The French unrelated stem cell donors registry is an operational entity developping bone marrow donation and transplantation. Its national role is linked to that of its international counterparts. Under public law in France, it is managed by the biomedicine agency.

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 10 7 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7–90.7) and 79.3% (72.6–86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5–35.1) and 34.3% (27.0–43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.

In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.

Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for acute myeloid leukemia. In the absence of an HLA-matched related or unrelated donor (MRD or MUD), the best alternative donor source remains controversial. Umbilical cord blood and haploidentical donors offer a shorter delay from indication to transplantation. This retrospective multicentre study of a French registry compares overall survival in the 18 months following registration in the absence of a MRD between four types of donors. Between 2012 and 2016, 1302 patients were transplanted using MUD (control, n = 803), mismatched MUD (n = 219), umbilical cord blood (n = 153) and haploidentical (n = 127) donors. Multivariate analyses were conducted for overall survival after registration, after transplant, and transplant-related mortality. After adjustment for variables, the type of donor did not influence any of the three end points. Our results confirmed the significant negative impact of longer time between registration and transplant: HR = 1.04 [1.02–1.06] (p < 0.0001). This indicates a positive correlation between better survival and shorter registration-to-transplantation wait time. In the absence of a sibling donor, the alternative stem cell source does not impact early survival in acute myeloid leukemia patients. The minimization of registration-to-transplantation time should be considered when weighing the alternative donor options.

In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch®" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch®, demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p<0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p<0.0001). EasyMatch® estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification.

Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and the Societe Francophone d’Histocompatibilite et d’Immunogenetique (SFHI)

We have estimated human leukocyte antigen (HLA) haplotype frequencies using the maximum likelihood mode, which accommodates typing ambiguities. The results of the frequency distribution of the 7015 haplotypes obtained are presented here. These include a total of 114 HLA-A, 185 HLA-B, and 76 HLA-DRB1 unique alleles at each locus. Across all populations, although the most common individual HLA alleles were HLA-A∗02:01 (29.0%), HLA-B∗07:02 (11.4%), and HLA-DRB1∗07:01 (15.9%), the most frequent haplotype was found to be HLA-A∗01:01∼B∗08:01∼DRB1∗03:01.

High-resolution haplotype frequency estimations and descriptive metrics are becoming increasingly popular for accurately describing human leukocyte antigen diversity. In this study, we compared sample sets of publically available haplotype frequencies from different populations to characterize the consequences of unequal sample size on haplotype frequency estimation. We found that for low samples sizes (a few thousand), haplotype frequencies were overestimated, affecting all descriptive metrics of the underlying distribution, such as most frequent haplotype, the number of haplotypes, and the mean/median frequency. This overestimation was a result of random sample fluctuation and truncation of the tail end of the frequency distribution that comprises the least frequent haplotypes. Finally, we simulated balanced datasets through resampling and contrasted the disparities of descriptive metrics among equal and unequal datasets. This simulation resulted in the global description of the most frequent human leukocyte antigen haplotypes worldwide.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. The main aim of this session was to describe the relations between the national transplant coordination office of the French registry and local stem cell transplantation coordinators throughout France.

In order to study the impact of human leucocyte antigen (HLA) polymorphism distribution in identifying a matched haematopoietic stem cells unrelated donor (UD), we performed a multi-centric retrospective analysis with the aim of comparing the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 phenotypes of 2126 patients (772 patients for whom a donor search failed to identify a matched UD, and 1354 patients who received a 10/10 allele level matched UD). Our results showed that rare HLA-C is often responsible for difficulty in identifying a donor. This locus may add a degree of complexity to a supposed 'frequent' HLA-A HLA-B and HLA-DRB1 phenotype, turning this phenotype into a less frequent one. For example, 32.5% of the phenotypes in the non-transplanted patients could not be explained by any of the pairs of known HLA-A, HLA-B, HLA-C and HLA-DRB1 haplotypes while this percentage dropped to less than 2% if combinations of only HLA-A, HLA-B and HLA-DRB1 haplotypes were considered. Such situations can be anticipated by computing an index, based on HLA haplotype frequency, the average registry sample size (ARS). ARS is defined as the inverse of the phenotype frequency computed using all corresponding pairs of haplotype frequencies. ARS confirmed that the most significant difference between transplanted and non-transplanted patients was correlated with the introduction of the locus HLA-C in the analysis (median: 8.3e + 4 vs 3.1e + 6, P < 0.0001). The higher the ARS the lower the likelihood of finding a 10/10 match UD reflecting the rareness of the patient's HLA. The area under receiver operator characteristics (AUROC) values of the ARS computation for HLA-A, HLA-B and HLA-DRB1 was 0.82 (0.80; 0.84) at a low-resolution level (two digits). Overall, our study promotes the use of haplotype frequency-based computations to develop computer-assisted donor search.

