Recruiting blood donors to the Canadian Blood Services Stem Cell Registry: A feasibility assessment.

BACKGROUND: Allogeneic hematopoietic cell transplantation remains limited when stem cell registrants cannot be contacted, are not medically fit, are unavailable, or unwilling to proceed. In a recent report, registrants who were prior blood donors were more likely to be available for donation. In this study, we analyzed extent to which recruiting blood donors to the Canadian Blood Services Stem Cell Registry (CBS SCR) can meet targets for ethnic diversity, age, and proximity to collection facilities. METHODS AND RESULTS: We analyzed 124,496 active blood donors on July 1, 2023 regarding the criteria for recruitment to the CBS SCR. A total of 40,518 (32%) were younger than 36 years of age and 49% were first-time donors (potential new recruits year over year). The ethnicity of blood donors younger than 36 years aligns more closely with the 2021 Canadian census compared to stem cell donors who were also previous blood donors, and to the current total inventory of all registrants on the CBS SCR. Of the blood donors, certain ethnic groups, including Black, Chinese, and First Nations/Indigenous, remain underrepresented. A greater proportion of active whole blood donors live within 400 km of a stem cell collection center (91%) compared to stem cell donors who donated during the past 10 years (80%). CONCLUSIONS: Recruitment of blood donors offers an opportunity to improve the ethnic diversity of the CBS SCR and increase proximity of registrants to stem cell collection centers. The potential improved availability of registrants when matched to patients requires confirmation.

HLA matching between donors and recipients improves clinical liver transplant graft survival.

BACKGROUND AND AIMS: The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. METHODS: This retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs. 4-6 mismatches) and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. RESULTS: Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. CONCLUSION: HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.

Reduced human leukocyte antigen mismatching is associated with more favourable outcomes after unrelated donor haematopoietic stem cell transplantation.

The patient-donor human leukocyte antigen (HLA) match remains the most important prognostic factor for successful unrelated donor haematopoietic stem cell transplantation (UD-HSCT). This single-centre study comprised 125 adult patients with malignant haematological diseases undergoing their first UD-HSCT. The primary goal of this study was to validate the impact of HLA matching on HSCT outcomes, specifically at the HLA-DPB1 and HLA-DRB3/4/5 loci. A multivariable Cox regression analysis with a backward selection algorithm was employed to assess the associations of selected prognostic factors with outcomes after UD-HSCT. Any HLA locus mismatch was found to be associated with an increased incidence of grade II-IV acute graft versus host disease (aGvHD) at 100 days (p = .031; hazard ratio [HR] 1.935) and 6 months (p = .004; HR 2.284) after HSCT. The results of the following analyses also confirmed the strong impact of HLA-DPB1-only mismatch on the incidence of grade II-IV aGvHD at 100-day (p = .006; HR 2.642) as well as at 6-month (p = .007; HR 2.401) time periods. The HLA-DPB1-only mismatch was also shown to be statistically significantly associated with lower relapse incidence (p = .034; HR 0.333). The impact of the HLA-DRB3/4/5 mismatch on outcomes was inconclusive, though the two and more HLA-DPB1 + DRB3/4/5-only mismatches showed a trend towards worse outcomes than a single mismatch. Based on our findings and those of more comprehensive studies, the extended HLA loci typing of patients and donors is suggested to avoid unexpected HLA mismatches during the UD selection.

Modeling unrelated blood stem cell donor recruitment using simulated registrant cohorts: Assessment of human leukocyte antigen matching across ethnicity groups.

