Donor-recipient Gender Matching Research Articles

The impact of donor-to-recipient gender compatibility on outcomes of haploid hematopoietic stem cell transplantation in patients with hematological malignancies

Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups (P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups (P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively (P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % (P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

The role of donor-recipient gender matching in lung transplantation: a systematic review.

Donor to recipient (D-R) matching in lung transplantation (LTx) is firstly directed by blood group (identity or compatibility), immunological status and morphological criteria. Sex matching is ignored and impact on outcome less investigated. Systematic review of English literature using PubMed (1990-2019) was performed to evaluate the potential role of D-R matching in determining long-term outcome in patients after LTx. Search terms included (LTx) AND (sex) OR (gender) OR (matching) OR (mismatch) OR (donor characteristics) and were restricted to articles' title. Only articles directly reporting LTx survival outcome according to gender match/mismatch and D-R gender combination in LTx were included. Two authors independently extracted articles using predefined data fields, including study quality indicators. MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies applied. Nine articles were analyzed and included into this study. All studies analyzed the effect of the different D-R gender combinations on survival while seven of them investigated exclusively the role of sex matching on LTx outcome. In this latter group two out of seven showed a trend towards an overall survival advantage for sex matching LTx combination. The worst survival results were reported for F to M gender combination in 3 studies and for M to F gender combination by 1 study. No differences were reported in remaining 4 studies. This systematic review suggests that sex matching and several gender combinations could play a role in determining overall survival rate after LTx. Data deriving from unbiased studies supported that matching female-female (F-F) and male-male (M-M) could improve LTx outcome while FD-MR combination should be avoided. Unfortunately, a good part of the analyzed data are affected by bias due to confounding factors. Up-to-date immunological, hormonal and morphological factors could explain the gender-based difference in LTx outcome. Further investigations should clarify their role and importance to define the effects of gender combinations on survival.

Impact of the donor-recipient gender matching on the graft survival from live donors

BackgroundSeveral factors such as recipient age, BMI, serum cratinine, and positive history of dialysis are important in predicting graft survival among kidney transplant recipients. One factor affecting the transplant outcomes is donors and recipients gender, which is usually ignored.MethodsA total of 1113 kidney transplant recipients were studied in this retrospective cohort study. Several factors were taken into account for graft survival and outcomes such as donors and recipients gender and age in addition to common recipient factors like cratinine, eGFR, BMI, and positive history of dialysis.ResultsThe most successful transplant based on donor-recipient gender was observed in male donor to male recipient, and then male donor to female recipient. In female transplant recipients, level of serum cratinine and eGFR, positive dialysis history before transplant, and low donor hemoglobin level can be considered as good prognostic factors recommended for kidney transplant survival.ConclusionsOur results suggested gender matching for kidney transplant. Only in some exceptional conditions, male donor to female recipient kidney transplant may be successful and female donors to male recipients are not suggested, especially in aged patients with the history of dialysis.

Modeling Long-Term Graft Survival With Time-Varying Covariate Effects: An Application to a Single Kidney Transplant Centre in Johannesburg, South Africa.

Objectives: Patients' characteristics that could influence graft survival may also exhibit non-constant effects over time; therefore, violating the important assumption of the Cox proportional hazard (PH) model. We describe the effects of covariates on the hazard of graft failure in the presence of long follow-ups.Study Design and Settings: We studied 915 adult patients that received kidney transplant between 1984 and 2000, using Cox PH, a variation of the Aalen additive hazard and Accelerated failure time (AFT) models. Selection of important predictors was based on the purposeful method of variable selection.Results: Out of 915 patients under study, 43% had graft failure by the end of the study. The graft survival rate is 81, 66, and 50% at 1, 5, and 10 years, respectively. Our models indicate that donor type, recipient age, donor-recipient gender match, delayed graft function, diabetes and recipient ethnicity are significant predictors of graft survival. However, only the recipient age and donor-recipient gender match exhibit constant effects in the models.Conclusion: Conclusion made about predictors of graft survival in the Cox PH model without adequate assessment of the model fit could over-estimate significant effects. The additive hazard and AFT models offer more flexibility in understanding covariates with non-constant effects on graft survival. Our results suggest that the period of follow-up in this study is long to support the proportionality assumption. Modeling graft survival at different time points may restrain the possibility of important covariates showing time-variant effects in the Cox PH model.

