scholarly journals The role of HLA-typing in transplantation of hematopoietic stem cells

2017 ◽  
Vol 5 (2) ◽  
pp. 159-153
Author(s):  
V. Khomenko
Keyword(s):  
High Resolution ◽  
Molecular Genetic ◽  
Human Leukocyte ◽  
Cost Effective ◽  
Hla Typing ◽  
Potential Donor ◽  
Hematopoietic Stem ◽  
Literary Sources ◽  
Resolution Level ◽  
Typing Methods

The system of human leukocyte antigen (HLA) and HLA-typing were used to match a potential donor with a recipient for allogeneic hematopoietic stem cell transplantation (HSCT). The HLA matching between donor and recipient is key role in allogeneic HSCT. The mismatch of HLA can cause graft rejection, graft-versus-host disease and decrease survival in patients receiving grafts from both related and unrelated donors. The adverse HLA effect on the outcome depends on the total number of mismatched alleles/loci and the resolution level of the mismatch (antigen or allele level).Thus, the final choice of compatible donor-recipient pairs should be based on high resolution molecular-genetic methods of HLA-typing. Serologic and molecular genetic methods of low resolution HLA-typing, which are cheaper than HLA-typing high-resolution, should be used for donor screening studies. HSCT from a fully compatible donor, matched high-resolution HLA-typing methods gives better results than from partially compatible. In some clinical circumstances, a partially compatible donor may be as effective as fully compatible. The selection of such a donor, taking into account the controversy of data from various literary sources, should be based on own research and experience. Creation and development of a Ukrainian database of donors with the HLA-haplotype specific to the indigenous population will make search of matching pairs of donor recipients more effective and cost-effective.

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

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4503-4503
Author(s):  
Jun He ◽  
Zi-Xing Chen ◽  
Xiaojing Bao ◽  
Qiaocheng Qiu ◽  
Xiaoni Yuan ◽  
...  
Keyword(s):  
High Resolution ◽  
Conflicts Of Interest ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Hla Matching ◽  
Hematopoietic Stem ◽  
Leukocyte Antigen ◽  
Resolution Level ◽  
Selection Of

Abstract Abstract 4503 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 (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.

Superior Outcomes with Matched Unrelated Donors Compared with One Human Leukocyte Antigen Mismatched Related Donors In Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 907-907
Author(s):  
Stefan O. Ciurea ◽  
Rima M. Saliba ◽  
Gabriela Rondon ◽  
Poliana A. Patah ◽  
Fleur Aung ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Resolution ◽  
Graft Failure ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Class I ◽  
Hematopoietic Stem ◽  
Leukocyte Antigen ◽  
Unrelated Donors ◽  
Related Donor

