=0.615 for NCC 2005; p=0.327 for NCC 2015; p=0.941 for CTCAE v4.0). Using rpart, we found that 1) bilirubin level ≥14 mmol/L (p=0.01) and 2) ALP ≥ 146 IU/L (p=0.059) are associated with shorter OS, 2) AST and ALT levels were not associated with OS or NRM.A refined hepatic grading system was generated with assignment of a score to each risk factor. A score of 1 was assigned to bilirubin ≥14 mmol/L and ALP ≥ 146 IU/L, each. Total score was calculated with risk score 0 (n=54, 30.0%), risk score 1 (n=85, 57.2%) and risk score 2 (n=41, 22.8%). This hepatic grading system could stratify the patients according to their OS (p=0.015): 89.6% in low vs. 71.8% in intermediate vs. 58.0% in high risk group after onset of cGVHD.Then, we have applied the refined hepatic grading system into all 336 patients developing cGVHD regardless of organ involvement. As expected, the hepatic grading system can stratify 336 patients according to OS: 79.6% in low vs. 65.4% in intermediate vs. 53.9% in high risk group after onset of cGVHD (p=0.001); according to NRM: 11.9% in low vs. 17.2% in intermediate vs. 26.1% in high risk group after onset of cGVHD (p=0.089).Multivariate analysis was performed including 9 covariates including refined hepatic grading system, liver involvement of cGVHD, cGVHD subtype, cGVHD onset < 5 months, age (by decade), platelet counts, HLA match, gender mismatch, and T cell depletion, and confirmed that the refined hepatic grading system is an independent prognostic factor for OS (p=0.003, HR 0.491) in addition to cGVHD onset <5 months and HLA match.Conclusions: None of hepatic grading systems could stratify the patients according to OS/NRM after development of cGVHD. The refined hepatic grading system using bilirubin ≥14 mmol/L and ALP ≥ 146 IU/L at onset of cGVHD defined by the rpart method, could improve risk stratification of the patients developing cGVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Donor Type and Disease Risk Predict the Success of Allogeneic Hematopoietic Cell Transplantation (HCT): A Single Center Analysis of 613 Adult HCT Recipients Using a Modified Composite Endpoint

Donor Type and Disease Risk Predict the Success of Allogeneic Hematopoietic Cell Transplantation (HCT): A single Center Analysis of 613 Adult HCT Recipients Using a Modified Composite EndpointIntroductionThe success of allogeneic HCT is based on long term survival, free of relapse or morbidity as commonly encountered when patients develop graft versus host disease (GVHD). The Bone marrow transplant clinical trials network (BMTCTN) recently incorporated a composite endpoint to determine success rate in ongoing clinical trials. The new composite endpoint of GVHD free, relapse free survival (GRFS) includes the factors of acute GVHD grade 3-4, relapse, death and chronic GVHD requiring systemic immunosuppression. As the decision to start patients on immunosuppression for chronic GVHD can be subjective and physician dependent, we elected to assess the success of allogeneic HCT using a more objective endpoint m-GRFS where the clinically significant negative events are acute GVHD grade 3-4, moderate-severe chronic GVHD, disease relapse and Death at 1 and 2-year post HCT.MethodsSix hundreds and thirteen patients who underwent a first allogeneic HCT after a HLA-identical sibling (MRD, n=212), 10/10 matched unrelated donor (MUD, n=251) or T-replete haploidentical donor with post-transplant cyclophosphamide (HIDT, n=150) were included in this analysis. Patient, Disease and Transplant related variables were prospectively documented and obtained from our institutional database. The Kruksall-Wallis test was used to compare continuous variables and the Chi-squared test for categorical variables. OS, DFS and m-GRFS were estimated by the Kaplan-Meier (K-M) method. Log-log transformed confidence intervals for OS, DFS and GRFS were calculated. Comparison of m-GRFS between demographic subgroups and between clinical subgroups were evaluated using the log-rank test for the entire study period and using the Wald test for a select time point. Competing risks analysis was performed to disentangle the components of GRFS. Grade III/IV acute GVHD, mod-severe chronic GVHD, relapse and death were considered as competing risks and cumulative incidences of these endpoints were calculated. Patients were considered to have met the endpoint once any of the components occurred. Cox regression analysis was conducted to examine the impact of donor, demographic and clinical factors on the primary endpoint of modified GRFS. The proportional hazards assumption was checked by temporarily including and testing time-dependent variables and the variables in the final model passed the proportionality test. The adjusted GRFS for one characteristic was calculated as the average survival of the whole sample, assuming that everyone in the sample had this characteristic.ResultsThe