The impact of gender mismatching on early and late outcomes following heart transplantation.

AimsThe role of donor/recipient gender matching on the long‐term rejection process and clinical outcomes following heart transplantation (HT) outcomes is still controversial. We aim to investigate the impact of gender matching on early and long‐term outcome HT.Methods and resultsThe study population comprised 166 patients who underwent HT between 1991 and 2013 and were prospectively followed up in a tertiary referral centre. Early and late outcomes were assessed by the type of donor–recipient gender match (primary analysis: female donor–male recipient [FD–MR, n = 36] vs. male donor–male recipient [MD–MR, n = 109]). Early mortality, need for inotropic support, length of hospital stay, and major perioperative adverse events did not differ between the FD–MR and MD–MR groups. However, the FD–MR group experienced significantly higher rates of early major rejections per patient as compared with the MD–MR group (1.2 ± 1.6 vs. 0.4 ± 0.8; P = 0.001), higher rates of overall major rejections (16 vs. 5.5 per 100 person years; P < 0.05), and higher rate of cardiac allograft vasculopathy (43% vs. 20%; P = 0.01). Kaplan–Meier survival analysis showed that the cumulative probabilities of survival free of rejections and major adverse events were significantly higher in MD–MR group (P = 0.002 and 0.001, respectively). Multivariate analysis showed that FD–MR status was associated with >2.5‐fold (P = 0.03) increase in the risk for rejections and with a >3‐fold (P = 0.01) increase in the risk for major adverse events during follow‐up.ConclusionsDonor–recipient gender mismatch is a powerful independent predictor of early and late rejections and long‐term major adverse events following HT.

The Effect of Gender and Gender Match on Mortality in Pediatric Heart Transplantation

The effect of organ-recipient gender match on pediatric heart transplant mortality is unknown. We analyzed the effects of gender and donor-recipient gender matching. Based on Organ Procurement and Transplant Network data, we performed a historical cohort study in a population of 3630 heart transplant recipients less than 18 years old. We compared unadjusted and adjusted mortality by recipient gender, donor gender and between gender-matched and gender-mismatched recipients. Female recipients had decreased survival compared to male recipients (unadjusted hazard ratio [HR] 1.16, confidence interval [CI] 1.02-1.31; p = 0.020). Organ-recipient gender mismatch did not affect mortality for either male or female recipients, though gender-mismatched females had the worst survival compared to gender-matched males, who had the best survival (unadjusted HR 1.26, CI 1.07-1.49; p = 0.005). After adjustment for other risk factors affecting transplant mortality, female recipients had decreased survival compared to male recipients (HR 1.27, CI 1.12-1.44; p = 0.020) and gender matching had no effect. In conclusion, gender mismatch alone did not increase long-term mortality for pediatric heart transplant recipients. However, there may be additive effects of gender and gender matching affecting survival. There are insufficient data at this time to support that recipient and donor gender should affect heart allocation in children.

Female donor to male recipient gender discordance results in inferior graft survival: a prospective study of 1,042 liver transplants

The influence of donor-recipient gender mismatch on outcomes after liver transplantation (LT) is controversial. The aim of this study was to evaluate the effect of donor and recipient gender discordance on graft survival. All patients who underwent primary LT from 1994-2012 at a single-center were identified prospectively. Clinico-demographic data were collected at the time of LT and last follow-up. Gender match included both male donor to male recipient (MM) and female donor to female recipient (FF), while gender mismatch included female donor to male recipient (FM) and male donor to female recipient (MF). Survival curves for graft survival were generated using Kaplan-Meier method and compared by log-rank test. Unadjusted and multivariate adjusted COX regression analyzing graft survival at up to 10 years post-transplant was performed. A total of 1,042 subjects fulfilled the criteria. Graft survival in patients receiving a donor-recipient gender match was better than those receiving a gender mismatch (P = 0.047). Female-to-male transplants had the worst graft survival of all combinations (P < 0.001); this difference was maintained in multivariate regression after adjustment for recipient and donor variables (hazards ratio 2.09, P = 0.013). Female-to-male liver transplants are associated with a statistically significant poorer graft survival as compared with other donor-recipient gender groups.

