Donor-recipient Gender Combinations Research Articles

Impact of age and gender matching on long-term graft function and actual graft survival in live-related renal transplantation: Retrospective study from Sindh Institute of Urology and transplantation, Pakistan.

In renal transplantation, donor and allograft age are known to have an important influence on the outcome of the graft, reflecting functional renal mass. We evaluated the impact of gender and age matching in living-donor renal transplantation on long-term graft survival and actual graft function over five years from the day of transplantation. We retrospectively analyzed 500 primary live-related donor renal transplants performed from August 2007 to December 2008 at Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Donors and recipients were divided into two age groups [young (YD) and elderly (ER)] with 40 years as cutoff line. Four donor recipient groups according to age match and age mismatch: YD/YR - ED/ER - YD/ER - ED/YR and four groups according to donor-recipient gender combinations: male recipients of male donors (MR/MD)-female recipients of male donors (FR/MD)-female recipients of female donors (FR/FD)-male recipients of female donors MR/FD) were studied. Serum creatinine was used to assess graft function after transplantation. The Kaplan-Meier method with the log-rank test was used to assess actual graft survival at five years. Actual graft function of four study groups based on age difference had no statistically significant difference at five years (P = 0.094). Regarding the actual graft survival, the best results were seen in young donor to elderly recipient group as compared to all other age combination groups. At five-year post-transplant, MD/MR had significantly better graft function than MR/FD and FR/MD had significantly better graft function than FD/FR and FD/MR. The actual graft survival was best in male-to-male (86%) compared to the lowest in female-to-female transplants (75%). The graft function at five years was better in elderly recipients of young donor kidneys. The actual graft survival was influenced positively by young donor age and negatively influenced by pre-transplant hepatitis C positivity of recipients.

Deceased-donor acute kidney injury is not associated with kidney allograft failure

Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate≤ 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.

European Group for Blood and Marrow Transplantation Risk Score Predicts the Outcome of Patients with Acute Leukemia Receiving Single Umbilical Cord Blood Transplantation

The European Group for Blood and Marrow Transplantation (EBMT) risk score has been implemented as an important tool to predict patient outcomes after allogeneic hematopoietic stem cell transplantation. However, to our knowledge, this score has never been applied in cases of single umbilical cord blood transplantation (sUCBT). We retrospectively analyzed 207 consecutive patients with acute leukemia who received sUCBT at our center between February 2011 and December 2015. The probabilities of 3-year overall survival (OS) and leukemia-free survival (LFS) of the entire cohort were 65.0% and 59.8%, respectively, whereas the cumulative incidences of 3-year nonrelapse mortality (NRM) and relapse rate were 19.5% and 20.3%, respectively. In the univariate analysis, a higher EBMT risk score was associated with worse OS and LFS and higher NRM and relapse rate, ranging from 81.7%, 75.9%, 7.3%, and 15.3%, respectively, for patients with a score of 1 to 43.8%, 44.3%, 31.7%, and 23.9%, respectively, for patients with scores of 4 to 6. Hazard ratios of OS, LFS, and NRM all steadily increased for each additional score point. Importantly, the prognostic value of the EBMT risk score on OS, LFS, NRM, and relapse was maintained in the multivariate analysis. Moreover, considering the univariate analysis results of donor–recipient gender and mismatched allele-level HLA-A, -B, -C, and -DRB1 loci on patient outcomes and the fairly strong interaction between time from diagnosis to sUCBT and disease status, we developed a modified sUCBT-EBMT risk score by using degrees of 8-allele HLA match instead of donor type, donor–recipient gender combination, and time from diagnosis to sUCBT, and found that the modified score could also be used as a predictor for patient outcomes after sUCBT. The EBMT risk score is a good predictor of outcomes of patients with leukemia after sUCBT. The modified sUCBT-EBMT risk score can also be used as a pretransplant risk assessment, but this metric still requires further evaluation with a larger cohort.