The European Group for Blood and Marrow Transplantation (EBMT) risk score provides a simple tool to assess chances and risks of hematopoietic stem cell transplantation (HSCT) for an individual patient from related and unrelated donors. To our knowledge, this score has never been applied in double umbilical cord blood transplantation (dUCBT). We recently published results of 136 patients who underwent dUCBT reported to the SFGM-TC registry from 23 centers between 2005 and 2007 (Labussiere et al., Exp. Hem. 2013). After having recorded the full data on CB units including HLA and sex, we decided to test the validity of the EBMT risk score and check its application in dUCBT. There were 88 males and 48 females with a median age of 41 years (range: 18 – 66), 76 patients with acute leukemias (42 AML, 27 ALL, 5 secondary AL and 2 Biphenotypic AL), 8 with chronic leukemias (5 lymphoid and 3 myeloid), 10 with myelodysplasic syndormes, 24 with Hodgkin and non Hodgkin lymphomas, 13 with multiple myelomas and 5 with other myeloproliferative diseases. Median interval between diagnosis and transplantation was 20.5 months (range: 3-385). At time of allogeneic transplantation, 41 patients were in first complete remission (CR1), 40 in ≥CR2 and 55 less than CR. Forty-six patients received myeloablative and 90 reduced intensity conditioning regimens. The EBMT risk score uses the 5 pre-transplant factors: age of the patient, disease status, time from diagnosis to transplant, kind of donor (related/unrelated), and donor-recipient sex combination with 0 to 1 or 2 points (pts) for each factor. Age was categorized as 40 years (2 pts; n=71). For disease status we distinguished patients in CR1 at transplantation, (0 pt; n=41) from patients in CR >1 (1 pt; n=40) and patients not in CR (2 pts; n=55). Time from diagnosis to transplant was categorized into ≤12 months (0 pt; n=26) and >12 months (1pt; n=110). The adaptation of the new risk score concerned HLA and sex matching. Complete information concerning HLA typing was obtained from the database of the national network of cord blood banks on behalf of Eurocord. HLA typing was evaluated across 3 loci: HLA-A, -B and -DRB1; it was based on antigenic level for HLA-A and HLA-B, and on allelic level for HLA-DRB1. HLA matching showed patients with at least 4/6 HLA matching on HLA-A, -B and DRB1 without any mismatch on DRB1 alleles between the recipient and each UCB unit and the 2 units together (0 pt; n=77); patients with at least 4/6 HLA matching on HLA-A and -B between the recipient and each unit but without complete matching on DRB1 or with less than 4/6 HLA matching between the 2 units (1 pt; n=51), and finally patients with more than 2 mismatches on the three loci (2 pts; n=8). Donor-recipient sex combination separated all others (0 pt; n=73) from the male recipient with one female and one male cord blood unit (1pt; n=45) and male recipient with two female cord blood units (2 pts; n=18). Hence, we found 5 patients (4%) in score 1, 12 (9%) in score 2, 23 (17%) in score 3, 26 (19%) in score 4, 30 (22%) in score 5, 26 (19%) in score 6, 11 (8%) in score 7 and 3 (2%) in score 8. We pooled patients with scores 1-2; 3-4 and 5-8 as their outcomes were found to be similar. After a median follow-up of 49.5 months, the 3 years probabilities of overall and progression-free survivals for the whole population were 41% and 35% respectively. with a two-year cumulative relapse incidence of 28% (24.0 – 31.8). Interestingly patients with score 1-2 showed better overall survival rates than those with score 3-4 and 5-8 with a 3 years probability of 77%, 42% and 32% respectively (p=0.002); this was associated with a 3 years relapse incidence of 19%, 35% and 55% respectively (p=0.021), while the 3 years transplant related mortality (TRM) was 6%, 39% and 36% respectively (score 1-2 versus all others, p=0.02), Figure 1. In conclusion, we found that the EBMT risk score can perfectly be applied to double UBCT with a significant impact on different outcomes; its use enables a better selection of patients who will benefit the more from this treatment strategy. Disclosures: No relevant conflicts of interest to declare.

Austrian transplant centers (TC) send in MED-A reports on all transplants quarterly due to national competent authority requirements. We analyzed the quality of data reported to the Austrian Stem Cell Transplantation Registry (ASCTR) from 2000 to 2011 regarding diagnosis and disease status. Main diagnosis was reported in 100% of transplants (n=4766). According to subclassifi cations of main transplant indications, 0.9 % of overall lymphomas (n = 1061), 3% of B-cell lymphomas (n=703), 87% of diff use large B-cell lymphomas (n=336) and 7% of T-cell lymphomas (n=123) were not further specifi ed. Only 0.4% solid tumors (ST, n = 498) miss a subclassifi cation. For acute leukemia (AL, n = 1078) diff erentiation into AML, ALL and others was available in all patients. Two and 5% of primary AMLs (n = 610) and ALLs (n= 344) are without further subclassifi cation. In plasma cell disorders (PCD, n = 1425) subdivision into myeloma (MM) and other types is complete. Within MM (n=1383) information on light chain only, or heavy and light chain is missing in 0.4% whereas in 17% of patients with heavy and/or light chain MM the distinction between λ or κ is missing. Chronic leukemias (CL, n=203) had complete information on the subcategories chronic myeloid leukemia (CML, n=137), chronic lymphocytic leukemia (CLL, n=63) and chronic prolymphocytic leukemia (CPL, n=3). However, in CLL 12% had no further subclassifi cation. Then, we analyzed the reporting of disease status at transplant (n=4554) for the above mentioned indications plus for secondary AL, myelodysplastic syndrome, myeloproliferative neoplasms (sAL/MDS/MPN). On average in 3% this information is missing with a range from 0.7% (AL) to 10% (ST). Regarding best response data after transplant 18% (sAL/MDS/MPN) to 30% (ST) are missing. Information on disease status at last reported followup (FU) for patients reported ‘alive’ and having a FU > 100 days (n= 2154) is missing in 35%, showing a remarkable range from 17% (sAL/MDS/MPN) to 86% (CL). Summary: There are reporting diff erences between disease groups which need detailed investigation. Further eff orts are necessary to achieve complete best response and disease status data at FU in all patients. Support to transplant centers reporting a constantly growing number of patients is warranted to improve quality. We would like to thank all individuals providing data to the ASCTR and colleagues in the EBMT data offi ces for their support.