Nephron Underdosing as a Risk Factor for Impaired Early Kidney Graft Function and Increased Graft Loss During the Long-Term Follow-up Period

BackgroundIt is generally accepted that kidneys procured from female donors may not perform optimally in male recipients, mostly due to their smaller size and nephron underdosing. Nowadays, conflicting results have been published regarding the detrimental effect of H-Y incompatibility on the long-term prognosis of male kidneys transplanted into female recipient. The aim of this study was an analysis of the impact of donor-recipient gender matching on early function and survival of grafts among a relatively homogenous cohort of kidney recipients. MethodsWe analyzed 477 consecutive first kidney transplants from deceased donors with longer than 3-month survival. Highly sensitized recipients and those with graft losses attributed to noncompliance were excluded from the study. Early kidney graft function was defined based on serum creatinine (Scr) concentrations at postoperative day 3 and the need for dialysis: immediate graft factors (IGF; Scr < 3mg/dL), slow graft function (Scr > 3mg/dL and no dialysis) or delayed graft function (DGF; dialysis in the first posttransplant week). ResultsThe lowest 10.7% incidence of IGF was observed among male recipients of female kidneys (F-M). For female donor, the relative risk for IGF in female recipient was 3.13 (1.35–7.26) than in male recipient. The frequencies of DGF were similar. During the 5-year follow-up, 54 grafts were lost. The risk for loss was significantly higher in the F-M group: 19.6% vs 8.8% in the three other combined groups (odds ratio = 2.54; 95 confidence interval (1.41–4.59); P = .002). ConclusionsTransplantation of the female kidney to a male recipient impairs early kidney graft function increasing the risk of graft loss over a 5-year follow-up. This phenomenon seems to be related to nephron underdosing.

Post-transplant outcomes of patients with and without hepatitis C virus infection according to donor age and gender matching

The purpose of this study was to evaluate the impact of donor age and donor-recipient gender matching on liver transplantation outcomes, focusing on differences between patients with and without hepatitis C virus (HCV) infection. This retrospective cohort study evaluated 622 liver transplantation recipients. HCV (n=164) and non-HCV (n=458) patients were subdivided by donor age (≤ 30, 31-50, and >50 years) and donor-recipient gender configurations. Five-year patient survival (PS) and graft survival (GS) were set as outcome measures. Five-year PS was 83.1% for HCV-positive and 81.6% for HCV-negative patients (p=0.614), with the corresponding GS rates of 81.2% and 79.3% (p=0.538), respectively. In HCV patients, transplantations from donors older than 50 years were associated with lower PS (p=0.035) and GS (p=0.006) than those from donors aged 31-50 years. This difference was not observed among non-HCV recipients (PS, p=0.994; GS, p=0.878). Regarding donor-recipient gender configurations, outcomes were similar in HCV (PS, p=0.751; GS, p=0.592) and non-HCV patients (PS, p=0.217; GS, p=0.249), except for a tendency toward lower PS for male-to-female transplantations than female-to-female transplantations in non-HCV patients (p=0.064). Outcomes of HCV patients were superior to those of non-HCV patients after transplantation from donors aged 31-50 years (PS, p=0.080; GS, p=0.026). Avoiding the transplantation of grafts from donors aged over 50 years to patients with HCV infection might improve the general outcomes of liver transplantation programs. There is no specific rationale for gender matching with respect to HCV status.