Lung transplantation and gender effects on survival of recipients with cystic fibrosis

The overall life expectancy of women with cystic fibrosis (CF) is shorter compared with men with CF without accounting for lung transplant recipients. However, it is unclear how donor and recipient gender impact long-term outcomes in patients with CF who undergo lung transplantation. The purpose of this study was to determine if the gender disadvantage seen in women with CF before transplant continues to exist after lung transplant and if this is impacted by donor gender. Patients with CF entered in the International Society for Heart and Lung Transplantation registry who were at least 18 years old and received a lung transplant between January 2000 and December 2012 were included and divided into groups based on donor-recipient gender combinations. Kaplan-Meier curves were used to determine post-transplant rates of overall survival and bronchiolitis obliterans syndrome (BOS)-free survival. The analysis included 4,971 patients undergoing lung transplantation for CF. There was no significant difference in BOS-free survival or overall survival rates between genders or between gender-matched vs gender-mismatched recipients after lung transplantation. However, women with CF underwent transplantation at a younger age and died at an earlier overall age than men with CF. Survival after lung transplantation and time to the development of BOS did not differ based on gender or donor-recipient gender combination. However, women with CF continue to demonstrate a poorer overall life expectancy, as their pre-transplant disadvantage could not be overcome after lung transplantation.

Reduced intensity conditioning and oral care measures prevent oral mucositis and reduces days of hospitalization in allogeneic stem cell transplantation recipients

Oral mucositis (OM) is a side effect of intensive chemotherapy and radiation and has been reported to affect 75-100% of hematopoietic stem cell transplantation (HSCT) recipients. The purpose of this study was to compare the incidence of OM in patients conditioned with myeloablative conditioning (MAC) to reduced-intensity conditioning (RIC) and to determine the effect of a new oral care protocol. The study involved 171 HSCT recipients, with hematological malignancies transplanted between 2007 and 2011. Median age of the patients was 50 years (range 12-71). Ninety-nine (58%) received RIC and 72 received MAC. Clinical features of OM were recorded from day -3 before to day +25 after HSCT using the World Health Organization (WHO) scoring system and the oral mucositis assessment score (OMAS). Overall, 87% of the patients developed OM of any severity, which peaked on days 10-11. The mean WHO score was 1.7. In multivariate analysis, the severity of OM was associated with MAC (relative hazard (RH) 1.57, 95% confidence interval (CI) 1.37-1.80, p < 0.001), all donor-recipient gender combinations except female-to-male (RH = 1.26, 95% CI 1.10-1.4, p = 0.001), and early year of HSCT (RH = 0.84, 95%CI 0.7-0.96, p = 0.013). There was a correlation between long hospitalization and OM (day 15, r = 0.31, p < 0.001). There was a good correlation between the WHO and OMAS scoring systems for OM (r = 0.74, p < 0.001). Oral mucositis was reduced in patients treated with RIC and in patients treated during recent years, when oral care was intensified. Increased scores of OM prolonged hospitalization.

Female Donor Allografts Have a Higher CD3 Content Than Male Donor Allografts: Potential Impact On Transplantation Outcomes in Male Recipients