Abstract Abstract 907 Most candidates for hematopoietic stem cell transplantation lack a human leukocyte antigen (HLA)-identical sibling donor; however, many patients may have a related donor with whom they are mismatched at one antigen/allele. It is not known whether such a match is preferable to a matched unrelated donor (MUD). We hypothesized that, in transplantation using related donors, adding a single HLA antigen/allele mismatch, identified through high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1, would be associated with worse outcomes than transplantation using matched unrelated donors. Patients and Methods: To test this hypothesis, we analyzed outcomes (survival, relapse, non-relapse mortality) of 367 patients who received transplants from either a 10/10 MUD (n=318) or a one-antigen/allele mismatched related donor (MRD) by 7/8 HLA typing (n=49) treated during the same period of time (1995-2009) at our institution. All patients had intermediate/high-resolution HLA typing at all 5 loci either prospectively or retrospectively, if treated after or before year 2002. Of the 49 patients treated with mismatched related donors, 28 patients (57%) had one antigen/allele mismatched at HLA class I or II loci (or 9/10), 18 patients (37%) had 2 alleles mismatched (or 8/10), and 3 patients (6%) had 3 alleles mismatched (or 7/10). From the 28 patients with a one-allele mismatch, 24 had class I mismatches at either HLA-A or -B loci, and 4 had class II mismatches at either HLA-DR or -DQ loci. Characteristics between the MUD group and 9/10 MRD group were similar [median age 53 vs. 47 years (p=0.08); AML/MDS diagnosis 84% vs. 82% (p=0.5); active disease at transplant 59% vs. 57% (p=0.9); myeloablatie conditioning 63% vs. 75% (p=0.2); bone marrow stem cells 58% vs. 70% (p=0.2); pentostatin use 14% vs. 11% (p=0.4); median year of transplant 2006 vs. 2004, respectively] except more patients in the MUD group received ATG (96% vs. 68%, p=0.02). Results: Outcomes at 3-years were analyzed for the 28 consecutive patients who had received a transplant from a 9/10 MRD based on 5-loci (including -DQB1) HLA typing. Graft failure was more common in patients treated from 9/10 related donors than from MUD. The incidences of primary and secondary graft failure for the 9/10 MRD were 7% and 14%, respectively, whereas none of the MUD transplant recipients had either primary or secondary graft failure (p= 0.02). Cumulative incidence of progression was 40% vs. 25% (p=0.02, HR 1.9, CI 1.1–3.9), non-relapse mortality 40% vs. 26% (p=0.05, HR 1.9, CI 1.0–3.6) and grade II-IV a GVHD was 27% vs. 38% (p=0.4, HR 0.7, CI 0.3–2.5) for the two groups, respectively. Median survival was 6 months for the 9/10 MRD vs. 18 months for the MUD group. The overall survival and progression-free survival rates were 19% and 45% (p=0.007, HR 1.8, CI 1.2–2.9) and 19% vs. 42% (p=0.006, HR1.8, CI 1.2–2.9), respectively. Outcomes for 9/10 MRD transplant patients with class I mismatches (n=24) were significantly worse than outcomes in those with MUD transplants (n=318). The 2-year actuarial OS rate was 27% for the 9/10 MRD and 48% for the MUD transplant group (HR 1.9; 95% CI 1.1 – 3.1; p=0.01). Conclusion: These results indicate that transplant outcomes for patients treated from a one-antigen/allele mismatch related donor are significantly worse than from a MUD, primarily due to increased non-relapse mortality. Patients receiving transplants form a 9/10 related donors, at least with a class I mismatch, should be treated on investigational protocols. Disclosures: No relevant conflicts of interest to declare.

HLA class II genotyping: two assay systems compared

1995 ◽  
Vol 41 (4) ◽  
pp. 553-556 ◽  
Author(s):  
J Thonnard ◽  
F Deldime ◽  
M Heusterspreute ◽  
B Delepaut ◽  
F Hanon ◽  
...  
Keyword(s):  
Large Scale ◽  
Clinical Laboratory ◽  
Blot Hybridization ◽  
Human Leukocyte ◽  
Hla Typing ◽  
High Rate ◽  
Polymorphism Analysis ◽  
Dot Blot ◽  
Pcr Products ◽  
Typing Methods

Abstract In the last few years, a variety of DNA-based human leukocyte antigen (HLA) typing methods have emerged, revealing the extreme polymorphism of HLA genes. This polymorphism makes it difficult for a clinical laboratory to establish the best HLA typing strategy. In this study we have compared two techniques for performing HLA-DRB typing: a commercial rapid assay based on the polymerase chain reaction (PCR) followed by reverse dot-blot hybridization of the PCR products (the Inno-LiPA assay), and a method based on PCR followed by restriction fragment length polymorphism analysis. We found that both methods provide reliable results with a high rate of concordance (97%) and that Inno-LiPA is convenient for large-scale routine typing. However, if a high-resolution allelic typing is required, each method lacks accuracy but using them in association improves the accuracy of the results.

Results of Alternative Donor Search in Adult Patients with Severe Sickle Cell Disease (SCD) Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2260-2260 ◽  
Author(s):  
Matthew M. Hsieh ◽  
Jennifer Wilder ◽  
Courtney Fitzhugh ◽  
Beth Link ◽  
John F. Tisdale
Keyword(s):  
Cord Blood ◽  
Great Majority ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Potential Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Sibling Donor ◽  
Alternative Donor ◽  
Matched Sibling