Lower Transplant-Related Mortality and Improved Survival for Patients with AML in First CR Receiving BuCy Compared to Cy/TBI As Myeloablative Preparation for Allogeneic Transplantation: A Report From the Center for International Blood and Marrow Transplant Research (CIBMTR)

AbstractAbstract 217 Background:The most widely used myeloablative preparative regimens for allogeneic hematopoietic cell transplantation (HCT) in myeloid malignancies consist of cyclophosphamide in combination with total body irradiation (Cy/TBI) or with orally or intravenously (IV) administered busulfan (BuCy). The relative advantages and shortcomings of these regimens have been debated for more than 25 years, but definitive conclusions regarding their comparative effectiveness and limitations are lacking. Patients and Methods:Using data from the CIBMTR we retrospectively analyzed all patients who underwent first allo-HCT from a human leukocyte antigen (HLA)-matched sibling or adult unrelated donor from 2000 through 2006 for Chronic Myeloid Leukemia in first chronic phase or Acute Myeloid Leukemia (AML) in first complete remission following preparation with Cy/TBI or BuCy. Information regarding Bu pharmacokinetics was not collected during the period of study. Results:2284 patients aged 2 to 64 (median 34) years are included: 997 patients received Cy/TBI, 890 oral BuCy and 397 IV BuCy. In univariate analysis of the entire cohort, there were no significant differences in neutrophil recovery, chronic graft versus host disease (GVHD) or relapse between the groups. Platelet recovery occurred more rapidly (P=.002), grades 2–4 acute GVHD and transplant-related mortality (TRM) at 3 years were less frequent, and leukemia-free survival (LFS) and overall survival (OS) at 3 years were superior following IV or oral Bu compared to TBI (P<.001 for all comparisons).In multivariate analysis (adjusted for patient-related (age, gender, and Karnofsky performance score at transplant), disease-related (disease, time from diagnosis to transplant, and cytogenetic risk groups for AML), and HCT-related variables (donor-recipient gender and CMV match, donor and graft type, year of transplant, GVHD prophylaxis, and planned use of growth factors post-HCT)), the lower incidence of grades 2–4 acute GVHD with oral Bu vs. TBI (relative risk [RR] 0.85; 95% confidence intervals [CI] 0.73–0.99), and IV Bu vs. TBI (RR 0.76; 95% CI 0.64–0.91) remained significant. The incidences of chronic GVHD, TRM, and relapse within the first year post HCT did not differ between groups, however, relapse beyond the first year occurred significantly less frequently in those receiving IV(RR 0.39; 95% CI 0.21–0.73), but not oral Bu (RR 1.36; 95% CI 0.99–1.86) compared to TBI. OS was similar among the three groups. However, LFS was superior in patients receiving IV (RR 0.78; 95% CI 0.65–0.93), but not oral Bu (RR 0.97; 95% CI 0.84–1.12), compared to TBI (Figures 1).Multivariate analysis (adjusted for same set of variables listed above) restricted to AML patients only (median age 35, range 2–64 years) revealed less TRM in those receiving oral (n=473; RR 0.75; 95% CI 0.57–0.98) or IV (n=272; RR 0.67; 95% CI 0.49–0.92) Bu compared to those receiving TBI (n=646). Relapse within first year post HCT did not differ between the groups, however, relapse beyond first year occurred significantly less frequently in patients receiving IV (RR 0.26; 95% CI 0.10–0.65), but not oral Bu (RR 1.26; 95% CI 0.84–1.90), compared to TBI. LFS was superior in AML patients receiving IV (RR 0.74; 95% CI 0.59–0.92), but not oral Bu (RR 0.88; 95% CI 0.74–1.06) compared to TBI. OS was superior among AML patients receiving oral (RR 0.80; 95% CI 0.67–0.97) or IV (RR 0.73; 95% CI 0.58–0.91) Bu compared to TBI. Survival was not significantly different between oral and IV Bu (RR 1.10; 95% CI 0.86–1.42) patients (Figures 2). Conclusions:This large retrospective comparison of preparative regimens by the CIBMTR demonstrates a lower incidence of grades 2–4 acute GVHD in patients receiving Cy plus oral or IV Bu compared to TBI. Among the entire cohort, late relapses occurred less often and LFS was superior in patients receiving IV, but not oral Bu, compared with TBI.Among nearly 1400 AML patients, there were fewer late relapses and LFS was superior following IV, but not oral, Bu compared to TBI. TRM occurred less frequently and survival was superior in patients receiving either oral or IV Bu compared to TBI. This large multi-institutional retrospective analysis demonstrates that in patients with AML in first CR, in combination with Cy, Bu is associated with a significantly lower incidence of TRM and superior survival than TBI. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Influence of Gender Donor-Recipient Combinations on Survival After Human Lung Transplantation