AbstractAbstract 587 Introduction:In allogeneic stem cell transplantation, the donor-recipient gender combination plays a role in outcome. In large retrospective registry studies, acute and chronic graft–versus -host-disease (GVHD) were more frequent and treatment related mortality (TRM) higher in male recipients with a female donor than in other donor-recipient gender combinations. These were attributed to female donor T cells specific for male minor histocompatibility antigens encoded by Y-chromosome genes. We speculated that quantitative rather than qualitative cell composition differences between grafts harvested from male and female donors may have a role in the difference in patients’ outcome. Methods:We investigated the CD34 and CD3 cell composition of grafts derived from G-CSF mobilized peripheral blood grafts (male donors, n=408, female donors, n=217) and their relation to various transplantation outcomes in 641 allogeneic transplantation recipients from three tertiary medical centers between the years 2001 and 2012. The median age of this cohort was 52 years (range, 17–76); 44% were in CR/PR at transplantation. The donor was an HLA-matched sibling in 57% and 4% had a 1 allele mismatched donor. Cord blood and haplo-identical transplantations were not included in the analysis. Myeloablative conditioning was used in 59% of the transplants. CD34 and CD3 graft composition were measured by multicolor flow cytometry analyses and expressed as infused cells/kg of actual recipient weight. Cox regression analysis was used to model the impact of CD34 and CD3 levels on time-to-event endpoints. CD34 and CD3 doses were divided according to quartiles. Results:Male and female donor grafts differed significantly in CD34 and CD3 cell content. Compared with male donors, grafts derived from females had a higher mean CD3/kg cell content (4.0 ±1.9*108 vs. 3.3±1.6*108, p<0.001), a lower mean CD34/kg cell content (6.9±2.3*106 vs. 8.1±2.3*106, p<0.001) and a higher CD3/CD34 ratio (66.8 ±47.9 vs. 45.7±30.5, p<0.001).Univariate analysis for grade 2–4 acute GVHD identified female donor to male recipient, unrelated donor and allele mismatch as factors associated with a higher risk for GVHD. However when adjusted to CD3 dose, only grafts derived from unrelated donors (p=.04) and allele mismatch (p=.006) remained statistically significant.Among all patients, there was no association between higher CD34/kg or CD3/kg graft counts and the incidence of acute GVHD, chronic GVHD, relapse rate, non-relapse mortality and overall survival.However, among male recipients given female allografts, the incidence of grade 3–4 acute GVHD in patients given higher doses of CD3 in the upper quartile was statistically significantly higher than patients receiving lower doses of CD3, namely 39% vs. 16% (p=.04), Figure. Differences were more prominent in patients given allografts from unrelated females. The incidence of grade 2–4 acute GVHD in patients given higher doses of CD3 in the upper quartile was 65%, and 50% in the 3 lower quartiles (p=.27). Of note, patients in the upper quartile had a higher non-relapse mortality (58% vs. 33% p=.05), a higher incidence of chronic GVHD (89% vs. 47%, p=.03) and a lower disease relapse rate (23% vs. 40%, p=.42). Overall survival was comparable.These correlations were not observed when other donor-recipient gender combinations were analyzed. Conclusion:Male and female donor grafts differ significantly in CD34 and CD3 cell composition. Grafts derived from female donors have a higher mean CD3 and a lower mean CD34 cell content compared with grafts derived from male donors.CD3 dose independently impacts transplantation outcomes in male patients given female allografts, explaining some of the adverse outcomes in this subgroup compared with other donor-recipient gender combinations.Finally, in this subgroup, escalation of CD3 dose in patients with high risk diseases and de-escalation of CD3 dose in patients with low risk diseases should be considered. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Frequency and Intensity of Antibody Responses to Antigens Encoded by KDM5D (SMCY) and Other H-Y Genes After Allogeneic Hematopoietic Cell Transplantation,

Abstract 4028Male recipients of female hematopoietic cell grafts (F->M HCT), when compared with other donor/recipient gender combinations, face an increased risk for both acute and chronic graft-versus-host disease (GVHD), but also have a significantly decreased risk of posttransplant relapse. F->M HCT is characterized at the cellular level by female donor T cell responses against male-specific minor histocompatibility (H-Y) antigens, which can contribute to both GVHD and graft-versus-leukemia (GVL) activity. Data from both murine models and clinical studies of allogeneic HCT demonstrate that the protein product of the Y chromosome gene KDM5D (previously known as SMCY) is one of the major targets of H-Y-specific T cell responses. CD8+ T cell responses against KDM5D peptides have been associated with GVHD and GVL in male recipients of female grafts, and with rejection of male grafts by female recipients.A subset of Y chromosome-encoded proteins, including several that are targets for CD8+ and CD4+ T cell responses after F->M HCT, are also the targets of antibody responses in this setting (Miklos et al., Blood 2005; 105:2973). Antibody responses to the protein products of DDX3Y and UTY, in particular, have been detected in up to 50% of F->M HCT recipients. Moreover, antibody responses to these Y chromosome gene products have been associated with the development of chronic GVHD as well as the maintenance of remission. T cell responses to KDM5D in F->M HCT recipients have been extensively studied, but KDM5D-reactive antibody responses have not been thoroughly evaluated. We hypothesized that KDM5D -reactive antibodies would also develop in a significant fraction of F->M HCT recipients, and undertook an exploratory study to define the frequency and intensity of antibody responses to KDM5D in both allogeneic HCT patients and healthy adult male and female control subjects.Plasma samples were obtained from 39 male HCT patients with female donors, 16 HCT patients with other donor/recipient gender combinations, 12 healthy female controls, and 9 healthy male controls, and assessed for IgG responses against an array of 84 different protein targets by ELISA. The target panel included partial (SMCY and UTY) or whole (DDX3Y, ZFY RPS4Y, and E1F1AY) recombinant H-Y proteins and their X chromosome-encoded homologues that had been expressed in and purified from E. coli, as well as synthetic overlapping peptides of length 15–21 residues derived from the KDM5D and DDX3Y protein sequences or from their X chromosome-encoded homologues KDM5C (SMCX) and DDX3X. Of the 55 samples acquired from HCT recipients, 49 came from recipients who had previously been diagnosed with cGVHD and were receiving immunosuppressive therapy.Reactivity with KDM5D-derived peptides or recombinant KDM5D protein fragments was observed in HCT recipients of all four donor-recipient gender combinations and also in some healthy control males and females. Amongst male patients with female donors, 7 of 39 (18%) samples were reactive with more than 3 KDM5D peptides, and 2 of 16 (13%) samples from patients with other donor/recipient gender combinations were reactive with 3 or more KDM5D peptides. Significant differences in the frequency of reactivity with individual peptides were observed, with a high frequency of responses to peptides corresponding to sequences within the interval KDM5D281–375, a region of the protein where there is significant nonidentity with the sequence of its X chromosome-encoded homologue KDM5C. This region also contains the sequence FIDSYICQV, which comprises the epitope recognized by CD8+ HLA-A*0201-restricted T cell clones that have frequently been isolated from HLA-A*0201+ F->M HCT recipients and have been associated with both GVHD and GVL. Antibody reactivity to KDM5D was correlated with reactivity to several DDX3Y-derived peptides previously shown to be the targets of antibody responses in F->M HCT recipients, but weakly associated with responses to UTY protein fragments, which were observed in 11 of 39 (28%) F->M patients and 1 of 16 (6%) patients with other donor/recipient gender combinations. These results suggest that KDM5D is a frequent target of posttransplant antibody responses in allogeneic HCT recipients. Current studies are evaluating in a larger cohort of patients the relationship of KDM5D-reactive antibody responses to H-Y-specific T cell responses and to the development of acute and chronic GVHD. Disclosures:No relevant conflicts of interest to declare.

