Human Leukocyte Antigen Matching Research Articles

Clinical-Scale Derivation of Natural Killer Cells From Human Pluripotent Stem Cells for Cancer Therapy

Adoptive transfer of antitumor lymphocytes has gained intense interest in the field of cancer therapeutics over the past two decades. Human natural killer (NK) cells are a promising source of lymphocytes for anticancer immunotherapy. NK cells are part of the innate immune system and exhibit potent antitumor activity without need for human leukocyte antigen matching and without prior antigen exposure. Moreover, the derivation of NK cells from pluripotent stem cells could provide an unlimited source of lymphocytes for off-the-shelf therapy. To date, most studies on hematopoietic cell development from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have used incompletely defined conditions and been on a limited scale. Here, we have used a two-stage culture system to efficiently produce NK cells from hESCs and iPSCs in the absence of cell sorting and without need for xenogeneic stromal cells. This novel combination of embryoid body formation using defined conditions and membrane-bound interleukin 21-expressing artificial antigen-presenting cells allows production of mature and functional NK cells from several different hESC and iPSC lines. Although different hESC and iPSC lines had varying efficiencies in hematopoietic development, all cell lines tested could produce functional NK cells. These methods can be used to generate enough cytotoxic NK cells to treat a single patient from fewer than 250,000 input hESCs/iPSCs. Additionally, this strategy provides a genetically amenable platform to study normal NK cell development and education in vitro.

Sounding the alarm on deaths from suicide and accidents after hematopoietic stem cell transplantation

Sounding the alarm on deaths from suicide and accidents after hematopoietic stem cell transplantation

Comparison of Kidney Paired Donation Transplantations with Living Related Donor Kidney Transplantation: Implications for National Kidney Paired Donation Program

Background: Kidney Paired Donation (KPD) is a rapidly growing modality for facilitating living related donor kidney transplantation (LRDKTx) for patients who are incompatible with their healthy, willing, and living donors. Data scarcity on the outcome of KPD versus LRDKTx prompted us to review our experience. Materials and methods: This was a single-center study of 224 patients on regular follow-up, who underwent LRDRTx from January 2010 to June 2012 at our institute. The aim of this study was to compare short-term graft survival, patient survival and rejection rates of KPD (group 1, n = 34) with those of LRDKTx (group 2, n = 190). All the recipients received triple immunosuppression and thymoglobulin induction in KPD group. Kaplan–Meier curves were used for survival analysis. In group 1, mean recipient age was 35.5 ± 13.2 years, 29 were men and mean donor age was 44.4 ± 8.17 years, 10 were men. In group 2, mean recipient age was 29.1 ± 10 years, 155 were men and mean donor age was 47.5 ± 9.69 years, 74 were men. Mean human leukocyte antigen (HLA) matching in group 1 and 2 was 1 versus 3.2 (p < 0.05). Results: One- and two-year patient survival showed no significant difference between the two groups (97.1%, 97.1% vs. 96.2%, 94.8%, respectively, p = 0.81). Death-censored graft survival also showed no significant difference between the two groups (97.1%, 97.1%, vs. 97.6%, 97.6%, p = 0.73). Acute rejection incidence was also similar (8.7% vs. 9.9%, p > 0.62). Conclusions: Our study showed similar graft survival, patient survival and rejection rates of KPD versus LRDKTx over 2 years post-transplantation, encouraging the use of this approach for national KPD program.

Alternative transplant donor sources

To review the data supporting the use of alternative donors for hematopoietic cell transplantation of patients with high-risk or advanced hematological malignancies. Advances in supportive therapy and technology have improved the safety and efficacy of alternative donors for hematopoietic cell transplantation. Molecular techniques have allowed for better human leukocyte antigen matching of unrelated adult donors. Novel strategies such as adoptive regulatory T cells or posttransplantation cyclophosphamide contributed to better outcomes after partially matched related donors. In umbilical cord blood transplantation, the ability to find adequately dosed single-unit grafts, the utilization of double-unit grafts, and novel methodologies such as ex-vivo expansion, intrabone injection, and priming to accelerate engraftment are promising. Available retrospective studies suggest despite the differences in hematopoietic recovery, risk of graft-versus-host disease, and relapse, long-term outcomes are similar between different alternative donor types. In the absence of a suitable matched related donor, most patients will be able to find an alternative donor to proceed to a potentially curative allogeneic transplantation. Emerging new technologies will further improve the safety and efficacy of alternative donor transplantation. Ongoing and future randomized studies will better define the relative efficacy of alternative donor types.

