Donor-recipient Human Leukocyte Antigen Matching Research Articles

The Impact of Donor-Recipient Human Leukocyte Antigen Matching on Bronchiolitis Obliterans-Free Survival Among Lung Transplant Recipients With Connective Tissue Diseases.

The development of connective tissue disease-associated lung diseases (CTD-LD) occurs in association with specific human leukocyte antigens (HLA). For CTD-LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes. Using the Scientific Registry of Transplant Recipients, we assessed whether CTD-LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)-free survival based on the degree of donor HLA matching. This included overall degree of donor-recipient HLA matching, donor-recipient matching at DR loci, and recipient matching with specific donor HLA antigens associated with the development of pulmonary disease in their condition. Among 1413 patients with CTD-ILD, highly HLA-matched donor-recipients did not have worse adjusted survival (hazard ratio [HR]=0.93, 95% confidence interval [CI]=0.58-1.51, p=0.77). Recipients who were fully matched at HLA DR did not have worse survival (HR=0.82, 95% CI=0.56-1.19, p=0.29). Finally, among individual CTD-LD, including rheumatoid arthritis, systemic sclerosis, the idiopathic inflammatory myopathies, and systemic lupus erythematous, transplant with a donor expressing HLA antigens associated with lung manifestations in these conditions was not associated with worse BOS-free survival. Among transplant recipients with CTD-LD, HLA donor-recipient matching, including at the DR loci, does not result in worse BOS-free survival. Based on these findings, there is no reason to treat these as unacceptable antigens when considering donor offers for CTD-LD candidates.

Analysis of Risk Factors for Hepatic Sinusoidal Obstruction Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients

Background: Hepatic sinusoidal obstruction syndrome (SOS), which is also called veno-occlusive disease of the liver, remains a serious complication after hematopoietic stem cell transplantation (HSCT). Over the last years, some risk factors have already been identified to be associated with SOS. However, the cause of SOS is still not fully understood and the mortality remains high, especially for SOS leading to multi-organ failure with a mortality rate up to 84%. The aim of our study was to analyze several risk factors of SOS in pediatric patients undergoing allogeneic HSCT. In addition, we investigated new potential risk factors. Methods: We retrospectively analyzed 105 children who underwent allogeneic HSCT for the first time and did not receive a defibrotide prophylaxis. All transplantations were performed between January 2007 and December 2018 in a single center. The median age was 8.6 years and stem cell source was either bone marrow (n = 74) or peripheral blood (n = 31). Underlying diseases were acute lymphoblastic leukemia (n = 27), acute myeloid leukemia (n = 25), myelodysplastic syndrome (n = 14), lymphoma (n = 2), solid tumor (n = 12) and genetic disease (n = 25). All patients received a myeloablative conditioning regimen. We analyzed the transplantation-related factors graft source, donor-recipient human leukocyte antigen match, donor age, donor sex and conditioning regimen based on busulfan or total body irradiation. Furthermore, we investigated the patient-related factors patient age, patient sex, prior treatment with gemtuzumab ozogamicin as well as the following laboratory parameters: aspartate transaminase, alanine transaminase, cholinesterase, glutamyl transpeptidase, lactate dehydrogenase, alkaline phosphatase, ferritin, albumin, total bilirubin, C-reactive protein and international normalized ratio (INR). All laboratory parameters were measured before HSCT and cutoffs were determined by reference values and receiver operating characteristic (ROC) curves. SOS was defined by modified pediatric Seattle criteria up to day +30 after HSCT because nearly all transplantations were performed before the new pediatric criteria of the European Society for Blood and Marrow Transplantation have been published. In univariate analysis, chi-square test and Fisher's exact test were used. Additionally, the Mann-Whitney U-test was performed to compare the median values of continuous variables. Significant variables (P < .05) were entered in multivariate analysis, which was carried out by using backward stepwise logistic regression. Results: SOS occurred in 15 out of 105 transplantations (14.3%). The median time of SOS onset was 12 days after HSCT (range, 1 day - 26 days). Three patients died of multi-organ failure following SOS (20%). This mortality rate was very low compared to other studies because our patients were treated with defibrotide immediately after being diagnosed with SOS. In univariate analysis, we found a significant association between patient age <1 year and SOS (Odds Ratio (OR) = 7.25, P = .037). Furthermore, a prior treatment with gemtuzumab ozogamicin (OR = 11.00, P = .020) showed a significant correlation. Patients who developed SOS had a significantly higher median ferritin level (2816.9 ng/mL vs. 1554.0 ng/mL, P = .026). Based on this observation, different ferritin cutoffs were selected by ROC analysis. Ferritin >1500 ng/mL (OR = 4.00, P = .033), ferritin >2000 ng/mL (OR = 4.69, P = .016) as well as ferritin >2400 ng/mL (OR = 5.29, P = .005) revealed significant P values. Besides these results, INR ≥1.3 (OR = 5.91, P = .009) was significantly associated with SOS. In multivariate analysis, the following variables showed P values less than .05: treatment with gemtuzumab ozogamicin (OR = 9.24, P = .048), ferritin >2400 ng/mL (OR = 5.74, P = .023) and INR ≥1.3 (OR = 8.02, P = .007). Conclusions: Our data confirm the risk factors of young patient age (<1 year), prior treatment with gemtuzumab ozogamicin and high serum ferritin (>2400 ng/mL) in the pediatric population. Moreover, we report for the first time that there is a significant association between high INR (≥1.3) before HSCT and the occurrence of SOS. Especially this new finding could improve the risk stratification of SOS and should be evaluated in further trails. Disclosures No relevant conflicts of interest to declare.

