The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing Xgrade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of Xgrade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.

Previously, we showed that with an increasing number of amino acid differences in single HLA class I-mismatched molecules, the probability of T cell alloreactivity decreases. It is unlikely that every amino acid difference will affect T cell alloreactivity in a similar way; we hypothesized that the effect of an amino acid difference may be dependent on its position and/or physicochemical properties. We selected 131 patient/donor pairs with either a single HLA-A or -C mismatch in the graft-versus-host direction and that were compatible for HLA-B, -DRB1, and -DQB1. The alloreactive CTL precursor (CTLp) frequency was determined and associated with the amino acid differences between the single HLA class I mismatches. In the β sheet, only amino acids that are noncompatible in their physicochemical properties affect T cell alloreactivity, whereas in the α helices, both compatible and noncompatible amino acids affect CTLp outcome. Positions 62, 63, 73, 76, 77, 80, 99, 116, 138, 144, 147, and 163 were bivariately associated with CTLp outcome, irrespective of the total number of amino acid differences. In multivariate analysis, positions 62, 63, 73, 80, 116, 138, 144, and 163 were found to be most predictive for negative CTLp outcome. These results formed the basis for a weighted predictive mismatch score; pairs with the highest mismatch scores are estimated to be 13 times more likely to have a negative CTLp. This new algorithm may be a tool in donor selection for hematopoietic stem cell transplantation.

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We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n = 171) and 10/10 HLA-A-, -B-, -C-, -DRB1-and -DQB1-matched grafts (n = 168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾ grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLAmismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.

The Cord Blood Working Group of the World Marrow Donor Association created a survey for cord blood banks (CBBs) aimed to identify and understand the main technical procedures currently used by public CBBs worldwide regarding cord blood units (CBUs) available for unrelated hematopoietic stem cell transplantation. These technical procedures include CBU collection, (pre-) processing, packaging, testing, storage and transport. The survey was an online survey created with SurveyGizmo and was completed individually by each CBB at the end of 2017. The information is valuable to transplant centers, CBBs as well as the global industry of public cord blood banking. In general, we can conclude from this survey that the majority of CBBs are up to standard in terms of CBB technologies. Areas of improvement include accreditation, increase standardization in testing and setting of total nucleated cells thresholds for acceptance a CBU for public use. Furthermore, there is a need for a consensus in the way CBBs operate in term of reservation and release to facilitate a more straightforward access to the therapy. K E Y W O R D S cord blood banks, cord blood units, public cord blood banks, unrelated hematopoietic stem cell transplantation

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To investigate whether all patients in need of an allogeneic hematopoietic SCT (HSCT) are offered one, we retrospectively investigated the policy for all children diagnosed with myelodysplastic syndrome (n=90) or relapsed AML (n=75) between 1998 and 2008. These children are registered at diagnosis and treated according to protocols of the Dutch Childhood Oncology Group, which provides accurate disease incidence data and protocol-indicated appropriateness for HSCT. For 48 (30%) patients, a family donor was identified; for 90 (57%) patients, an unrelated donor (UD) search was performed; and for 21 (13%) patients, no UD search was initiated. Reasons for not initiating an UD search include: progressive disease (n=10), conserve quality of life (n=1), stable disease (n=3), immunosuppressive therapy (n=2), patient death (n=3), patient lives abroad (n=1) and second relapse (n=1). On the basis of the time interval between date of diagnosis and date of death/last follow-up, for eight (5%) patients, it may be questioned why an UD search was not performed. The fact that 95% of all children are given the option of an allogeneic HSCT is encouraging and reasons not to transplant seem fair in most cases.