median follow-up was 50.2 months. Patients characteristics were as follows: median age 53 years (18-77), male 56%, reduced intensity/non-ablative 49%, AML 37%, ALL 13%, MDS/MPD 24%, bone marrow graft 19%, HCT-comorbidity index >=3 in 39%, and high/very high DRI 34%. The unadjusted Kaplan-Meier estimates for 1- and 2-year m-GRFS were 36% (95%CI 32%-40%) and 28% (95%CI 25%-32%). The 2-year m-GRFS for MRD recipients was 30% (24-36%), MUD 24% (19-30%) and HIDT 33% (26-41%). The most common event at 2 years post HCT was chronic GVHD (39%) followed by relapse (31%), acute GVHD 3-4(20%) and death (10%). After adjusting for age, gender, diagnosis, conditioning intensity, donor type, cell source, HCT-CI, DRI , donor-recipient gender mismatch and year of transplant, the multivariate cox model on m-GRFS showed donor type, DRI risk , donor recipient sex mismatch and year of transplant to be significant predictors of m-GRFS (table 1). Patients who received a MUD had worse GRFS compared to MRD (HR 1.39, p=0.003) whereas HIDT had similar GRFS to MRD (HR 1.10, p=0.43). HIDT had better GRFS than MUD (HR 0.79, p=0.046). The adjusted 1- and 2- year m-GRFS showed donor type (MUD vs MRD), DRI, donor-recipient sex mismatch and transplant year to be associated with worse GRFS (table 2).Conclusionsm-GRFS is a useful measure of transplant success. It appears to be significantly impacted by several modifiable factors including donor type, donor-recipient sex match and also by DRI. Adjusting donor choice and early referral of patients for transplant evaluation to improve DRI can potentially overcome the negative impact of these factors. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic Impact of Delayed Platelet Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancy

Introduction: Delayed platelet engraftment (DPE) is one of important complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies suggested that DPE was risk factor for higher non-relapse mortality (NRM) and worse overall survival (OS). However, prognostic impact of DPE after allo-HSCT remains unclear. Therefore we conducted retrospective analysis to examine the clinical impact of DPE on transplant outcomes. Methods: Clinical data were collected from the clinical records of Kanagawa Cancer Center.Patients with hematological malignancies aged 16 years or older who underwent first allo-HCT between January 2002 and December 2014 were evaluated for analysis. Patients who died before day 60 after allo-HSCT were excluded. DPE was defined as non-achievement of platelet engraftment (continuous platelet counts 50×109/L or higher without transfusion) before day 60. OS, relapse and NRM were compared between patients who achieved platelet engraftment before day 60 and DPE patients, using log-rank test and Gray’s test respectively. In a multivariate analysis, the Cox proportional hazard model and Fine-Gray methods were used for OS and cumulative incidence of relapse and NRM respectively, using the following variables: age, gender, donor source, disease, disease status at allo-HSCT, donor-recipient gender mismatch, ABO mismatch, hematopoietic cell transplant comorbidity index (HCT-CI) and preemptive cytomegalovirus (CMV) therapy. Results: Of 291 patients with hematological malignancies who received first allo-HSCT (AML n = 175, ALL n = 75, others n = 41), 222 patients (76.3%) achieved platelet engraftment before day 60, 69 patients (23.7%) did not. Patients with ALL and disease low risk at allo-HSCT patients achieved early platelet engraftment. Cord blood transplantation (CBT), higher comorbidity and preemptive CMV therapy were significant risk factors for DPE. The 5-year OS and NRM for the patients who achieved platelet engraftment before day 60 were favorable, compared with the DPE group (OS; 60.3% vs. 23.2%; P < 0.001, NRM; 14.6% vs. 40.3%; P < 0.001). The 5-year relapse were comparable between both groups (30.3% vs. 37.3%; P = 0.19). Subgroup analysis stratified by donor source showed that similar results were observed both in the CBT group and in the non-CBT group. Multivariate analysis indicated that DPE was significantly associated with poorer OS (HR 3.51; 95%CI 2.40 - 5.15; P < 0.001) and higher NRM (HR 3.07; 95%CI 1.78 - 5.29; P < 0.001) after adjusting covariates. DPE had no significant impact on relapse (HR 0.95; 95%CI 0.58 - 1.56; P = 0.84). The incidence of fatal infectious disease in the DPE group was significantly higher than that in the non-DPE group (15.9% vs. 5.0%, P = 0.007), while there was no significant difference for fatal bleeding, GVHD and organ failure. Conclusions: DPE is a common complication after allo-HSCT for hematological malignancies. DPE is a useful prognostic factor for poorer OS and increased NRM. We may have to pay more attention to severe infectious disease in patients with DPE. DisclosuresNo relevant conflicts of interest to declare.