The EBMT risk score

The European Group for Blood and Marrow Transplantation (EBMT) risk score provides a simple tool to assess instantly chances and risks of hematopoietic SCT(HSCT) for an individual patient pre-transplant. Five factors, age of the patient, stage of the disease, time from diagnosis, donor type and donor recipient gender combination augment risk for an individual patient with increasing score from 0 as best to 7 as worst in an additive way. The score holds for all acquired hematological disorders, for allogeneic and autologous HSCT (score 0-5), is independent of the HSCT technology and is valid for standard or reduced intensity conditioning. Survival is uniformly worse for older patients, transplanted in advanced disease stage after a long-time interval and with a mismatched donor than for younger patients, transplanted soon in early stage with a well matched donor. Additional risk factors such as performance score, CMV serostatus or cytokine polymorphisms improve prediction but to different extents for low or high-risk patients. Comparative assessment of disease risk and global pre-transplant risk should guide decisions for each patient with his/her specific disease between HSCT and a non-transplant approach and replace the traditional 'donor vs no donor' with such a risk-adapted individualized strategy.

Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

Poor-Risk Acute Leukemia Patients with An EBMT Low-Risk Score and An 8/8 Matched Unrelated Donor Show Excellent Survival After Hematopoietic Stem Cell Transplantation.