BACKGROUND: Human leukocyte antigen (HLA)-matched unrelated donors are not available for some patients considered for allogeneic hematopoietic cell transplantation, particularly among certain ethnic groups. Simulated recruitment modeling can inform efforts to find new matches for more patients. METHODS: Simulated recruits were generated by assigning a pair of donor HLA haplotypes from historical data files and matched against HLA data of patient searches in the Canadian Blood Services Stem Cell Registry. Recruitment cohorts reflected the proportion of five specific ethnic groups in the 2016 Canadian census data. RESULTS: Novel 8/8 HLA matches between simulated recruits and patients increased linearly with larger recruitment cohorts. The proportion of novel 8/8 HLA matches from Caucasian, Hispanic, and Native American/First Nations recruits was equal to or greater than their relative proportion in the recruited cohort (match to: recruit ratio (MRR) ≥ 1). In contrast, African American and Asian & Pacific Islander recruits represented a smaller proportion of novel matches relative to their percentage of the recruited cohort (MRR <1). The proportion of novel 7/8 HLA-matches from each ethnic group was approximately the same as their proportion in the recruited cohort (MRR ~ 1) and high rates of 7/8 HLA-matching already exist within the Canadian Blood Services registry for all ethnic groups. CONCLUSION: Continued large recruitment cohorts are needed to add new 8/8 HLA matches to registry inventories. Likelihoods of novel HLA matches varied across ethnic groups, reflecting varied HLA haplotype frequencies across groups. Simulated cohort modeling can inform recruitment strategies that will generate new donor options for patients.

[Clinical significance of human leukocyte antigen incompatibility in allogeneic hematopoietic stem cell transplantation].

The use of human leukocyte antigen (HLA)-incompatible transplantations, in addition to cord blood transplantation, is rapidly increasing due to the development and refinement of graft-versus-host disease prophylactic treatment with post-transplant cyclophosphamide or anti-thymocyte globulin. However, caution must be observed in interpretating the significance of HLA incompatibility because each transplant source differs, which affect the association between HLA compatibility and transplant outcome. In addition, the loci that should be evaluated, the level of matching (antigen/allele), the direction of incompatibility (graft-versus-host or host-versus-graft), and the combination of incompatible HLA alleles must be understood. Notably, the significance of HLA incompatibility changes with the development and improvement of GVHD prophylactic treatment. Factors that should be prioritized in donor selection should be evaluated in the future. This article outlines the significance of HLA incompatibility in each transplant source.

Patient age and donor HLA matching can stratify allogeneic hematopoietic cell transplantation patients into prognostic groups.

BACKGROUND: Mixed results surround the accuracy of commonly used prognostic risk scores to predict overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. We hypothesize that a simple prognostic score performs better than conventional scoring systems. PATIENTS AND METHODS: OS risk factors, HCT-CI, age-HCT-CI, and augmented-HCT-CI were studied in 299 patients who underwent allo-HCT for myeloid and lymphoid malignancies. A scoring system was developed based on results and validated in a different cohort of 455 patients. RESULTS: Two-year OS was 51% (95% confidence interval (CI) 0.45-0.56); 2-year NRM was 34% (95% CI 0.29-0.39). HCT-CI and associated scores were grouped into 0-2 and ≥3. Age and HLA mismatch status were the only risk factors to affect OS in multivariate analysis (p = 0.02 and 0.05, respectively). HCT-CI and associated scores were not informative for OS prediction. The weighted scoring system assigned 0 to 2 points for age < 50, 50-64, or ≥65, respectively, and 0-1 points for no HLA mismatch versus any mismatch (except HLA-DQ). Distinct 2-year OS (62%, 53%, and 38% [p = <0.001]) and NRM (24%, 34%, and 43% [p = 0.02]) groups were characterized. The scoring system was validated in a second independent cohort with similar results on OS and NRM (p < 0.001). CONCLUSIONS: A simple scoring system based on recipient's age and mismatch status accurately predict OS and NRM in two distinct cohorts of allo-HCT patients. Its simplicity makes it a helpful tool to aid clinicians and patients in clinical decision-making.

Predicting kidney transplant outcomes with partial knowledge of HLA mismatch.