Graft-versus-Host Disease after Double-Unit Cord Blood Transplantation Has Unique Features and an Association with Engrafting Unit-to-Recipient HLA Match

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor–recipient (but not unit–unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

President of The Transplantation Society, 2010–2012

Professor Gerhard Opelz (Fig. 1) was born in September 1944 in Austria. He was schooled in Austria, and after a period of compulsory military service in the Austrian Army, he attended medical school at the University of Vienna from 1963 to 1970.FIGURE 1: Professor Gerhard Opelz, President, The Transplantation Society, 2010–2012.He found both an interest in immunology and his future wife in Stockholm, where he worked as a physician at the Stockholm Blood Center and was awarded a fellowship by The Swedish Institute in 1970. A Fulbright fellowship in the following year saw him travel to California, where he commenced as a postgraduate research immunologist in the Department of Surgery, University of California School of Medicine. Working with Paul Terasaki, he became an associate professor in 1975, and a very productive period of research in human leukocyte antigen (HLA) and transplantation followed. He was recruited back across the Atlantic in 1981 as the Chair of Transplantation Immunology and the Director of the Department of Transplantation Immunology in the Institute of Immunology, University of Heidelberg, where he has remained to this day. He is one of the best known and most highly published people in the fields of both transplantation and histocompatibility, partly through the Collaborative Transplant Study (CTS), which he initiated in 1982, with currently approximately 400 participating centers in 46 countries. The growth of the data held by the CTS has been evident to anyone in the field, as shown in Figure 2. This has been one of our most important global resources, documenting over the years the various significant influences on transplantation outcomes. Not all of the results from the CTS have been welcomed nor indeed understood—at least initially. In the early 1980s, we learned from the CTS about the blood transfusion effect in renal transplantation, and then in the late 1980s, we learned from the same source that it has now dissipated. The importance of HLA matching has been an important theme of the work, especially with the introduction of more accurate DNA typing techniques, sensitive crossmatching techniques, and the definition of donor-specific antibodies to HLA and to major histocompatibility complex I–related chain A. However, the CTS has also contributed substantially in other areas that require large databases to see through the interfering noise (e.g., posttransplantation lymphoma, the importance of blood pressure control, the development of malignancies in the immunosuppressed patient, and trials of immunosuppression, especially through a randomized controlled study of steroid-free therapy).FIGURE 2: Cumulative growth data of the Collaborative Transplant Study, 1981–2012.Professor Opelz has been honored by many organizations, including the Schiff Award, German Society for Transfusion and Immunohematology; the Clas Högman Lecture, Swedish Society for Blood Transfusion; the Jean Dausset Lecture at the International Jean Dausset Symposium; the Terasaki Lecture, British Society for Histocompatibility and Immunogenetics; the Gold Medal of the Catalan Transplantation Society; the Terasaki Award, American Society for Histocompatibility and Immunogenetics; and the Ceppellini Lecture of the European Federation of Immunogenetics. He has served on many editorial boards and as president and on the councils of many professional societies. We are proud to have him serve as the President of The Transplantation Society.

Rapid, scalable and highly automated HLA genotyping using next-generation sequencing: a transition from research to diagnostics

BackgroundHuman leukocyte antigen matching at allelic resolution is proven clinically significant in hematopoietic stem cell transplantation, lowering the risk of graft-versus-host disease and mortality. However, due to the ever growing HLA allele database, tissue typing laboratories face substantial challenges. In light of the complexity and the high degree of allelic diversity, it has become increasingly difficult to define the classical transplantation antigens at high-resolution by using well-tried methods. Thus, next-generation sequencing is entering into diagnostic laboratories at the perfect time and serving as a promising tool to overcome intrinsic HLA typing problems. Therefore, we have developed and validated a scalable automated HLA class I and class II typing approach suitable for diagnostic use.ResultsA validation panel of 173 clinical and proficiency testing samples was analysed, demonstrating 100% concordance to the reference method. From a total of 1,273 loci we were able to generate 1,241 (97.3%) initial successful typings. The mean ambiguity reduction for the analysed loci was 93.5%. Allele assignment including intronic sequences showed an improved resolution (99.2%) of non-expressed HLA alleles.ConclusionWe provide a powerful HLA typing protocol offering a short turnaround time of only two days, a fully integrated workflow and most importantly a high degree of typing reliability. The presented automated assay is flexible and can be scaled by specific primer compilations and the use of different 454 sequencing systems. The workflow was successfully validated according to the policies of the European Federation for Immunogenetics. Next-generation sequencing seems to become one of the new methods in the field of Histocompatibility.