Abstract 1196Poster Board I-218 Introduction:Allogeneic hematopoietic stem cell transplantation (alloSCT) from volunteer unrelated donors (URD) may be associated with a higher non-relapse mortality (NRM) and worse outcome as compared to alloSCT using HLA-identical sibling donors. However, many parameters next to donor type define NRM. The impact on outcome of allele-matching for HLA-A, -B, -C and -DRB1 between donor and recipient has clearly been demonstrated. The prognostic impact of the EBMT risk score, that takes into account age, stage of disease, time from diagnosis to transplantation, donor type and donor-recipient gender combination, has recently been validated in a variety of hematological malignancies including acute leukemia and myelodysplastic syndrome (MDS). We evaluated the relative prognostic value of high-resolution HLA matching and the EBMT risk score for patients with poor-risk acute leukemia and MDS who received an URD transplant. Patients and methods:Between 1987 and 2006, 327 patients (≥16y) with poor-risk acute leukemia and MDS underwent URD alloSCT in the Netherlands. Patients were in 1st complete remission (CR1, n=129), 2nd CR (CR2, n=91), beyond CR2 or not in remission (n=107). The leukemia-risk was considered to be poor if patients had adverse cytogenetics or were not in CR1. The majority of the grafts was T-cell depleted (94%). High-resolution typing of HLA-A, -B, -C, and -DRB1 alleles was available for analysis in 270 donor-recipient pairs and had in part been performed retrospectively. Results:We evaluated the impact of high-resolution matching for HLA-A, -B, -C and -DRB1 on progression free survival (PFS) and overall survival (OS). Patients who were fully matched (8/8) with their donors (n=170) hadsignificantly superior PFS (40+/-4% vs 26+/-5%, hazard ratio (HR)=0.68; 95%CI 0.50–0.92, p=0.01) and OS (39+/-4% vs 29+/-5%, HR=0.70; 95%CI 0.51-0.96, p=0.03), compared to patients with mismatched (≤7/8) donors (n=100). Superior OS in the 8/8 group appeared to be due to a lower NRM (24+/-4% vs 39+/-5%, HR=0.54; 95%CI 0.35-0.85, p=0.008), while the relapse mortality rate was identical in both groups (37+/-4% vs 32+/-5%). Patients with EBMT risk scores of 1-2 (n=71), 3 (n=77), 4 (n=76) and 5-7 (n=103) had a predicted 5 year OS of 52%, 41% (HR=1.57; 95%CI 0.98-2.52), 29% (HR=2.07; 95%CI 1.32-3.26) and 19% (HR=2.69; 95%CI 1.76-4.11), respectively (p<0.001). Relapse mortality rate and NRM increased with increasing EBMT risk score. As shown in the table, the impact of allele-matching on OS was most evident in the EBMT low-risk group. EBMT low-risk (1-2) patients with 8/8 donors showed excellent 5 year OS compared to EBMT low-risk patients with ≤7/8 donors (73+/-8% vs 35+/-12%). The favorable impact of a fully matched donor was absent in patients with higher EBMT risk scores. Conclusions:Both the EBMT risk score and the degree of allele-matching independently predicted outcome after URD alloSCT. The predictive value of allele-matching was especially evident in EBMT low-risk patients, while patients with the highest EBMT risk scores (>4) had a dismal outcome, despite allele-matching. These results emphasize the importance of incorporating age, disease stage, donor-recipient gender combination and time interval from diagnosis to transplantation (EBMT risk score parameters) as well as high-resolution HLA-typing in the risk assessment prior to URD alloSCT. As excellent OS was noted in well matched EBMT low-risk patients, our data underscore the importance of an immediate search for an unrelated donor in poor-risk leukemia patients in CR1 below the age of 40, who should then receive their alloSCT as early consolidation therapy following induction chemotherapy.5-year overall survival (OS) rates with 95% CI, and HR with 95% CI by EBMT risk group and matchingEBMT risk score8/8 donors≤ 7/8 donorsN5-year OS [%] (95% CI)N5-year OS [%] (95% CI)HR* (95% CI)0.72)1-23873 (54-85)2035 (14-58)0.30 (0.13-0.72)34545 (28-61)2534 (16-53)0.68 (0.35-1.30)43731 (16-48)2234 (14-54)0.86 (0.44-1.68)5-7509 (2-24)3318 (7-34)1.02 (0.61-1.69)*HR of 8/8 donors (n=170) compared to ≤ 7/8 donors (n=100) Disclosures:No relevant conflicts of interest to declare.

Graft-Vs-Leukemia Effects of Allogeneic Stem Cell Transplantation from HLA-Haploidentical Family Members as Compared to HLA-Identical Sibling Donors