We consider prediction of graft survival when a kidney from a deceased donor is transplanted into a recipient, with a focus on the variation of survival with degree of human leukocyte antigen (HLA) mismatch. Previous studies have used data from the Scientific Registry of Transplant Recipients (SRTR) to predict survival conditional on partial characterization of HLA mismatch. Whereas earlier studies assumed proportional hazards models, we used nonparametric regression methods. These do not make the unrealistic assumption that relative risks are invariant as a function of time since transplant, and hence should be more accurate. To refine the predictions possible with partial knowledge of HLA mismatch, it has been suggested that HaploStats statistics on the frequencies of haplotypes within specified ethnic/national populations be used to impute complete HLA types. We counsel against this, showing that it cannot improve predictions on average and sometimes yields suboptimal transplant decisions. We show that the HaploStats frequency statistics are nevertheless useful when combined appropriately with the SRTR data. Analysis of the ecological inference problem shows that informative bounds on graft survival probabilities conditional on refined HLA typing are achievable by combining SRTR and HaploStats data with immunological knowledge of the relative effects of mismatch at different HLA loci.

Significance of HLA-DQ in kidney transplantation: time to reevaluate human leukocyte antigen-matching priorities to improve transplant outcomes? An expert review and recommendations.

The weight of human leukocyte antigen (HLA) matching in kidney allocation algorithms, especially in the United States, has been devalued in a stepwise manner, supported by the introduction of modern immunosuppression. The intent was further to reduce the observed ethnic/racial disparity, as data emerged associating HLA matching with decreased access to transplantation for African American patients. In recent years, it has been increasingly recognized that a leading cause of graft loss is chronic antibody-mediated rejection, attributed to the development of de novo antibodies against mismatched donor HLA expressed on the graft. These antibodies are most frequently against donor HLA-DQ molecules. Beyond their impact on graft survival, generation of de novo donor-specific HLA antibodies also leads to increased sensitization, as measured by panel-reactive antibody metrics. Consequently, access to transplantation for patients returning to the waitlist in need of a second transplant is compromised. Herein, we address the implications of reduced HLA matching policies in kidney allocation. We highlight the observed diminished outcome data, the significant financial burden, the long-term health consequences, and, more important, the unintended consequences. We further provide recommendations to examine the impact of donor-recipient HLA class II and specifically HLA-DQα1ß1 mismatching, focusing on collection of appropriate data, application of creative simulation approaches, and reconsideration of best practices to reduce inequalities while optimizing patient outcomes.

Recipients Receiving Better HLA-Matched Hematopoietic Cell Transplantation Grafts, Uncovered by a Novel HLA Typing Method, Have Superior Survival: A Retrospective Study.

HLA matching at an allelic-level resolution for volunteer unrelated donor (VUD) hematopoietic cell transplantation (HCT) results in improved survival and fewer post-transplant complications. Limitations in typing technologies used for the hyperpolymorphic HLA genes have meant that variations outside of the antigen recognition domain (ARD) have not been previously characterized in HCT. Our aim was to explore the extent of diversity outside of the ARD and determine the impact of this diversity on transplant outcome. Eight hundred ninety-one VUD-HCT donors and their recipients transplanted for a hematologic malignancy in the United Kingdom were retrospectively HLA typed at an ultra-high resolution (UHR) for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next-generation sequencing technology. Matching was determined at full gene level for HLA class I and at a coding DNA sequence level for HLA class II genes. The HLA matching status changed in 29.1% of pairs after UHR HLA typing. The 12/12 UHR HLA matched patients had significantly improved 5-year overall survival when compared with those believed to be 12/12 HLA matches based on their original HLA typing but were found to be mismatched after UHR HLA typing (54.8% versus 30.1%, P = .022). Survival was also significantly better in 12/12 UHR HLA-matched patients when compared with those with any degree of mismatch at this level of resolution (55.1% versus 40.1%, P = .005). This study shows that better HLA matching, found when typing is done at UHR that includes exons outside of the ARD, introns, and untranslated regions, can significantly improve outcomes for recipients of a VUD-HCT for a hematologic malignancy and should be prospectively performed at donor selection.

A study of selected hematopoietic stem cell donors provided by an intermediate size registry.