Renal Transplantation in Secondary Amyloidosis Associated with Tuberculosis

Although end-stage renal disease (ESRD) related to AA amyloidosis nephropathy secondary to tuberculosis is most common in our country, there are limited data concerning patient and graft outcome after renal transplantation (RTx). To the best of our knowledge, this is the first report of RTx in ESRD patient with secondary amyloidosis due to tuberculosis from India. A 30-year-old female with past history of pulmonary tuberculosis 3 years back was admitted with complaint of gradually progressive pedal oedema and nausea for 3 months. Renal biopsy was suggestive of secondary renal amyloidosis with vascular involvement and chronic tubulointerstitial involvement. She was transplanted with kidney from her 28-year-old brother with 3/6 human leukocyte antigen match. She had immediate good graft function without any perioperative complications (cardiovascular, infections, rejection and delayed graft function). She was discharged with serum creatinine of 0.8 mg/dL. Her last serum creatinine level was 0.9 mg/dL with cyclosporine level of 100 mg/dL at 9-month followup without any medical or surgical complication. The quality of life also improved after transplantation. With careful selection, ESRD patients with secondary amyloidosis due to tuberculosis are eligible for RTx with favorable outcome and improved quality of life.

Bayesian Modeling of Pretransplant Variables Accurately Predicts Kidney Graft Survival

Introduction: Machine learning can enable the development of predictive models that incorporate multiple variables for a systems approach to organ allocation. We explored the principle of Bayesian Belief Network (BBN) to determine whether a predictive model of graft survival can be derived using pretransplant variables. Our hypothesis was that pretransplant donor and recipient variables, when considered together as a network, add incremental value to the classification of graft survival. Methods: We performed a retrospective analysis of 5,144 randomly selected patients (age ≥18, deceased donor kidney only, first-time recipients) from the United States Renal Data System database between 2000 and 2001. Using this dataset, we developed a machine-learned BBN that functions as a pretransplant organ-matching tool. Results: A network of 48 clinical variables was constructed and externally validated using an additional 2,204 patients of matching demographic characteristics. This model was able to predict graft failure within the first year or within 3 years (sensitivity 40%; specificity 80%; area under the curve, AUC, 0.63). Recipient BMI, gender, race, and donor age were amongst the pretransplant variables with strongest association to outcome. A 10-fold internal cross-validation showed similar results for 1-year (sensitivity 24%; specificity 80%; AUC 0.59) and 3-year (sensitivity 31%; specificity 80%; AUC 0.60) graft failure. Conclusion: We found recipient BMI, gender, race, and donor age to be influential predictors of outcome, while wait time and human leukocyte antigen matching were much less associated with outcome. BBN enabled us to examine variables from a large database to develop a robust predictive model.

Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments

BackgroundPolicies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue.MethodsDiscrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life.ResultsResponses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches.ConclusionsOur econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.

Strategy for the creation of clinical grade hESC line banks that HLA‐match a target population

Here, we describe a pre-derivation embryo haplotyping strategy that we developed in order to maximize the efficiency and minimize the costs of establishing banks of clinical grade hESC lines in which human leukocyte antigen (HLA) haplotypes match a significant proportion of the population. Using whole genome amplification followed by medium resolution HLA typing using PCR amplification with sequence-specific primers (PCR-SSP), we have typed the parents, embryos and hESC lines from three families as well as our eight clinical grade hESC lines and shown that this technical approach is rapid, reliable and accurate. By employing this pre-derivation strategy where, based on HLA match, embryos are selected for a GMP route on day 3–4 of development, we would have drastically reduced our cGMP laboratory running costs.