Guidelines for Cord Blood Unit Selection.

Optimal cord blood (CB) unit selection is critical to maximize the likelihood of successful engraftment and survival after CB transplantation (CBT). However, unit selection can be complex because multiple characteristics must be considered including unit cell dose, donor-recipient human leukocyte antigen (HLA) match, and unit quality. This review provides evidence-based and experience-based comprehensive guidelines for CB unit selection. Topics addressed include the use of both the TNC and the CD34+ cell dose, as well as the CD34+ cell to TNC content ratio to evaluate unit progenitor cell content and engraftment potential, the acceptable TNC and CD34+ cell dose criteria that define an adequate single-unit graft, and the indication and acceptable cell dose criteria for double-unit grafts. The acceptable criteria for 6-loci (HLA-A, -B antigen, -DRB1 allele) and 8-allele (HLA-A, -B, -C, -DRB1) donor-recipient HLA match, the evaluation of patients with donor-specific HLA antibodies, and the multiple determinants of unit quality are also reviewed in detail. Finally, a practical step-by-step guide to CB searches and the principles that guide ultimate graft selection are outlined.

Hematopoietic Stem Cell Transplantation in Children with Refractory Acute Lymphoblastic Leukemia

▪PurposeIt is difficult to decide whether children with leukemia who could not achieve complete remission (CR) after relapse or primary induction failure should undergo transplantation. Nonetheless, allogeneic hematopoietic stem cell transplantation (HSCT) is a possible approach for refractory acute leukemia including acute lymphoblastic leukemia (ALL). Even after refractory to conventional chemotherapy, a graft versus leukemia (GVL) effect could be expected to some extent. This approach is considered to be experimental because the mortality rate of HSCT is extremely high. A previously conducted large-scale study showed that age younger than 10 years was a factor of good prognosis; however, the details in children are unclear. The purpose of this retrospective analysis was to describe the outcomes and risk factors of HSCT for children with refractory ALL.Patients and MethodsThe data was collected through the Transplant Registry Unified Management Program (TRUMP) system, the registry of The Japan Society for Hematopoietic Cell Transplantation. In total, 325 patients with ALL younger than 21 years old when HSCT was performed between January 2001 and December 2015 and who harbored blasts in peripheral blood and/or bone marrow were analyzed. Both myeloablative regimens and reduced-intensity conditioning regimens were analyzed. Patients were classified as having poor-risk cytogenetics with either t(4;11), t(9;22), t(8;14), hypodiploidy or near triploidy, or more than 5 cytogenetic abnormalities. Other ALL cytogenetic findings were classified as other abnormalities or normal. Myeloablative conditioning was defined as total body irradiation (TBI) of >8 Gy and the administration of 8 mg/kg of busulfan (BU), >140 mg/m2 of melphalan, or >10 mg/kg of thiotepa. All other regimens were analyzed as reduced-intensity conditioning HSCT, including low-dose TBI (≤8 Gy) and low-dose BU (≤8 mg/kg). The graft included bone marrow, peripheral blood stem cells, or cord blood. Overall survival (OS) was used as a primary outcome because for HSCT during relapse, post-HSCT CR was not always achieved or reliably documented.ResultsThe median follow-up time of survivors was 1145 days (range 110-3710). The median age was 11 years. Thirty-five percent of patients had a pre-HSCT performance status (PS) of 0, which corresponds to a Karnofsky PS of ≥90. The rate of pre-HSCT fungal infection was 14%. Fifty-nine patients had more than 25% marrow blasts when HSCT was performed. When HSCT was performed, 10%, 60%, and 30% of patients exhibited primary induction failure, first relapse, and second or later relapse, respectively. Ninety-one percent of patients had neutrophils and 67% exhibited platelet recovery by day 100. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) on day 100 was 43%. The cumulative incidence of chronic GVHD (cGVHD) at 3 years after HSCT was 19%. Two hundred and forty-seven patients died. The causes of death were leukemia progression (57%), followed by graft failure (11%), GVHD (10%), hemorrhage (6%), and infection (5%). The 3-year OS rate in all the patients was 22% (95% confidence interval (CI), 18-27). Age, white blood cell count at diagnosis, prior history of central nervous disease, disease status, conditioning regimens, donor-recipient human leukocyte antigen match, graft type, or year in which HSCT was performed did not affect the OS. Grade ≥2 aGVHD did not affect OS. Whereas Patients with chronic GVHD had better 3-year OS (49%, 95% CI 35-61%) compared to that in patients without chronic GVHD (22%, 95% CI 16-29%) (p = 0.001) (Figure 1). Multivariate analysis showed that other than cGVHD, low PS (relative risk (RR): 2.53), blasts in bone marrow greater than 25% (RR: 1.43), T cell phenotype (RR: 1.86), high-risk or normal cytogenetics (RR: 1.42), and a history of HSCT (RR: 1.90) were significant adverse pre-HSCT variables (Table 1). Patients who had 0 or 1 (n = 113), 2 (n = 113), and 3-5 pre-HSCT variables (n = 99) had 42% (95% CI, 32-51), 17% (95% CI, 10-25), and 6% (95% CI, 2-13) 3-year OS, respectively (Figure 2).ConclusionSome patients with refractory pediatric ALL achieved relatively long survival following HSCT in the relapsed period, especially when a GVL effect was obtained. A scoring system using pre-HSCT variables should help decide whether HSCT should be performed or not. HSCT is worth considering for children who have undergone ≤2 pre-HSCTs. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Should We Revisit HLA Matching to Improve Long-Term Graft Outcomes?

We present here an overview of the needs and requirements for human leukocyte antigen (HLA) matching, explain and explore the potential benefits of epitope matching, and discuss the benefits of allele-level high-resolution matching at all HLA loci, i.e. HLA-A, -B, -DR, -DQ and -DP, for donor selection needs during renal transplantation. Donor recipient HLA matching has a substantial impact on organ transplantation by prolonging graft survival, minimizing rejection episodes, preventing sensitization, providing a better chance for retransplantation and reducing the percentage of deaths due to graft dysfunction. Despite these advantages, the utility of HLA matching has been challenged, mainly because of the availability of highly effective immunosuppressive agents clubbed with steady improvements in short-term graft survival. Moreover, the risk associated with prolonged periods on dialysis while waiting for an optimally matched donor is minimized. There is a need to strike a balance between the benefits of HLA matching and problems associated with finding such a donor. A more viable alternative would be to find a donor with mismatches having a low probability of inducing humoral responses.

Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival

A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p < 0.01). Matching at the C locus was not associated with a decreased risk of graft loss (median graft survival: 13.1 years [95% confidence interval {CI}, 11.5-14.8] in C-no vs 15.1 years [95% CI, 13.5-16.6) in C-match, p = 0.44 log-rank; hazard ratio, 0.93; 95% CI, 0.76-1.15; p = 0.52). DQ-match did not differ from DQ-no in any of the analyzed patient factors, except DQ-match was more likely to have high degree of matching at the A, B, and DR loci vs DQ-no (9.8% vs 3.2%, p < 0.01). Matching at the DQ locus was not associated with decreased risk of graft loss (median graft survival: DQ-no, 13.1 years [95% CI, 11.7-14.6) vs DQ-match, 13.0 years [95% CI, 11.4-14.6], p = 0.80, log-rank; hazard ratio, 0.95; 95% CI, 0.81-1.1; p = 0.51. Complete typing at the C locus of both donor and recipient occurs less often then typing at the DQ locus. A higher degree of donor-recipient HLA matching at the C locus or the DQ locus appears not to confer any graft survival advantage.

Association of human leukocyte antigen donor-recipient matching and pediatric heart transplant graft survival.

The effect of donor-recipient human leukocyte antigen (HLA) matching on outcomes remains relatively unexplored in pediatric patients. The objective of this study was to investigate the effects of donor-recipient HLA matching on graft survival in pediatric heart transplantation. The UNOS (United Network for Organ Sharing) database was queried for heart transplants occurring between October 31, 1987, and December 31, 2012, in a recipient aged ≤17 years with ≥1 postoperative follow-up visit. Retransplants were excluded. Transplants were divided into 3 donor-recipient matching groups: no HLA matches (HLA-no), 1 or 2 HLA matches (HLA-low), and 3 to 6 HLA matches (HLA-high). Primary outcome was graft loss. Four thousand four hundred seventy-one heart transplants met the study inclusion criteria. High degree of donor-recipient HLA matching occurred infrequently: HLA-high (n=269; 6%) versus HLA-low (n=2683; 60%) versus HLA-no (n=1495; 34%). There were no differences between HLA matching groups in the frequency of coronary vasculopathy (P=0.19) or rejection in the first post-transplant year (P=0.76). Improved graft survival was associated with a greater degree of HLA donor-recipient matching: HLA-high median survival, 17.1 (95% confidence interval, 14.0-20.2) years; HLA-low median survival, 14.2 (13.1-15.4) years; and HLA-no median survival, 12.1 (10.9-13.3 years) years; P<0.01, log-rank test. In Cox-regression analysis, HLA matching was independently associated with decreased graft loss: HLA-low versus HLA-no hazard ratio, 0.86 (95% confidence interval, 0.74-0.99), P=0.04; HLA-high versus HLA-no, 0.62 (95% confidence interval, 0.43-0.90), P<0.01. Decreased graft loss in pediatric heart transplantation was associated with a higher degree of donor-recipient HLA matching, although a difference in the frequency of early rejection or development of coronary artery vasculopathy was not seen.

The influence of human leukocyte antigen matching on outcomes in pediatric heart transplantation.

Previous adult heart transplantation studies have demonstrated that donor-recipient human leukocyte antigen (HLA) matching results in reduced graft failure and improved patient survival. No study has examined these effects in children. This study investigated the effect of HLA matching on outcomes in pediatric heart transplantation. All pediatric heart transplantation data for patients 0-18 years of age available from the United Network for Organ Sharing Transplant Registry from 1987 to 2009 were analyzed retrospectively. Donor-recipient HLA matching at loci A, B, and DR (0-6) was compared with graft survival and recipient survival. For this study, 3,751 pediatric cardiac transplantation events with complete HLA matching data were identified and grouped as having 0 to 2 matches (3,416 events) or 3 to 6 matches (335 events). The 3- to 6-match group had less graft failure than the 0- to 2-match group (28.7% vs 34.4%; p = 0.035) and greater patient survival by 5 years (81% vs 72%; p = 0.045) and 10 years (66% vs 55%; p = 0.005) after transplantation. The HLA-DR matching alone resulted in less graft failure (p = 0.038) and improved patient survival (p = 0.017). A higher degree of HLA matching in pediatric heart transplantation is associated with decreased graft failure and improved patient survival. In this study, decreased graft failure rates and superior survival also were seen with DR matching alone.