Abstract Supportive care has improved the outlook for patients with SCD, but life expectancy remains considerably shorter than those without SCD. The major causes of mortality are end-organ failure, stroke, pulmonary disease, and acute vaso-occlusive crises (VOC). Myeloablative allogeneic HSCT in children under age 16 is curative in the majority. However organ damage that meets severity criteria for HSCT may not become evident until adulthood, at which time conventional myeloablative transplant is no longer an option. Additionally, the great majority of SCD patients do not have a 6/6 HLA-matched sibling donor available. Reduced-intensity conditioning may extend this potentially curative treatment to adults with SCD. Since non-myeloablative transplants may result in mixed donor chimerism, major ABO-mismatch may lead to red cell aplasia, and therefore should be avoided. Finally, cell dose is likely an important parameter in non-myeloablative transplant regimens, potentially further limiting donor availability. We initiated an IRB approved non-myeloablative allogeneic HSCT program for adults with severe SCD for whom a matched sibling donor is available. For those without related donors, we devised a search strategy for alternative donors to establish the feasibility of matched unrelated donor (MUD) or umbilical cord blood (UCB) HSCT. HLA typing was performed for potential donors and patients who on initial screen met at least one the following criteria: stroke, pulmonary hypertension, sickle related nephropathy, or frequent VOC/ACS not improved by HU. Typing at the serologic level was performed for HLA-A,-B, and at the allele level for HLA-DR B1. For patients without matched sibling donors, searches in the National Marrow Donor Program for marrow and cord blood donors were initiated. Since 2003, we performed initial screening in >100 patients, typed 58 potential recipients and 85 donors, and identified 13 potential recipients (age ≥ 16 years) with matched sibling donors. Two were excluded because of major ABO incompatibility. Among the remaining 43, 10 patients who met all study criteria on full screening were selected for alternative donor searching. MUD search results identified a median of 2.5 (range 0–18) 6/6 HLA-matched donor available. Five individuals had 0, four had 4–6, and one had >15 potential donors. UCB search revealed no patient had a 6/6 HLA-matched, two had 15–16 5/6 HLA-matched, and five had 11–190 4/6 potential donor UCB units. The median UCB units containing ≥ 2 × 10e7 nucleated cells per kg were 0 for 6/6 HLA-matched (range 0–1), 0 for 5/6 HLA-matched (range 0–19), and 8.5 for 4/6 HLA-matched (range 0–190). When ethnic haplotype and allelic frequency, the available ABO status, the likelihood of requiring two UCB units for each adult recipient were considered, 5 had neither MUD nor UCB units available, 2 only had potential UCB units available, and 3 had both MUD and UCB units available. The majority of adults with severe SCD who are eligible for non-ablative allo-HSCT do not have matched sibling donors. Our search shows that the minority of African-American adults have potential alternative donors, 10% and 50% MUD and UCB, respectively. These numbers will likely be reduced when major ABO mismatches are excluded. Further, unlike pediatric patients, one cord blood unit may not provide sufficient cells to overcome the barrier of graft rejection in most adults. Given these limitations, the feasibility of haplo-identical family donor allo-HSCT should be investigated.

A Population-Based Study In Acute Myeloid Leukemia (AML) Suggests Improved Overall Survival (OS) up to Age 80 with Intravenous Therapy: 2000–2007 Data From the Surveillance, Epidemiology, and End Results (SEER)-Medicare Registry In the United States (US),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3589-3589
Author(s):  
Betul Oran ◽  
Daniel J. Weisdorf ◽  
Beth Virnig
Keyword(s):  
Treatment Group ◽  
Age Groups ◽  
Human Leukocyte ◽  
The United States ◽  
Population Based ◽  
Older Age ◽  
Hla Typing ◽  
Hypomethylating Agents ◽  
Intravenous Therapy ◽  
Hematopoietic Stem