Background In the current practice of lung transplantation, donor and recipient genders are neither directly considered nor matched. However, some data have suggested a possible effect of gender combinations on survival following lung transplantation. Methods A total of 249 adult lung transplant recipients at a single center between February 1988 and December 2008, were analyzed retrospectively for donor-recipient gender matching. We compared the mortality by calculating one-term survival rates after transplantation using the Kaplan-Meier method with comparisons using the log-rank (Mantel-Cox) test. Statistical significance of the mean effects of size matching was assessed by paired Student t tests and Wilcoxon signed rank tests. Results Kaplan-Meier survival analysis shown that male compared to female recipients did not have an effect on outcomes after lung transplantation at 5 years ( P = .5379), 10 years ( P = .107), 15 years ( P = .0841), 20 years ( P = .0711). No effect of gender on lung transplantation outcomes was observed with donor-recipient gender mismatches at 5 years ( P = .1804), 10 years ( P = .1457), 15 years ( P = .0731), or 20 years ( P = .0629). Similarly, no differences were observed for each gender combination. The degree of size matching was defined as the ratio of donor-to-recipient predicted total lung capacity. The ratios were similar for the donor-recipient gender match and significantly different for the donor-recipient gender mismatch. Conclusions These analyses suggested that gender was not a significant independent risk factor affecting survival after lung transplantation. Size mismatch caused by gender mismatch did not increase mortality.

Abstract 16802: Gender Match Does Not confer Survival Advantage in Pediatric Heart Transplantion

Background: In adult heart transplant recipients, a survival advantage for male recipients with donor-recipient gender match has been shown. We determined if similar effects of recipient gender, donor gender, and donor-recipient mismatch exist in pediatric heart transplantation. Methods: We reviewed the United Network for Organ Sharing (UNOS) database for 3630 first time heart transplant recipients younger than age eighteen years transplanted between January 1994 and May 2008. We determined mortality rates based on recipient gender, donor gender, and donor recipient gender match with and without adjustment for known risk factors, including presence of congenital heart disease, assist device, race, donor or recipient age, era, elevated bilirubin or creatinine, mechanical ventilation, and dialysis. Results: Female recipients (F) had increased mortality compared to male recipients (M) with adjusted hazard ratio (HR) = 1.27 (1.12-1.44, p &lt; .001). Donor gender had no effect on mortality. Gender mismatch conferred no survival disadvantage for male recipients with adjusted HR = 1.09 (0.92-1.29, p= .330) nor female recipients with HR= 1.12 (0.93-1.36, p=0.330). The largest survival effect was between M to M and M to F groups (HR=1.38; 1.17-1.63, p&lt; .001). However, 5 year conditional survival was similar between all groups (M to M, F to F, M to F, F to M) (log rank p =.1077 for 30 day and p=.0595 for 1 year survivors). Conclusion: In pediatric heart transplant recipients, unlike adult patients, gender match does not confer survival advantage. Female recipients have increased mortality compared to male recipients. Gender specific recipient risk factors post transplant should be investigated.

346: The Impact of Donor-Recipient Gender Matching on Survival and Rejection after Cardiac Transplantation

346: The Impact of Donor-Recipient Gender Matching on Survival and Rejection after Cardiac Transplantation

Abstract 5852: The Impact of Donor-Recipient Gender Pairing On Survival Following Orthotopic Heart Transplantation - An Analysis Of Over 18,000 Matches