OBJECTIVE: Planning new hematopoietic stem cell (HSC) donor recruitment strategies requires a sound understanding of the factors underlying donor selection, especially considering HLA-matching criteria. METHOD: A total of 182 consecutive workups of Swiss donors performed from 2014 to 2017 were analyzed for HLA match level, locus disparities, number of potentially 10/10 matched donors in the international database, donor ranking on the lists, donor date of registration, age, ABO, CMV, gender matching, patient genotype frequency, and country performing the search. RESULTS: Matching status of the selected donors was 10/10 for 38.5%, 10-12/12 for 35.1%, and 8-9/10 for 26.4% donors, without differences in average donor age in the three categories. HLA-A and -C mismatches were most frequent and -DRB1 very rare. 8.2% patients were matched for HLA-DPB1 (12/12). ABO matching was 46.3%, and CMV matching was 59.1%. Based on "HaploStat"-derived genotype frequencies, 50.3% patients belonged to the "good," 38.5% to the "fair," and 11.2% to the "poor" search prognosis categories. 37.9% of transplants were gender-mismatched, and 42.3% of donors were female. CONCLUSION: HLA typing quality (high resolution, all loci typed), great diversity of haplotypes and donor age are main factors impacting the selection of Swiss donors, while gender and ABO matching seem to be of secondary importance.

The long and winding road towards epitope matching in clinical transplantation.

Recent data suggest that HLA epitope matching is beneficial for the prevention of de novo donor specific antibody (DSA) formation after transplantation. In this review, different approaches to predict the immunogenicity of an HLA mismatch will be discussed. The parameters used in these models are often called epitopes but the actual antibody epitope is far more complex. Exact knowledge of the antibody epitope is crucial if epitope matching is also used as a tool to select compatible donors for (highly) sensitized patients. Evidence is provided that it is not always possible to give an exact definition of an antibody epitope. We conclude that HLA "epitope" matching is superior over HLA antigen matching with respect to the prevention of de novo DSA formation and will enhance the prediction of acceptable HLA mismatches for sensitized patients. However, epitope matching at our current level of knowledge will not solve all histocompatibility problems as unexpected antibody reactivity still may occur.

Karyomapping in preimplantation genetic testing for ß-thalassemia combined with HLA matching: a systematic summary.

PURPOSE: To investigate the validity, accuracy, and clinical outcomes of Karyomapping in preimplantation genetic testing (PGT) for ß-thalassemia combined with human leukocyte antigen (HLA) matching. METHODS: A total of 128 cycles from January 2014 to December 2017 were identified, and 1205 embryos were biopsied. The case group included 88 cycles using Karyomapping for PGT-HLA, compared with 40 cycles using polymerase chain reaction-short tandem repeat (PCR-STR) as the control group. RESULTS: There were significant differences in the HLA matching rate (21.34 vs. 14.37%), the matched transferable embryo rate (9.79 vs. 14.07%), the clinical pregnancy rate (65.08 vs. 41.86%), and the spontaneous miscarriage rate (2.44 vs. 22.22%) between the case and control groups. In the case group, nearly 1/3 (33.37%) of the embryos showed aneuploidy. According to the results of single nucleotide polymorphism (SNP) haplotype analysis, the recombination rates of HBB (hemoglobin subunit beta) and HLA were 11.46% and 5.61% respectively. HLA gene recombination was mostly distributed between HLA-A and HLA-B and the downstream region of HLA-DQB1. In addition, STR analysis could be considered in the case of copy-neutral loss of heterozygosity (LOH) in the region where the HLA gene is located. CONCLUSION: Karyomapping contributes to accurate selection of matched embryos, along with aneuploidy screening. However, STRs assist identification in cases of LOH in the target region.

HLA Matching in Pediatric Stem Cell Transplantation.

For several malignant and nonmalignant disorders such as leukemias, lymphomas, or inborn errors of hematopoiesis, stem cell transplantation is the only curative option. Depending on the underlying cause of the disease, the conditioning regimens, source of the stem cells, and graft composition may vary. Possible stem cell donors are selected from databases considering existing major histocompatibility genes of the donor and the recipient. This is currently performed by matching human leukocyte antigen (HLA)-A, -B, and -C for class I, as well as HLA-DRB1 and -DQB1 for class II. Stem cell transplantation for nonmalignant disorders is a specialty of pediatrics. While algorithms for donor selection in these cases are generally similar, the objective of optimizing a possible graft-versus-leukemia effect is less important. In this article, we aim to provide an overview on the current methods for HLA typing and the algorithms for HLA matching. We also address ethical aspects regarding children and minors as stem cell donors.