Abstract Abstract 3589 Background: AML is the most common leukemia among US adults with median age of 69. Earlier 1990s studies reported a median OS was 2.4 months among patients older than age 65. Considering the trends in older AML treatment might have changed during the last decade, we investigated clinical practice for older AML patients. Methods: Patients age ≥ 66 in the National Cancer Institute's (NCI) SEER cancer registry with a first, primary cancer of AML diagnosed between January 2000 and December 2007 were matched to their Medicare Part A and Part B claims for long-term follow-up. Diagnostic evaluation and treatment patterns with disease outcomes were assessed. There were 4633 AML patients identified, and 1791(38.6%) received intravenous leukemia therapy within 3 months of diagnosis (treatment group). Treated patients then were sub-grouped as receiving chemotherapy (chemo) (94.9%) and hypomethylating agents (hypo) (5.1%). Results: The median age of the study population was 78. Treatment group had similar demographics compared to the no treatment group except they were younger (median age, 74 vs. 80, p<0.01) and more were male (56.9 % vs. 48.8%, p<0.01). Median Charlson comorbidity score (CCS) were similar (median, 0) but less patients in treatment group had CCS ≥ 2 (13.0% vs. 20.1%, p<0.01). Patients in treatment group received more extensive diagnostic work-up including: flow cytometry (72.3% vs. 50.8%, p<0.01), cytogenetics (48% vs. 27.4%, p<0.01) and human leukocyte antigen (HLA) typing (6.8% vs. 0.6%, p<0.01). Median OS was 3 months, but superior in the treatment group (7 mo. vs. 2 mo, p<0.01). This benefit was demonstrable in all age groups with greatest improvements in age 66–69 (10 mo. vs. 4 mo, p<0.01) and 70–74 (8 mo. vs. 3 mo, p<0.01) (Figure 1). Older age and CCS ≥2 were also associated with decreased OS (HR=1.04 (for each year), p<0.01 and HR=1.3, p<0.01 respectively). Within the treatment group, 2-month mortality after treatment was 31.2 % with the lowest level in age groups 66–69 and 70–74 (19.8 % and 25.2 %). Logistic regression analyses revealed that older age and CCS ≥2 were significantly associated with higher 2-month mortality (HR=1.08 (for each year), p<0.01 and HR=1.3, p<0.01 respectively). Among treated patients, a subgroup analysis of 91 patients receiving hypo showed that they were older than chemo group (median age 78 vs. 74, p<0.01), but had similar CSS scores. Although OS with hypo was increased compared to chemo group (9 mo. vs. 6 mo.) in multivariate analysis this difference was not significant (HR=1.25, p=0.07). Hematopoietic stem cell transplantation (HCT) was performed only in 57 patients (1.2%) after AML diagnosis. Median time to HCT after AML diagnosis was 6 months. These patients were younger (median age 66 vs. 73 in other treated patients) and none had CSS scores >2 (0% vs. 6.1%). Their median OS from diagnosis was 25 months. Conclusion: Intravenous therapy improves OS in older AML patients and most patients up to 80 years of age should be considered for treatment based on their comorbidity status. New therapies including hypomethylating agents and allogeneic HCT are promising and must be compared with other chemotherapy in the appropriately selected population. Disclosures: Weisdorf: Genzyme: Consultancy, Research Funding.

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

Blood ◽  
2007 ◽  
Vol 110 (13) ◽  
pp. 4576-4583 ◽  
Author(s):  
Stephanie J. Lee ◽  
John Klein ◽  
Michael Haagenson ◽  
Lee Ann Baxter-Lowe ◽  
Dennis L. Confer ◽  
...  
Keyword(s):  
High Resolution ◽  
Human Leukocyte ◽  
The United States ◽  
Disease Stage ◽  
Unrelated Donor ◽  
Hla Matching ◽  
Leukocyte Antigen ◽  
Donor Factors ◽  
Resolution Level ◽  
Program Data

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.

scholarly journals Charting Improvements in US Registry HLA Typing Ambiguity Using a Typing Resolution Score

2016 ◽  
Author(s):  
Vanja Paunić ◽  
Loren Gragert ◽  
Joel Schneider ◽  
Carlheinz Müller ◽  
Martin Maiers
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
The United States ◽  
Hla Typing ◽  
Data Sets ◽  
Hematopoietic Stem ◽  
Sequencing Technologies ◽  
Current State ◽  
Typing Methods

AbstractUnrelated stem cell registries have been collecting HLA typing of volunteer bone marrow donors for over 25 years. Donor selection for hematopoietic stem cell transplantation is based primarily on matching the alleles of donors and patients at five polymorphic HLA loci. As HLA typing technologies have continually advanced since the beginnings of stem cell transplantation, registries have accrued typings of varied HLA typing ambiguity. We present a new typing resolution score, based on the likelihood of self-match, that allows the systematic comparison of HLA typings across different methods, data sets and populations. We apply the typing resolution score to chart improvement in HLA typing within the Be The Match Registry of the United States from the initiation of DNA-based HLA typing to the current state of high-resolution typing using next-generation sequencing technologies. In addition, we present a publicly available online tool for evaluation of any given HLA typing. This typing resolution score objectively evaluates HLA typing methods and can help define standards for acceptable recruitment HLA typing.