Effect of race on outcomes after allogeneic hematopoietic cell transplantation for severe aplastic anemia

We compared outcomes after hematopoietic cell transplantation in patients of African American (n = 84) and Caucasian (n = 215) descent with severe aplastic anemia. African Americans and Caucasians were matched for age, donor-recipient human leukocyte antigen match, graft type, and transplantation year. The median follow-up of surviving patients was 5 years. In multivariate analysis, overall mortality risks were higher for African Americans compared to Caucasians (relative risk 1.73, P = 0.01). The 5-year probabilities of overall survival adjusted for interval from diagnosis to transplantation, and performance score was 58% for African Americans and 73% for Caucasians. The day-100 cumulative incidence of grade III-IV, but not grade II-IV acute graft-versus-host disease (GVHD), was higher in African Americans compared to Caucasians (29% vs. 13%, P = 0.006). Although the 5-year cumulative incidence of chronic GVHD was not significantly different between the racial groups, African Americans were more likely to have extensive chronic GVHD compared to Caucasians (72% vs. 49%, P = 0.06). Survival differences between Caucasians and African Americans can be attributed to multiple factors. Our data suggest that some of the observed survival differences between Caucasians and African Americans may be explained by higher rates of acute GVHD and severity of chronic GVHD.

Is living donor liver transplantation really equivalent to deceased donor liver transplantation?

Is living donor liver transplantation really equivalent to deceased donor liver transplantation?

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 Unrelated Cord Blood Transplantation and HLA-Mismatched Unrelated Bone Marrow Transplantation for Adults with Leukemia

Recent advances in unrelated cord blood transplantation (UCBT) and high-resolution typing of human leukocyte antigen (HLA) from an unrelated donor have increased choices in alternative donor/stem cell source selection. We assessed HLA-mismatched locus-specific comparison of the outcomes of 351 single-unit UCB and 1,028 unrelated bone marrow (UBM) adult recipients 16 years old or older at the time of transplantation who received first stem cell transplantation with myeloablative conditioning for acute leukemia or myelodysplastic syndromes. With adjusted analyses, HLA 0 to 2 mismatched UCBT showed similar overall mortality (relative risk [RR] = 0.85, 95% confidence interval [CI], 0.68-1.06; P = .149) compared with that of single-HLA-DRB1-mismatched UBMT. UCBT showed inferior neutrophil recovery (RR = 0.50, 95% CI, 0.42-0.60; P < .001), lower risk of acute graft-versus-host disease (RR = 0.55, 95% CI, 0.42-0.72; P < .001), and lower risk of transplantation-related mortality (RR = 0.68, 95% CI, 0.50-0.92; P = .011) compared with single-HLA-DRB1-mismatched UBMT. No significant difference was observed for risk of relapse (RR = 1.28, 95% CI, 0.93-1.76; P = .125). HLA 0 to 2 antigen-mismatched UCBT is a reasonable second alternative donor/stem cell source with a survival outcome similar to that of single-HLA-DRB1-mismatched or other 7 of 8 UBMT.

Transplant Outcomes in Acute Leukemia (I)

Umbilical cord blood (UCB) has gradually emerged over the last decade as an alternative source of hematopoietic cells for transplantation in children and adults with high-risk or advanced hematologic malignancies who do not have a suitably matched related or unrelated adult donor. This increase in use of UCB is due to favorable results in children, growing availability of UCB units with large cell doses, less stringent donor-recipient HLA matching, and rapid identification and acquisition of the unit. In children with acute leukemia, the data support similar leukemia-free survival after transplantation of human leukocyte antigen (HLA)-matched and one or two HLA-mismatched UCB and HLA-matched unrelated donor bone marrow. In adults with acute leukemia, some reports suggest a survival advantage after transplantation of matched unrelated bone marrow compared to UCB, while others report similar leukemia-free survival. Work is in progress to improve hematopoietic recovery and lower early transplant-related deaths, the two major limitations to a successful outcome after UCB transplant. The importance of HLA-matching and cell dose on outcomes after UCB transplantation support the need for an even greater investment in public cord blood banks. Simultaneously searching of accredited cord blood banks and bone marrow donor registries for patients without an HLA-matched sibling thought to benefit from hematopoietic stem cell transplantation (HSCT) is encouraged.