Allogeneic stem cell transplantation produces a strong graft-versus-leukemia effect which may be enhanced by HLA-mismatches and immune recognition as a result of pregnancy. Therefore we compared the results of HLA-haploidentical transplantation (N=113) to those of HLA-identical sibling (N=195) transplantation performed in the same time. Cases were matched by disease category (acute myeloid leukemia-myelodysplastic syndromes, AML/MDS, acute lymphoid leukemia ALL and lymphoma-chronic lymphocytic leukemia NHL/CLL) and stage of the disease (early, intermediate and advanced). HLA-haploidentical transplants were performed with unmodified bone marrow followed by CD6-depleted mobilized blood stem cells on day 6.; patients with leukemia were in more advanced disease in leukemia, they were younger and more often male. In multivariate analysis survival was influenced by HLA-mismatch, stage of the disease and age of the patient, but conditioning treatment and CMV-seropositivity had no significant effect. Transplant related mortality was influenced by the age of the patient and HLA-match, to a lesser extent by the disease category and the stage, whereas CMV-seropositivity and conditioning had no influence. Remission duration was dependent on the stage of the disease, the donor recipient gender combination and the conditioning treatment in univariate analysis; in multivariate analysis only CMV-seropositivity had a poor prognostic impact. In comparable disease stages the relapse rate was not different in HLA-haploidentical from HLA-identical transplantation as was the rate of acute GVHD. In contrast the rate of chronic GVHD was lower in HLA-haploidentical transplantation. In ALL, relapse rate and remission duration was inferior with non-myeloablative conditioning as compared to myeloablative total body irradiation. In HLA-haploidentical transplantation the response rate of leukemia was better in patients homozygous for the cross reactive HLA-C group given a transplant from a heterozygous donor suggestive of NK activity. This GVL activity was not associated with GVH activity. Similarly maternal donors were superior to paternal donors and female donors in male recipients better than other gender combinations for the control of leukemia without increased GVHD. Non-inherited maternal antigen (NIMA) and inherited paternal antigen (IPA) in the graft-vs-host direction had a weak influence on the relapse rate, but no influence on GVHD. On an observational basis several sons and daughters transplanted with stem cells from the mother had a strong GVL effect without any signs of GVHD. However two have been lost due to untreatable pulmonary complications. Donors with cytotoxic antibodies have been excluded from donation, but cellular reactivity will have to be assessed in more detail. Recent progress in controlling EBV-associated disease by selection of donor T cells without expansion will improve HLA-haploidentical transplantation and show the way to selecting donor with the appropriate immune repertoire including reactivity to leukemia.

Influence of Donor-Recipient Gender Mismatch in Early Outcome After Lung Transplantation

Objective Donor and recipient genders are not considered in lung transplantation (LT) programs. However, recent data have suggested a possible biologic effect of gender combination on the outcome of LT. We ought to evaluate the effect of gender combinations on early survival in a single-institution experience in transplant recipients. Methods We analyzed the potential effect of donor-recipient gender combinations (male [M] or female [F]) on early survival of all patients whose LTs were performed between January 1999 and December 2006. Patients were distributed into 4 groups: M donor to M recipient (M-M group); M donor to F recipient (M-F group); F donor to F recipient (F-F group); and F donor to M recipient (F-M group). The comparison between groups was performed using two-tailed Fisher exact test and analysis of variance (ANOVA). Results During the study period, 152 LTs were performed in 149 patients, including 99 male donors and 53 female donors. The mean age of the recipients was 54 ± 10 years (range, 14–70). The 30-day survival rate was 86% (95% confidence interval [CI], 77%– 92%) for the M-M group, 67% (95% CI, 41%–87%) for the F-M group, 89% (95% CI, 52%–100%) for the M-F group, and 83% (95% CI, 66%–93%) for the F-F group. No differences were observed between group survivals according to the Fisher test ( P = .27). Conclusions We found no association between donor-recipient gender mismatch and improved survival in lung transplant recipients. Further investigation is needed to finally understand the possible role of gender combinations in LT.

The Influence of Gender on Survival After Heart Transplantation

Because of a shortage of deceased donors, more than one-third of patients die during the waiting period for transplantation. This study was conducted to analyze the influence of gender on survival after heart transplantation. We retrospectively reviewed the recipients after primary orthotopic heart transplantation. According to gender, patients were divided into four groups: male donor to male recipient, male donor to female recipient, female donor to male recipient, and female donor to female recipient. Kaplan-Meier survival curves were plotted with log-rank tests. Cox regression analysis with dummy variables were used to examine the effects of donor gender, recipient gender, and donor–recipient gender combinations on survival after heart transplantation. The data did not show any significant effect of donor gender, recipient gender, or donor–recipient gender combinations on patient survival, using the methods of log-rank test and Cox regression with dummy variables. Based on our results, we concluded that gender was not an important factor in organ allocation.