High Impact of Human Leukocyte Antigen Matching On Overall Survival and Transplant Related Mortality in Allogeneic Hematopoietic Stem Cell Transplantation for CLL: Long-Term Study From the EBMT Registry.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2286-2286
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stéphane Morisset ◽  
Dietger Niederwieser ◽  
Vladimir Koza ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Resolution ◽  
Total Population ◽  
Human Leukocyte ◽  
Disease Status ◽  
Hla Matching ◽  
Low Resolution ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Unrelated Donors

Abstract Abstract 2286 Poster Board II-263 Background: The outcomes of related and unrelated donor hematopoietic stem cell transplantations (HSCT) are strongly affected by the degree of human leukocyte antigen (HLA) matching between the transplant recipient and the donor or cord blood unit. HLA matching plays an important role in engraftment, incidence and severity of graft-versus-host disease (GVHD) and also in overall survival; although this factor is still not validated yet in many hematological malignancies. Objective: To evaluate the impact of HLA matching and difference in matching degree among transplants from unrelated donors (UD) on different outcomes in chronic lymphocytic leukemia (CLL). Materials & methods: We have analyzed 370 CLL patients who underwent an allogeneic HSCT reported to the EBMT registry. There were 280 males (75%) and 90 females with a median age of 53 years (24-69). Forty-five patients (12%) have received a previous HSCT. At transplant, 294 among 317 evaluated patients had a good performance status (PS) (93%), 43 patients were in CR (12%), 160 in PR (46%), 44 in SD (13%) and 103 in PD (29%) among 349 evaluated patients. Two hundred and sixty six patients received a reduced intensity conditioning regimen (RIC) and 103 a standard (Std) conditioning; 313 patients received PBSC, 56 BM and 2 cord blood cells from 198 HLA siblings, and 172 unrelated donors (UD). There were 136 (36%) sex-mismatched (91 F/M and 45 M/F), 150 pairs (40%) had an ABO incompatibility (61 minor, 89 major) and for CMV: 78 pairs were +, 146 - and 111 mixed. The median interval between diagnosis and transplantation was 53 months (3-308). According to the registry, there were 198 HLA siblings, 135 matched UD (MUD) and 37 mismatched UD (MMUD). We focused on UD and re-analyzed all HLA typings for patients and donors, after classification we found: 24 well matched (10/10 in high resolution), 28 partially matched (7/7, 8/8 or 9/9 in high resolution), 30 matched in low resolution and 90 mismatched in high resolution, which was different from the registry classification. Results: After transplantation, 359 patients engrafted, 199 developed an AGVHD (gr I: 74, gr II: 79, gr III: 29 and gr IV: 17) and 171 presented a cGVHD (83 limited and 88 extensive). The cumulative incidence of AGVHD for the total population was 22% for gr II and 13% for gr > II. [Siblings: 19% and 12%; well & patially matched: 37% and 10%; low resolution & MMUD: 19.6% and 15.3% for grII & gr > II respectively]. At 1 year after transplant for the total population, the cumulative incidence of limited and extensive cGVHD was 17 % (15-19) and 18.4% (16.4-20.4)[ Siblings: 16.2% (13.6-19) and 17.2% (14.5-20); well & patially matched: 23% (17.2-29) and 23.1% (17.2-29); low resolution & MMUD: 15.8% (12.3-19.1) and 18.3% (14.8-21.8)] respectively. With a median follow up of 48 months, the probability of 3 and 5-years overall survival (OS) for the total population were 62% (56-67) and 52% (45-57) respectively. We found a high significant difference in term of OS between the siblings, well & partially matched groups versus low & MMUD groups (p=0.002) (figure 2). [OS at 3 & 5 years; Siblings: 68.3% (61.8-75.5) and 57.2% (49.8-65.6); well & patially matched: 60.8% (47.6-77.7) and 53.3% (39.2-72.4), low resolution & MMUD: 49% (40.3-59.5) and 38.5% (29.5-50.2) respectively]. We observed also a high significant difference in term of transplant related mortality (TRM) between the same groups (p=0.0022) (figure 4). The multivariate analysis using Cox model studying age, pre-transplant status; gender, PS, cells source, ABO compatibility, conditioning and different HLA groups, showed a significant impact of 4 factors on OS: age: HR=1.04 (1.01-1.6) p=0.001, disease status (PD): HR=3.08 (1.2-7.1) p=0.02, PS: HR=2.37 (1.1-5.1) p=0.02 and HLA MMUD group: HR= 1.62 (1.02-2.59) p=0.03. The same factors were also highly significant in multivariate analysis in term of TRM (age: HR=1.04 (1.001-1.07) p=0.009, disease status (PD): HR=5.49 (1.29-23.4) p=0.02, PS: HR=3.8 (1.7-8.4) p=0.01 and HLA MMUD group: HR= 1.9 (1.07-3.37) p=0.02. Conclusion: This large retrospective analysis pointed out the high impact of HLA matching in terms of OS and TRM (in addition of age, disease status and PS), without any difference between HLA siblings, MUD and partially matched groups. Moreover, we demonstrated the importance of HLA classification when registering patients in the EBMT registry and its impact on different outcomes. Disclosures: No relevant conflicts of interest to declare.