The Effect of High-Resolution Donor-Recipient HLA Matching and Mismatching Frequencies On Choosing Donor in Chinese Population for Unrelated Allo-HSCT.

Abstract 4503The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor (URDs) transplantation. Hematopoietic stem cell transplantation (HCT) from volunteer URDs may give a chance of cure for patients with malignant hematological diseases. Although donor-recipient HLA matching is associated with better outcomes, many are not able to identify an HLA-A, -B, -C, -DRB1, DQB1 matched URD and are faced with choosing the closest matching among the available donors. The Chinese Marrow Donor Program (CMDP) has completed a retrospective high-resolution HLA typing on sufficient patient-donor pairs to analyze high resolution matching and mismatches probability at specific loci. These data are critical for selecting the best available partially HLA-matched donor for patients undergoing HLA-mismatched URD HCT. We have performed high-resolution typing for HLA-A,-B,-C,-DRB1,-DQB1 by using SBT, SSOP and SSP techniques on 1092 donors and 931 patients from the data base of CMDP. Among 1092 donors, the allele with highest frequency were HLA-A*1101, A*0201, A*2402, A*0207, A*3303, A*0206 and A*3001; HLA-B*4001, B*4601, B*5801, B*1302, B*1501, B*5101and B*1301; HLA-Cw*0102, Cw*0702, Cw*0304, Cw*0801, Cw*0602, Cw*0303, Cw*0302 and Cw*0401; HLA-DRB1*0901, DRB1*1501, DRB1*1202, DRB1*0701, DRB1*0803, DRB1*0405, DRB1*0301 and DRB1*1101; HLA-DQB1*0301, DQB1*0303, DQB1*0601, DQB1*0202, DQB1*0602, DQB1*0302, DQB1*0401, DQB1*0201 and DQB1*0502. The probability of HLA high-resolution DNA matching between 1092 donors and 931 patients(10/10 match) was 16.7%. Mismatching at a single HLA-A, -B, -C, -DRB1 or DQB1 locus (9/10) was 17.7%. A single mismatch at each locus of HLA-A, -Cw,- DRB1,- DQB1,- B was 6.8%, 6.3%, 2.0%, 1.7%, and 0.8%, respectively. Double mismatch (8/10) was 18.4%, such as loci A+ Cw(5.0%), DRB1+DQB1(4.6%) and B+ Cw(3.8%). The donor/patient pairs mismatched between allele of A*0201 and A*0206, A*0201 and A*0207, A*1101 and A*1102, B*4006 and B*4002, B*1501 and B*1527, Cw*0304 and Cw*0302, Cw*0304 and Cw*0303, DRB1*1501 and DRB1*1502, DRB1*1202 and DRB1*1201, DRB1*0406 and DRB1*0403, DRB1*1401 and DRB1*1454, DQB1*0303 and DQB1*0302, respectively, were statistically associated with lower-risk Allo-HSCT. These results suggested that high-resolution DNA matching or mismatching for HLA-A, -B, -C, -DRB1 and DQB1 alleles could be associated with better clinical outcome and higher survival. Furthermore, the identification of high risk mismatch and permissive mismatch would be beneficial for the selection of a suitable donor. Disclosures:No relevant conflicts of interest to declare.