Introduction : Single institution series have suggested that donor-recipient gender matching may be an important factor influencing survival following orthotopic heart transplantation (OHT). The United Network for Organ Sharing (UNOS) database provides a unique and novel opportunity to address this issue by examining outcomes based on gender pairing for a large cohort of OHT patients. Methods : We retrospectively reviewed the UNOS dataset to identify 18,240 patients receiving first time OHT between the years 1998 and 2007. Stratification was by both donor and recipient gender so that 4 separate groups were created (male donor with male recipient, female donor with male recipient, male donor with female recipient, and female donor with female recipient). The primary endpoint of all cause mortality was compared between groups using a Cox proportional hazard regression model. Secondary outcomes (thirty day and one year mortality and rejection during the first year) were examined with multiple logistic regression. Post transplant survival was modeled via the Kaplan Meier method. Results : Of 18,240 patients, 12,951 (71%) were matched by gender to their donor (77% for male recipients, n= 10,750 and 51% for female recipients n= 2,201). A total of 4,543 patients died during the study period (25%). Donor-recipient gender matching resulted in a reduction in the risk of adjusted cumulative mortality (Hz ratio 0.86 [0.78–0.95], p= 0.003) and the greatest risk for cumulative mortality occurred when pairing a male donor with a female recipient (Hz ratio 1.2 [1.04–1.37], p= 0.01). Thirty day and one year mortality were also significantly decreased by gender pairing (OR 0.75 [0.61–0.95], p= 0.02 for 30 day mortality, and OR 0.8 [0.68–0.93], p= 0.005 for one year mortality). Gender pairing resulted in a 13% decrease in the risk of graft rejection within the first year (OR 0.87 [0.79–0.98], p= 0.02]. Kaplan Meier survival modeling revealed that the greatest cumulative survival occurred when a male recipient received an organ from a male donor (Figure) Conclusions : The UNOS dataset has provided a large sample examining donor recipient gender pairing in OHT. Recipients who receive organs for same sex donors have significantly improved short and long term survival.

Effect of Bone Marrow Hypoplasia Secondary to Reinduction Therapy for Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) on Outcomes after Blood and Marrow Transplantation (BMT).

Refractory AML and MDS are difficult diseases to manage, even with allogeneic BMT, due to recurrent disease. In an attempt to cytoreduce prior to BMT, but also avoid the toxicities associated with multiple reinduction attempts, we altered our treatment practice to offer allogeneic BMT while the patient is hypoplastic after reinduction therapy. We retrospectively reviewed 47 consecutive patients (22 males, 25 females; median age 47 years, range 6–68,) with AML (n=36) or MDS (n=11) who received a first related (n=23) or unrelated (n=24) allogeneic BMT between 4/1/2003 and 3/31/2006 at Roswell Park Cancer Institute to compare outcomes by pre-BMT disease status. Bone marrow hypoplasia post-reinduction therapy was defined as a particulate biopsy with <20% cellularity and <5% myeloblasts within 1 to 4 weeks before BMT. Fourteen patients met this definition and were compared to 33 patients who had untreated MDS or AML in CR (n=25) or were relapsed/primary induction failure (n=8). We analyzed the association of the following characteristics with hypoplasia post-reinduction/pre-BMT: diagnosis, conditioning regimen, donor relation, HLA-matching, KPS, stem cell source, donor-recipient gender matching, age, ejection fraction, DLCO, FEV1, and time from diagnosis to BMT. In the univariate analysis, KPS was the only significant factor associated with hypoplastic status at time of BMT with all hypoplastic patients having a KPS ≤80 pre-BMT (p=0.002). Patients who were transplanted while hypoplastic had shorter overall survival (OS) compared to non-hypoplastic patients (p=0.0088) and also had a trend toward shorter leukemia free survival (LFS) (p=0.0936). Additionally, patients with active disease at BMT had poorer OS than patients who were untreated or in CR, and patients who were hypoplastic fared worse than those with active disease (1 year OS was 54% vs. 69% vs. 30%; p=0.027). Multivariate analysis of OS used a Cox proportional hazards model with forward stepwise selection conditional on the likelihood ratio with p<0.05 to enter and p>0.10 to remove each factor from the model. Since KPS correlated with hypoplastic status, both factors could not be added into the model simultaneously. Factors that were considered in the first model: KPS (≥90 vs. ≤80), conditioning regimen (FluMel vs. BuC vs. CT vs. FluC), donor (related vs. unrelated), age at BMT (continuous), and FEV1 (continuous). KPS was the only significant predictor of OS (RR=20.5; 95% confidence interval 2.7, 156; p=0.004). Substituting hypoplastic (yes vs. no) for KPS in the model yielded hypoplastic as the only significant factor (RR=3.06; 95% CI 1.3, 7.38; p=0.013). This study demonstrates that patients transplanted with bone marrow hypoplastia secondary to reinduction therapy have a compromised performance status, but that a low KPS is a stronger predictor of poor LFS and OS. Reducing the intensity of the reinduction regimen may increase performance status at BMT and improve overall outcome post-transplant.