HLA Matching in Unrelated Stem Cell Transplantation up to Date.

Unrelated hematopoietic stem cell transplantation (HSCT) has evolved from an experimental protocol to a potentially curative first-line treatment in certain disease instances. Factors enabling this transformation were the optimization of treatment protocols and supportive care as well as the availability of a large number of donors worldwide along with the higher quality and reliability of HLA typing. The main criterion for donor selection is HLA compatibility. In this review we discuss the current clinical evidence of HLA matching in unrelated HSCT. In this context, we address methodical aspects of transplantation immunobiology research and discuss the impact of locus and resolution of HLA differences. Furthermore, we address special constellations such as unidirectional mismatches or the presence of nonexpressed alleles as well as HLA alloimmunization and describe the perspective for HLA typing and matching strategies in the future, given the implementation of novel complete or near-complete gene typing approaches using next-generation sequencing short read technology, which are now entering the standard of clinical care.

The Importance of HLA Assessment in "Off-the-Shelf" Allogeneic Mesenchymal Stem Cells Based-Therapies.

The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide "off-the-shelf" cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient's immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an "off-the-shelf" medical product.

Analysis of OPTN/UNOS registry suggests the number of HLA matches and not mismatches is a stronger independent predictor of kidney transplant survival.

HLA matching and mismatching, while inversely related, are not exact opposites. Here we determined the independent effects of HLA matching and mismatching on outcomes in deceased donor kidney transplant recipients. The United Network for Organ Sharing database (1995-2012) was utilized and analyzed for delayed graft function, one-year acute rejection, and death-censored graft survival using combined multivariable models including HLA matching and mismatching. Sensitivity analyses were performed using the subgroup of deceased donor kidney transplant patients after 2003 with more uniform HLA nomenclature and resampling analyses using bootstrapping on complete data available from 96,236 recipients. Individually, both HLA matching and mismatching showed significant associations with graft survival. Adjusting the model to take into account both matching and mismatching simultaneously, the degree of HLA mismatching lost significance while matching continued to have a significant prediction for delayed graft function, the one-year acute rejection rate, and graft survival. Sensitivity analyses and bootstrapping showed similar results for all studied outcomes. Thus, analysis of this large cohort demonstrates the apparent greater association of HLA matching over HLA mismatching on both early allograft events as well as graft survival. Future analyses should preferentially utilize HLA matching as a covariate over mismatching for accurately reflecting impact on graft outcomes.

Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 106 CD 34+ cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor.

The Case for High Resolution Extended 6-Loci HLA Typing for Identifying Related Donors in the Indian Subcontinent.