High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation

The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor transplantation. To address this question, National Marrow Donor Program data from 3857 transplantations performed from 1988 to 2003 in the United States were analyzed. Patient-donor pairs were fully typed for HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, and -DPA1 alleles. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 (8/8 match) was the minimum level of matching associated with the highest survival. A single mismatch detected by low- or high-resolution DNA testing at HLA-A, -B, -C or -DRB1 (7/8 match) was associated with higher mortality (relative risk, 1.25; 95% CI, 1.13-1.38; P < .001) and 1-year survival of 43% compared with 52% for 8/8 matched pairs. Single mismatches at HLA-B or HLA-C appear better tolerated than mismatches at HLA-A or HLA-DRB1. Mismatching at 2 or more loci compounded the risk. Mismatching at HLA-DP or -DQ loci and donor factors other than HLA type were not associated with survival. In multivariate modeling, patient age, race, disease stage, and cytomegalovirus status were as predictive of survival as donor HLA matching. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 alleles is associated with higher rates of survival.

Clinical significance of donor–recipient HLA matching on survival after myeloablative hematopoietic cell transplantation from unrelated donors

The application of unrelated donor hematopoietic cell transplantation can be expanded with the use of mismatched donors if human leukocyte antigen (HLA) disparity does not lead to increased morbidity and mortality. The rules that govern permissibility of HLA mismatches are not well defined. The International Histocompatibility Working Group in hematopoietic cell transplantation measured the risks associated with locus-specific disparity in 4796 patients transplanted for low, intermediate, or high-risk hematologic diseases. The permissibility of a given HLA mismatch is in part defined by the locus and by disease risk.

MICA‐STR, HLA‐B haplotypic diversity and linkage disequilibrium in the Hunan Han population of southern China

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. This study was aimed to investigate the haplotypic diversity and linkage disequilibrium between human leukocyte antigen (HLA)-B and (GCT)(n) short tandem repeat in exon 5 of MICA gene (MICA-STR) in a southern Chinese Han population. Fifty-eight randomly selected nuclear families with 183 members including 85 unrelated parental samples were collected in Hunan province, southern China. HLA-B generic typing was performed by polymerase chain reaction-sequence-specific priming (PCR-SSP), and samples showing novel HLA-B-MICA-STR linkage were further typed for HLA-B allelic variation by high-resolution PCR-SSP. MICA-STR allelic variation and MICA gene deletion (MICA*Del) were detected by fluorescent PCR-size sequencing and PCR-SSP. Haplotype was determined through family segregation analysis. Statistical analysis was applied to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities and seven MICA-STR allelic variants were observed in 85 unrelated parental samples, the most predominant of which were HLA-B*46, -B60, -B*13, and -B*15, and MICA*A5, MICA*A5.1 and MICA*A4, respectively. Genotype distributions of HLA-B, MICA-STR loci were consistent with Hardy-Weinberg proportions. The HLA-B-MICA-STR haplotypic phases of all 85 unrelated parental samples were unambiguously assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations, nine of them have not been reported in the literature. Significant positive linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA-B*13 and MICA*A4, HLA-B*38 and MICA*A9, HLA-B*58 and MICA*A9, HLA-B*46 and MICA*A5, HLA-B*51 and MICA*A6, HLA-B*52 and MICA*A6, and HLA-B60 and MICA*A5.1, were observed. HLA-B*48 was linked to MICA*A5, MICA*A5.1 and MICA*Del. HLA-B*5801-MICA*A10 linkage was found in a family. Our data indicated a high degree of haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B in a southern Chinese Han population, the data will inform future studies on anthropology, donor-recipient HLA matching in clinical transplantation and HLA-linked disease association.

Dueling Lymphocytes: Picking the Winner

Dueling Lymphocytes: Picking the Winner

Design and methods of The Collaborative Corneal Transplantation Studies. The Collaborative Corneal Transplantation Studies Research Group.

The Collaborative Corneal Transplantation Studies (CCTS) is a set of two multicenter clinical trials designed to investigate the efficacy of donor-recipient human leukocyte antigen matching and crossmatching. High-risk penetrating keratoplasty patients were enrolled through six clinical centers for either the Antigen Matching Study or the Crossmatch Study. All patients were subject to a common set of examinations, treatments, and evaluation procedures. Standard procedures for the identification of high-risk patients, administration of postoperative medications, and recognition and treatment of immunologic allograft reactions were developed and used successfully. These procedures may serve as guidelines for studies in corneal transplantation. Adoption of these methods by other investigators would facilitate evaluation and comparison of results.