Validação do Escore de Risco do EBMT em 1.084 pacientes portadores de leucemia mielóide crônica submetidos ao transplante alogênico de células precursoras hematopoiéticas no Brasil

Abstract This study is a retrospective analysis of 1084 patientstransplanted in ten Brazilian centers in the period fromFebruary 1983 to March 2003. The main objective was tovalidate the EBMT risk score in chronic myeloid leukemiapatients submitted to allogeneic hematopoietic stem celltransplantation.The risk score is based on five variables: recipientage, disease stage, donor type [HLA-identical related,matched unrelated or unmatched donor], donor-recipientgender combination, and interval from diagnosis totransplantation. The total of the points allocated to eachof the different criteria stratifies the patients in risk scoregroups of from zero to seven.The mean age of the evaluated patients in this studywas 33 years old (from 6 to 58 years), with 647 (59.7%)male and 437 (40.3%) female. At the time of transplantation,898 (82.8%) were in the chronic phase, 146 (13.5%) in theaccelerated phase and 40 (3.7%) in the blastic phase. Onehundred and fifty-one (13.9%) of the patients were under20 years old, 620 (57.2%) between 20 and 40 years old and313 (28.9%) were older than 40. The transplantation wasHLA-identical related in 1025 (94.6%) of the recipients andnon-related in only 59 (5.4%) of the cases. The donor-recipient gender combination was female into male in 283(26.1%) of the transplantations, whilst other combinationsoccurred in 801 (73.9%) cases. The interval from diagnosisto transplantation was less than 12 months in 223 (20.6%)patients and greater than 12 months in 861 (79.4%). In 179(16.6%) patients, the risk score was 0 or 1, in 379 (36.6%)the score was 2, in 345 (31.8%) it was 3, in 135 (12.5%) itwas 4 and in the remaining 28 cases (2.6%) the score was5 or 6. There were no cases with a score of 7.The overall survival rate was 49.23% at a median of67 months. The disease free survival rate was 50.36%, thetransplant-related death rate was 45.18% and the incidenceof relapse was 24.66%.Patients with risk scores of 0 and 1 or 2 in relation tothe overall survival rate did not present with significantdifferences (58.5% - 55.4%: Relative Risk 19). The overallsurvival rate was significant in relation to risk score of 3and greater (44.3%: Relative Risk 53). The criterion, diseasestage, was considered significant. The chronic phase gavean overall survival rate of 54.7%; the accelerated phase27.7% (relative risk of 81) and the overall survival rate inthe blastic phase was 14% (relative risk of 211). The donor-recipient gender combination was also significant with anoverall survival rate of 40.5% (relative risk 33) when thetransplant was female into male. Other combinationspresented with a rate of 52.4%. There were no significantdata of overall survival in relation to the other three criteria.The risk score was significant in respect to thedisease free survival, transplant-related death with scoresof 3 and higher, and incidence of relapse with scores of 5or 6 with values of 45.6%, 48.9% and 73.3% respectively.In isolation, the disease phase was significant in the threeparameters and donor-recipient gender combination onlyin relation to disease free survival and transplant-relateddeath. The results indicate that the potential of overallcure of patients submitted to transplantation isapproximately 50%, and that the EBMT score as it wasdesigned is a decision making tool for indication oftransplantation. Additionally, the results identify thedisease stage and the donor-recipient gender combinationas the two most important independent criteria. With theresults of this independent study, we can confirm that theEBMT risk score for chronic myeloid leukemia is valid andshould be used for clinical decision making whenindicating transplantation.

Gender of donor influences outcome after orthotopic liver transplantation in adults.

Because male and female livers not only differ with respect to estrogen and androgen receptor content, but also demonstrate sexual dimorphism of certain functions, we examined the effect of donor gender on graft survival following liver transplantation (OLTx) in adults. Between February 1981 and February 1988, 982 OLTx procedures were performed in 789 adult patients at the University of Pittsburgh. In this study, OLTx was categorized as a failure if the patient died or required retransplantation within 60 days of the surgery. When the donor-recipient gender combinations were male-male, male-female, and female-female, the failure rates were 28%, 28%, and 36%, respectively. In contrast, 60% of female donor livers failed in male recipients. Compared to the pooled donor-recipient gender combinations, the odds of failure for female-male liver grafts were increased 3.7-fold (95% confidence interval: 6.5, 2.1; P < 0.001). These findings may result, at least in part, from alterations in the sex hormone milieu or changes in the graft estrogen or androgen receptor content.