A New Kidney Allocation Policy in Chile. Computer Based Simulations

Introduction: Kidney allocation involves ethical and technical aspects that have to be addressed in order to reach a balance between fairness, equity and efficiency. Models based on large populations may not be applicable to small countries, so local rules have to be developed and tried before implementation. In Chile kidneys are allocated based on ABO matching, first to medical priorities and then according to a point scheme that considers human leukocyte antigen (HLA) match (60%), time on the waiting list (20%) and panel reactive antibodies (PRA) (20%), additionally paediatric recipients receive extra points. A new policy being developed maintains ABO matching and medical priorities as first step but incorporates several other steps namely prior donors; 0 mismatch recipients; paediatric recipients and finally all other recipients according to a point scheme that incorporates recipient age, HLA match, PRA, and time on waiting list on similar proportions. The aim of this study is to compare the resulting transplants of the new allocation policy to the older. Methods: Computer generated simulations using actual patients (N=1176) on the Chilean waiting list as of September 2011 and 300 donors generated on the previous 3 years, were analyzed. Several simulations were performed randomly distributing the order of the donors in order to eliminate the importance of this factor on the results. Results: The new policy resulted in a significant decrease in the recipient age from 46 years to 41 and an increase in the number of 0 mismatched transplants from 4% to 6%. The mean HLA mismatch increased from 2,51 to 3,19 and HLA DR mismatch from 0,43 to 0,75. Finally waiting time increased from a mean of 40,2 months to 44,3 months. Conclusions: These results support the idea that improvements in the overall quality of transplants being performed can be achieved by changes in allocation policies. With the changes proposed younger patients are being privileged and compatibility is not (exception being made of 0 mismatched donor-recipient pairs). Increase in waiting time observed is probably due to the transplantation of longstanding patients on the wait list that were not candidates previously due to poor matching. Computer generated simulations can help decide which policies are best suited for each country based on their local characteristics.

A New Kidney Allocation Policy in Chile. Computer Based Simulations

Introduction: Kidney allocation involves ethical and technical aspects that have to be addressed in order to reach a balance between fairness, equity and efficiency. Models based on large populations may not be applicable to small countries, so local rules have to be developed and tried before implementation. In Chile kidneys are allocated based on ABO matching, first to medical priorities and then according to a point scheme that considers human leukocyte antigen (HLA) match (60%), time on the waiting list (20%) and panel reactive antibodies (PRA) (20%), additionally paediatric recipients receive extra points. A new policy being developed maintains ABO matching and medical priorities as first step but incorporates several other steps namely prior donors; 0 mismatch recipients; paediatric recipients and finally all other recipients according to a point scheme that incorporates recipient age, HLA match, PRA, and time on waiting list on similar proportions. The aim of this study is to compare the resulting transplants of the new allocation policy to the older. Methods: Computer generated simulations using actual patients (N=1176) on the Chilean waiting list as of September 2011 and 300 donors generated on the previous 3 years, were analyzed. Several simulations were performed randomly distributing the order of the donors in order to eliminate the importance of this factor on the results. Results: The new policy resulted in a significant decrease in the recipient age from 46 years to 41 and an increase in the number of 0 mismatched transplants from 4% to 6%. The mean HLA mismatch increased from 2,51 to 3,19 and HLA DR mismatch from 0,43 to 0,75. Finally waiting time increased from a mean of 40,2 months to 44,3 months. Conclusions: These results support the idea that improvements in the overall quality of transplants being performed can be achieved by changes in allocation policies. With the changes proposed younger patients are being privileged and compatibility is not (exception being made of 0 mismatched donor-recipient pairs). Increase in waiting time observed is probably due to the transplantation of longstanding patients on the wait list that were not candidates previously due to poor matching. Computer generated simulations can help decide which policies are best suited for each country based on their local characteristics.

Preimplantation Genetic Diagnosis With HLA Matching—A Way to Save a Child

Preimplantation genetic diagnosis can be used to establish a pregnancy with an embryo that is human leukocyte antigen (HLA)-matched to a sibling having a hematological or immunological disease and needing a life-saving bone marrow transplantation. The ethical aspects of this procedure have been discussed intensively. The procedure applies where no unrelated HLA-matching donor is available or when transplantation from an HLA-matching sibling is considered a better solution. It is only offered in a limited number of centers in Europe as this is a challenging procedure. Where both HLA matching and diagnosis of a dominant disease are necessary, only a small proportion of the embryos can be used, and the procedure is not always technically feasible. The clinical pregnancy rate per cycle started is much lower than following normal in vitro fertilization (IVF) due to a high cycle cancellation rate, but the success rate is only somewhat lower when measured per transfer.

