List of recommendations• All laboratories performing H&I testing for allogeneic HPC transplantation should follow EFI standards and be accreditated by EFI and UKAS/CPA. (Grade 1A)• HLA typing definitions as described by Nunes et al. 2011 and here should be used (Grade 1A)• HLA typing results should use official WHO HLA Nomenclature (Grade 1A)• The clinical urgency should be made available to the individual performing the related and unrelated donor search (Grade 1B)• HLA high resolution typing should be performed on potential matching; mismatching and haploidentical related donors when familial haplotypes cannot be fully assigned (Grade 1A)• Patients and selected related donors should be typed for HLA-A, -B, -C, -DRB1 and -DQB1 (+/-DPB1) (Grade 1A).• All patients and donors must have their HLA type confirmed on a second sample pre-transplant (Grade 1A).• The patient should be high resolution typed prior to submitting the HLA type for an unrelated donor search (Grade 1A)• A 10/10 high resolution HLA-A, -B, -C, -DRB1 and -DQB1 matched unrelated PBSC or bone marrow donor should be used where possible (Grade 1A).• Where a 10/10 matched PBSC or bone marrow donor is not available a single mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 is acceptable (Grade 1A).• Alternative progenitor cell donors (cord blood or haplo-identical) should be considered early in the donor search when a patient is unlikely to have an HLA matched unrelated donor (Grade 1A).• HLA-DRB3, -DRB4, -DRB5 typing should be performed and, when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, mismatches for these should be minimized (Grade 2A). • For unrelated donor selection, HLA-DPB1 typing should be performed and when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, non-permissive mismatches should be minimised (Grade 2C).• For mismatched related and unrelated donor selection, HVG mismatches are favoured over bi-directional and GVH mismatches (Grade 2C).• UCB units should be HLA typed to high resolution HLA-A, -B, -C, -DRB1, -DQB1 (Grade 1B ).• Selection of UCB units should follow national consensus guidelines published by Hough et al. (Grade 1A).• HLA alloantibody testing of the recipient should be performed at the time of donor search and should be repeated at the time of donor work-up request if an HLA mismatched donor is selected (Grade 1A).• The clinical team must be made aware of any HLA alloantibody incompatibility for a selected donor (Grade 1A).• When a choice of equally well matched donors is available, avoid selection of donors against which the patient has HLA alloantibodies (Grade 1A).• HLA alloantibody testing should be performed in cases of failed engraftment if the donor is HLA mismatched (Grade 1B).• The guideline published by Emery et al., 2013 recommending CMV matching between patient and donor should be followed (Grade 1A).• Major ABO incompatibilities should be avoided when there is a choice of HLA and CMV matched donors (Grade 1A)• Male donors ...
Since 2000, Quality Assurance (QA) exercises for the detection and identification of granulocyte antibodies and DNA typing for human neutrophil antigens (HNA) have been distributed within the International Granulocyte Immunobiology Workshops, which are linked to International Society of Blood Transfusion. The exercises were standardised at the outset to enable laboratory performance to be monitored. Between 2000 and 2012, nine exercises were distributed to 20 laboratories. Overall, 45 examples of 42 unique samples containing defined granulocyte reactive antibodies were distributed for serological analysis together with 20 samples for HNA genotyping. The level of satisfactory serological performance was initially set at 50% and later increased to 70%, while the 'cut-off' for HNA genotyping was set at 100% after 2008. Failure to achieve the minimum score in the QA exercises in consecutive years resulted in temporary exclusion. In 2000, the 15 participating laboratories had a mean score of 56.1% for serological analysis and 13 laboratories attempted HNA-1a and -1b genotyping, while 11 attempted HNA-1c typing. Steady improvements in proficiency for serological testing and HNA typing occurred in subsequent exercises. In 2012, the mean score for serology was 88.5% and 12/13 laboratories scored 100% for HNA-1a, -1b, -1c, -3a, -3b, -4a, -4bw, -5a and -5bw genotyping. These QA exercises have provided an invaluable tool to monitor and improve the standard of granulocyte immunology investigations for participating laboratories, thereby enhancing performance for both clinical investigations and donor screening programmes to reduce the incidence of TRALI.
Umbilical cord blood (UCB) is an important source of stem cells for transplantation and may cause less GvHD than non‐T‐depleted bone marrow (BM). Only 25% of paediatric patients have an HLA matched sibling and for the remainder an unrelated BM or UCB donation may also not be available. A directed UCB (DCB) collection from a newborn sibling may be the only opportunity for a transplant until the sibling can donate BM. Matched DCB donations have been shown to give better long‐term results than matched unrelated UCB or BM but DCB collection is not as easy to control as unrelated banking in hospitals established as collection sites. In the context of mandatory licensing under the European Union Tissues and Cells Directive introduced in April 2006, we have reviewed NBS DCB banking. Over ten years, 268 DCB collections were made, 233 (87%) for an existing sibling with a disease treatable by transplantation, and the remainder for families with a history of an inherited high risk disease. Diagnoses included 114 haematological malignancies, 68 hereditary anaemias and 53 immune or metabolic deficiencies. Collections were cryopreserved within 24 h without volume reduction. Volume mL Total TNC ×108 Total CD34 ×106 TNC Viability % Median738.82.399.0Mean ± S.D.76 ± 329.9 ± 5.53.3 ± 3.498.2 +3.7Range14–1731.0–31.00.13–26.773.0–100.0 88% of collections exceeded 40 ml UCB, the cut‐off used by some banks including NHS‐CBB. Despite the logistical difficulties in organising collections from many hospitals the cell counts and viabilities of DCB collections compare favourably with collections for UCB banks. The decision to continue storage was made once the cell counts and tissue typing results were also known. Of units collected for existing siblings, 67 (28%) were a 10:10 match for HLA ‐A, ‐B, ‐Cw, ‐DRB1 and ‐DQB1. Of these, 13 units were transplanted, with 10 for non‐malignant disorders, including one collected following pre‐implantation tissue typing for a sibling affected by DBA. Median time to neutrophil engraftment was 18 days (range 14–28) and 30 days (range 11–59) for platelets. DCB collection provides the option of immediate transplant with the potential of future sibling donation of stem cells or lymphocytes. DCB banking for high‐risk families is therefore a useful service to provide and complements the work of unrelated UCB banks.
Microsatellite analyses show that self-reported ethnicity often correlates poorly with true genetic ancestry. As unknown ancestral differences could potentially have an impact on transplant outcome, we developed an average allele length discrepancy (AALD) score to assess allele length discrepancy between donor/recipient (D/R) using microsatellites analysed routinely in post-transplant chimeric assessment. This was then compared with outcome in a homogeneously treated cohort of pediatric patients undergoing high-resolution sibling or matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL). AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for sibling pairs and 0.8-2.17 (median 1.6) for high-resolution matched unrelated donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score, which reached statistical significance above a threshold of 1.7 for OS. Patients whose transplants had an AALD score of ⩾ 1.8 had a risk of non-relapse mortality 4.9 times greater (P = 0.025) and relapse risk three times greater (P = 0.058) than those scoring o 1.8. This approach will now be explored in a Centre International for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs across all disease groups; if confirmed, it has the potential to improve donor selection for patients with multiple prospective donors.
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