Outcomes of Patients Treated with Matched and Mismatched Unrelated Donors Using High-Resolution HLA Typing at 12 Loci

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3537-3537
Author(s):  
Stefan O. Ciurea ◽  
Rima M. Saliba ◽  
Gabriela Rondon ◽  
Poliana A. Patah ◽  
Morgani Rodrigues ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Resolution ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Disease Status ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Progression Rate ◽  
Hematopoietic Stem ◽  
Poor Risk

Abstract Abstract 3537 Donor-recipient HLA mismatches are associated with increased morbidity and mortality after UD hematopoietic stem cell transplants (HSCT). We hypothesized that HLA-DP mismatches would worsen outcomes of HSCT using donors mismatched at HLA-A,-B,-C,-DRB1 or -DQB1 and evaluated 391 consecutive patients (pts) with myeloid malignancies treated at our institution with 0,1,2,3 mismatches out of 12 alleles typed by high resolution at HLA-A,-B,-C,-DR,-DQ,-DP loci. Eighty-one pts were 12/12, 180 pts were 11/12, 113 pts were 10/12, and 15 pts were 9/12 HLA match with the recipients. Characteristics of the 4 groups (12/12, 11/12, 10/12, 9/12) were similar except source of stem cells; 87% of pts with 9/12 donors received bone marrow versus 60–62% for the other 3 groups. Results: Two-year overall survival (OS) and progression-free survival (PFS) were 40%, 44%, 45%, 53% and 33%, 40%, 44%, 49%, respectively (p=NS). However, OS was significantly worse with increasing number of mismatches for patients with AML/MDS with poor-risk cytogenetics (p=0.005, HR 1.6, 95% CI 2.1–4.2). Except for the 9/12 group, pts had a significantly higher non-relapse mortality (NRM) (11%, 24%, 36%) and lower risk of progression (32%, 25%, 20%). In the 9/12 group, NRM was 27% and progression rate was 40%. Grade II-IV, III-IV aGVHD as well as cGVHD were also progressively worse with increasing number of mismatches. Gr II-IV and III-IV aGVHD rates were 35%, 37%, 41%, 69%, and 8%, 8%, 15%, 16%, respectively. Cumulative incidence of cGVHD was 35%, 39%, 44% and 61%, respectively. Compared with 11–12/12 donors, pts who received a 9–10/12 donor had significantly higher rates of gr III-IV aGVHD and cGVHD (p=0.03, HR 2.1, CI 1.1–3.7 and p=0.02, HR 1.5, CI 1.1–2.1, respectively). Univariate analysis revealed that there is less NRM with a 12/12 donor (vs. other) (p=0.008, HR 1.9, 95% CI 1.2–2.9), while in multivariate analysis, compared with a 12/12 donor, the use of a donor with mismatch was significantly associated with higher NRM [HR and 95%CI were 2.1 and 1.04–4.4 for 11/12 donor (p=0.04); 3.1 and 1.5–3.3 for 10/12 donor (p=0.003); 2.8 and 0.9–9.3 for a 9/12 donor (p=0.08), respectively] (Figure). In multivariate analysis, factors significantly associated with OS were disease status at transplant (active disease vs. not) (p<0.001), cytogenetics for AML/MDS pts (poor-risk vs. other) (p=0.006, HR) and the use of fludarabine and busulfan conditioning (Bu 130mg/m2 × 4 days and Flu vs. other) (p=0.04, HR 0.7, CI 0.5–0.98), while factors significantly associated with NRM were, in addition to degree of mismatch, disease status at transplant (p=0.008, HR 1.9, CI 1.2–3.1) and use of BuFlu conditioning (p=0.004, HR 0.5, CI 0.4–0.8). In conclusion, these results suggest that, using 12/12 high-resolution HLA typing, a progressively higher NRM is encountered for unrelated donor pts with higher number of mismatches, at least in part related to higher rates of GVHD. Matching at DP loci appears to be protective of NRM and is associated with improved survival for patients with AML/MDS with poor-risk cytogenetics. Disclosures: No relevant conflicts of interest to declare.

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