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) - EBMT Risk Score Evaluation for Chronic Myeloid Leukemia in Brazil.

This is a retrospective analysis of 1084 patients who received an allogeneic HSCT in 10 Brazilian Centers, from February 1983 to March 2003, aiming to validate the EBMT risk score. Data from transplanted patients and donors regarding patients age, disease stage at transplantation, HLA full-match sibling donor or full-match unrelated donors, donor-recipient gender match and the interval from diagnosis to transplantation, were used as variables to calculate the EBMT risk score. This score was analyzed using Cox Proportional Hazards Model. The OS, DFS, TRM and relapse were analyzed using Kaplan-Meier and cumulative incidence, whenever appropriate. In all there were 647 (60%) males and 437 (40%) females, the median age was 32 years old (range 1 – 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1025 (95%) received HLA full-match sibling transplant and only 59 (5%) received an unrelated transplant. Female donor to male recipient occurred in 283 (26%) transplants. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The OS, DFS, TRM and, relapse were 49%, 50%, 45%, 25%, respectively. The risk score 0–1 occurred in 179 (17%), score 2 in 397 (37%), score 3 in 345 (32%), score 4 in 135 (12%), and score 5–6 in 28 (2%). The risk scores 0–1 and 2 did not show any difference in terms of OS (58% and 55%, respectively) but they were significantly better than scores 3 or more (score 3 – 44%, 4 – 36 % and, 5-6 - 27%, respectively) (P<0.001). DFS and TRM beyond score 3 were 46%, 49%, respectively and the relapse rate beyond score 5–6 was 77%. Disease status had a negative impact on all outcomes (OS, DFS, TRM, and relapse). OS for female donor - male recipient was 40% compared to 52% for the other patients (P=0.004). DFS and TRM were significant for disease phase and female donor-male recipient (P<0.001 and P<0.003, respectively). In our experience, age and interval from diagnosis and transplant did not show any difference in terms of OS, DFS, TRM, and relapse rate. Our results confirm the usefulness of the EBMT risk score for point-decision in the Imatinib era.

Donor—recipient gender mismatch in lung transplantation: Impact on obliterative bronchiolitis and survival

Background Because of the shortage of donor lungs, liberalization of donor selection criteria in terms of age, gas exchange, and smoking history has been proposed. Methods We evaluated a single-institution population of lung transplant recipients ( n = 98) for donor—recipient gender matching. We measured overall survival, time to acute allograft rejection, and time to development of obliterative bronchiolitis (OB). Results We found significant improvement in overall survival for gender-mismatched donor and recipient pairs ( p = 0.078) and a significantly shorter OB-free period for male donor and female recipient pairs ( p = 0.017). Conclusion These findings suggest that donor organ allocation based on gender may affect long-term survival and other outcomes after lung transplantation.

CAN SERUM CREATININE IN THE FIRST YEAR AFTER TRANSPLANT PREDICT LONG-TERM RENAL TRANSPLANT OUTCOME?