Human leukocyte antigen-haploidentical stem cell transplantation using T-cell-replete bone marrow grafts

Once considered too dangerous for all but the sickest of patients, partially human leukocyte antigen (HLA)-mismatched, or HLA-haploidentical, related donor bone marrow transplantation (haploBMT) has seen a revival, thanks to the reduced intensity conditioning (RIC) regimens and graft-versus-host disease (GVHD) prophylaxis with high-dose posttransplantation cyclophosphamide (PT/Cy). RIC haploBMT with high-dose PT/Cy is associated with a cumulative incidence of acute grades II-IV GVHD of approximately 30% and incidences of chronic GVHD and nonrelapse mortality (NRM) less than 15%. These results have been confirmed in single and multicenter clinical trials. PT/Cy appears to nullify the detrimental effects of HLA mismatching on the outcome of haploBMT, thereby permitting the selection of haplo donors based upon criteria other than HLA matching. Overall and event-free survivals of RIC haploBMT compare favorably to the outcomes of RIC unrelated adult donor or umbilical cord blood stem cell transplantation. With its improved toxicity profile, haploBMT is a feasible alternative for patients who lack an HLA-matched donor and can now be applied to treat patients with nonmalignant disorders.

Hematopoietic Cell Transplantation with Cord Blood for Cure of HIV Infections

Hematopoietic cell transplantation (HCT) using CCR5-Δ32/Δ32 stem cells from an adult donor has resulted in the only known cure of human immunodeficiency virus (HIV) infection. However, it is not feasible to repeat this procedure except rarely because of the low incidence of the CCR5-Δ32 allele, the availability of only a small number of potential donors for most patients, and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. In contrast, cord blood (CB) transplantations require significantly less stringent HLA matching. Therefore, our hypothesis is that cure of HIV infections by HCT can be accomplished much more readily using umbilical CB stem cells obtained from a modestly sized inventory of cryopreserved CCR5-Δ32/Δ32 CB units. To test this hypothesis, we developed a screening program for CB units and are developing an inventory of CCR5-Δ32/Δ32 cryopreserved units available for HCT. Three hundred such units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA matched unit with a cell dose of ≥2.5 × 107 total nucleated cells (TNCs)/kg and a 27.9% probability for white adults. With a cell dose of ≥1 × 107 TNCs/kg, the corresponding projected probabilities are 85.6% and 82.1%. The projected probabilities are lower for ethnic minorities. Impetus for using CB HCT was provided by a transplantation of an adult with acute myelogenous leukemia who was not HIV infected. The HCT was performed with a CCR5-Δ32/Δ32 CB unit, and posttransplantation in vitro studies indicated that the patient's peripheral blood mononuclear cells were resistant to HIV infection.

Independent of Nephrectomy, Weaning Immunosuppression Leads to Late Sensitization After Kidney Transplant Failure

Patients returning to dialysis therapy after renal transplant failure have a high rate of human leukocyte antigen antibody sensitization, and sensitization has been linked to allograft nephrectomy. We hypothesized that nephrectomy for cause is a consequence of weaning immunosuppression and that weaning leads to sensitization even in the absence of nephrectomy. We examined outcomes in 300 consecutive patients with kidney allograft failure and survival of more than 30 days after failure. We analyzed a subset of 119 patients with a low panel reactive antibody (PRA) before transplantation and follow-up PRA testing at 6 to 24 months after failure (late PRA). By late PRA testing, 56% of patients were highly sensitized (class I or II PRA ≥80%). On multivariate analysis controlling for human leukocyte antigen matching, allograft nephrectomy, and other variables, weaning of immunosuppression predicted high sensitization (odds ratio, 14.34; P=0.004). In a subset of patients, the percentage of those who were highly sensitized increased from 21% at the time of failure on immunosuppressive therapy to 68% by late PRA after weaning (P<0.001). Conversely, patients who maintained immunosuppression showed minimal sensitization after failure. Transplant nephrectomy was required in 41% of patients who weaned immunosuppression versus 0% of the 24 patients who maintained immunosuppression with calcineurin inhibitor therapy after failure (P<0.001). Weaning immunosuppression was a triggering event leading to late rejection and allograft nephrectomy and was an independent predictor of alloantibody sensitization after kidney allograft failure.

Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders

AbstractThe importance of human leukocyte antigen (HLA) matching in unrelated donor transplantation for nonmalignant diseases (NMD) has yet to be defined. We analyzed data from 663 unrelated marrow and peripheral blood stem cell transplants performed from 1995 to 2007 for treatment of NMD. Transplantation from a donor mismatched at the HLA-A, -B, -C, or -DRB1, but not -DQB1 or -DPB1, loci was associated with higher mortality in multivariate analyses (P = .002). The hazard ratio for mortality for single (7/8) and double mismatched (6/8) transplants was 1.29 (0.97-1.72; P = .079) and 1.82 (1.30-2.55; P = .0004), respectively, compared with 8/8 matched transplants. HLA mismatches were not associated with acute or chronic GVHD, but were strongly associated with graft failure. After adjustment for other factors, the odds ratio for graft failure for 7/8 and 6/8 (allele and/or antigen) matched pairs compared with 8/8 matched transplants was 2.81 (1.74-4.54; P < .0001) and 2.22 (1.26-3.97; P = .006), respectively. Patients with NMD should receive transplants from allele matched (8/8) donors if possible. Unlike the case with malignancies, HLA mismatching in NMD is associated with graft failure rather than GVHD.

Role of HLA in Hematopoietic Stem Cell Transplantation

The selection of hematopoietic stem cell transplantation (HSCT) donors includes a rigorous assessment of the availability and human leukocyte antigen (HLA) match status of donors. HLA plays a critical role in HSCT, but its involvement in HSCT is constantly in flux because of changing technologies and variations in clinical transplantation results. The increased availability of HSCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of killer-cell immunoglobulin-like receptor (KIR) genes in HSCT. The influence of nongenetic factors on the tolerability of HLA mismatching has recently become evident, demonstrating a need for the integration of both genetic and nongenetic variables in donor selection.

96-P

Human Leukocyte Antigens (HLA), which is extremely polymorphic, plays an important role in stem cell transplantation. The Chinese Han comprise a large population of approximate 1.3 billion with diverse HLA alleles need to be characterized. Data from 3296 independent, unrelated Chinese Han individuals (1457 recipients and 1839 donors) were provided by China Marrow Donor Program (CMDP) for donor-recipient confirmatory typing. SBT, SSOP/HD-SSOP and SSP methods were used to obtain 4-digit alleles. A total of 49, 86, 50, 63 and 24 HLA-A, B, C, DRB1, and DQB1 alleles were observed. Following ASHI CWD criteria, CWD alleles for Chinese Han in our laboratory test and other laboratory reports do not quite correlate with the ASHI CWD alleles: A ∗ 11:53, A ∗ 02:34, A ∗ 02:53N, B ∗ 27:24, B ∗ 46:02, B ∗ 55:12, C ∗ 01:06, C ∗ 03:17, C ∗ 06:06, C ∗ 07:66, C ∗ 07:67, C ∗ 08:22, DRB1 ∗ 12:10, DQB1 ∗ 03:13 and DQB1 ∗ 06:05 are CWD, but are not included in the ASHI CWD list. A series of alleles are Well-Documented alleles and listed in the ASHI CWD list. Conversely, A ∗ 26:03, B ∗ 51:03, C ∗ 12:05, C ∗ 15:09, C ∗ 15:11, C ∗ 17:03, DRB1 ∗ 11:07, DRB1 ∗ 11:11, DRB1 ∗ 13:05, DRB1 ∗ 13:13, DRB1 ∗ 14:06, DRB1 ∗ 14:12, DRB1 ∗ 14:22, DRB1 ∗ 14:25 and DQB1 ∗ 06:11 are rare alleles, but are included in the ASHI CWD list. HLA Ethnic diversity is the main reason for the differences in HLA alleles worldwide. The ASHI HLA CWD alleles help reduce the workload and expenses in high-resolution donor registries and the HLA allele frequencies provide a basis from which to predict the chances of finding HLA matching donors. Our data will be meaningful for the CMDP, for other worldwide donor registries, and for an updated ASHI CWD alleles list.