Three-loci low-resolution (LR) or intermediate-resolution HLA typing is generally considered adequate in the related blood and marrow transplantation (BMT) context. However, a single high-resolution (HR) mismatch may have a similar adverse impact on BMT outcome as an LR one. We sought to determine the frequency of mismatches that may go undetected when standard typing (LR or 3-loci HR) is used compared with 6-loci HR typing for related donor compatibility testing, and to assess its impact on relevant BMT outcomes. We analyzed data from a total of 2554 6-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) HR sequence-based typing (full typing [FT]) from 754 patients, 1011 siblings, and 789 parents done at DKMS Germany (www.DKMS.de) between January 1, 2014, and June 21, 2016. We also studied 38 cases in which the family had undergone 3-loci HLA typing (standard typing [ST]). Patients were from India (70%), Pakistan (22%), and Sri Lanka (8%). The IMGT/HLA database (www.ebi.ac.uk/ipd/imgt/hla) was used to tease out nonpermissive DPB1 mismatches. HLA disparity-related outcomes, such as rejection and graft-versus-host disease (GVHD) were assessed in a retrospective matched-pair cohort of 50 patients (25 with ST and 25 with FT) who underwent BMT for severe thalassemia from compatible related donors. We found fully matched (either 12/12 HR matches or with a single permissive DPB1 mismatch) related donors for 285 patients (38%). Of these donors, 89% were siblings and 11% were parents. The likelihood of matching on an individual locus on LR but not on HR was found to be 5%. A total of 9 donors (3%; 7 siblings and 2 parents) who would have been considered a full match by HR typing on A, B, and DRB1 alone were not a match by extended 6-loci HR typing. Five of these 9 donors had a mismatch on C or DQB1, and 4 had a nonpermissive DPB1 mismatch. In this group, 5 donors (56%) belonged to a consanguineous family, in 2 donors (22%) there was no reported consanguinity, and in 2 donors (22%) consanguinity was unknown. We identified 18 donors (6%; 13 siblings and 5 parents) who would have been considered a 12/12 match by LR HLA typing alone but were found not to match on extended HR typing. In this group, 11 donors (61%) were from consanguineous families, 3 donors (17%) had no reported consanguinity, and in 4 donors (22%) consanguinity was unknown. Outcome analysis showed that the actuarial proportion of patients with GVHD was 4% in the FT group compared with 16% in the ST group, with log-rank P = .1952. The ST group included 2 patients with grade III-IV acute GVHD and 1 patient each with moderate and severe chronic GVHD, whereas the FT group only 1 patient with grade III acute GVHD. We conclude that even in the context of related donors, the use of LR and/or 3-loci (A, B, and DRB1) HR HLA typing might result in a sizable risk of missing a clinically relevant mismatch, which may have an adverse impact on transplantation outcomes. In the Indian subcontinent, this observation is not limited to putatively compatible parents or consanguineous families; we recommend full 6-loci HR HLA typing even for matched related BMTs.

HapLogic: A Predictive Human Leukocyte Antigen-Matching Algorithm to Enhance Rapid Identification of the Optimal Unrelated Hematopoietic Stem Cell Sources for Transplantation.

The search for a suitable human leukocyte antigen (HLA)-matched unrelated adult stem cell donor (URD) or umbilical cord blood unit (UCB) is a complex process. The National Marrow Donor Program (NMDP) developed a search algorithm known as HapLogic, which is currently provided within the NMDP Traxis application. The HapLogic algorithm has been in use since 2006 and has advanced URD/UCB HLA-matching technology. The algorithm has been shown to have high predictive accuracy, which can streamline URD/UCB selection and drive efficiencies in the search process to the benefit of the stem cell transplantation community. Here, we describe the fundamental components of the NMDP matching algorithm, output, validation, and future directions.

High-Resolution Match Rate of 7/8 and 9/10 or Better for the Be The Match Unrelated Donor Registry.

Estimation of the National Marrow Donor Program's Be The Match Registry 8/8 (HLA-A, -B, -C, and -DRB1) high-resolution (HR) unrelated donor (URD) match rate was determined in a prior study for each of the 4 most frequent patient race/ethnic groups in the United States: white (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American (AFA). For patients without an 8/8 HLA-matched URD, a 7/8 match, with a single allele or antigen mismatch, is often accepted by many transplant centers. A follow-up study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Of previously HR tested URDs in the Be The Match Registry, 1344 were randomly selected and treated as pseudo-patients where HR testing was performed to identify a 7/8-matched URD; 98% of WH and over 80% of non-WH race/ethnic groups (HIS, API, and AFA) had at least a 7/8 match identified. In most cases after first testing to identify an 8/8-matched URD, a 7/8-matched URD was identified after typing just 1 URD. Extending criteria to identify a 9/10 match (included HLA-DQB1) showed the 9/10 absolute match rate decreased between 14% and 21% from the 7/8 match rate for the non-WH groups. This study provides a baseline 7/8 and 9/10 or better HLA match rate that can be further supplemented using the additional worldwide URD inventory. URD match rate information can equip centers in clinical planning and the education of patients seeking a life-saving therapy.