P349 Aims: As short-term renal transplant survival continues to improve, with known risk factors having a diminishing effect, attention is increasingly focussing on alternative measures of outcome such as renal function. This study explores the relationship between renal function in the first year after transplant and long-term kidney transplant survival in the UK. Methods: Cadaveric heartbeating donor kidney only transplants in adult patients in the UK between 1983 and 1987 were analysed. Transplants failing in the first year were excluded. For 75% of the remaining cohort, both 3 and 12-month serum creatinine measures were recorded on the UK’s national transplant database. Transplant survival analysis (death with function counted as a failure) considered the influence on ten-year outcome of 3 and 12-month serum creatinine; the change between 3 and 12 month serum creatinine (Δ creatinine) and other potential risk factors recorded. Data were available for 2766 transplants with 97% 10-year follow-up including 17% regrafts, which were analysed separately. Results: Analysis of first transplants showed a highly statistically significant association between ten-year transplant survival and 12-month creatinine, Δ creatinine and an interaction of the two (p<0.0001). Unadjusted 10-year transplant survival estimates ranged from 62% (95% confidence interval (CI) 58-65%) for transplants with 12-month serum creatinine <120 μmol/l to 13% (95% CI 9-18%) for those with 12-month creatinine >= 265 μmol/l. There was a negative association between outcome and Δ creatinine, which was greatest for those with poor function at 12-months. Other factors adjusted for were recipient age (p<0.0001), blood group (p<0.001) and HLA match (p<0.1). Univariately, donor age and donor-recipient gender match were significant, but these effects disappeared with the introduction of measures of post-transplant renal function. Analysis of regrafts and of graft (death-censored) survival both showed comparable results. The relevance of findings to more recent data was validated by analysis of 3-year outcome of a recent cohort. Conclusions: For transplants functioning after the first post-operative year, 12-month serum creatinine and Δ creatinine were highly predictive of 10-year transplant survival. There was a 49% survival difference at 10-years post-transplant between the group with the poorest renal function at one year and the group with the best function.

Gender matching and outcome after pediatric liver transplantation.

Gender is not a selection criterion for orthotopic liver transplantation (OLT), and reports in adults have shown a less favorable outcome for male recipients of female organs; the only pediatric study did not support this finding. The aim of the present study was to assess the impact of donor and recipient gender on graft and patient survival rates after pediatric OLT. We have reviewed retrospectively 137 children (male=63; median age: 3.4 years; range: 14 days to 15 years) undergoing primary OLT from January 1991 to June 1996. These children were divided into donor-recipient gender match (M; n=64) and nonmatch (NM; n=73) groups and then classified into female to female (FF; n=30), female to male (FM; n=29), male to female (MF; n=44), and male to male (MM; n=34) subgroups. The M group had better graft and patient survival rates at both 1- and 5-year follow-up compared with the NM group (P<0.01). Graft and patient survival rates were different among gender subgroups (P<0.04). Graft and patient survival rates in the FM group were poorer than in the MM subgroup at both 1 and 5 years (P<0.03, P<0.01). The FM group had a higher incidence of early complications than the MM (P<0.01) group, with 50% and 33% of graft losses, respectively, related to the complications. To minimize the influence of hormonal factors, we have analyzed separately the patients younger than 12 and 10 years who had similar findings. Graft and patient survival rates after pediatric OLT are worse in gender mismatch groups, particularly for male recipients of female organs. Early complications play a role in the decreased survival rates.

The Role of Gender in Heart Transplantation

Background. The effect of donor and recipient gender on the outcome of heart transplantation (HT) remains uncertain. Methods. One hundred seventy-four patients who underwent HT were divided into four groups according to donor and recipient gender. Group A consisted of 81 men who received male donor hearts, group B of 18 women who received female donor hearts, group C of 21 women who received male donor hearts, and group D of 54 men who received female donor hearts. All patients were treated by the same group of surgeons according to standard HT protocols. Comparisons were made between groups with regard to short- and long-term outcomes. Results. Donor gender and recipient gender did not affect outcomes significantly. Overall, donor-recipient gender mismatching significantly increased the number of rejection episodes and reduced creatinine clearance, survival, and censored survival in the first year after HT ( p < 0.05). More specifically, among female recipients, donor-recipient gender mismatching significantly increased the number of rejection episodes and decreased creatinine clearance in the first year after HT ( p < 0.05); among male recipients, donor-recipient gender mismatching significantly reduced 1-year survival and censored survival to date after HT ( p < 0.05). Conclusions. Donor-recipient gender matching plays a significant role in determining HT outcomes.