A single high‐resolution HLA mismatch has a similar adverse impact on the outcome of related hematopoietic stem cell transplantation as a single low‐resolution HLA mismatch

Abstract

The relative importance of the resolution level of HLA typing has not been fully defined for related donor transplantation. To address this question, we retrospectively evaluated patients who underwent a first related hematopoietic stem cell transplantation (HSCT) from 2000 to 2011 from an HLA high‐resolution matched (MRD, n = 2,244), high‐resolution 1 locus‐mismatched (HR‐MMRD, n = 116), or low‐resolution 1 locus‐mismatched related donor (LR‐MMRD, n = 396) in the graft‐versus‐host direction at three loci (HLA A, B, and DRB1) using the database of the Japan Society for Hematopoietic Cell Transplantation. The median age was 40 years (0–74). The median follow‐up duration of surviving patients was 950 days. Although the cumulative incidences of grade III–IV acute graft‐versus‐host disease (GVHD) in the HR‐MMRD and LR‐MMRD groups were significantly higher than those in the MRD group (HR‐MMRD 19.8%, LR‐MMRD 20.4%, and MRD 9.5%), there was no statistically significant difference between the HR‐MMRD and LR‐MMRD groups (P = 0.65). Although both HR‐MMRD and LR‐MMRD were significantly associated with an increased risk of non‐relapse mortality and a worse overall survival, there was no statistically significant difference between the HR‐MMRD and LR‐MMRD groups. In conclusion, LR‐MM and HR‐MM have a similar adverse impact on the outcome in related HSCT. Am. J. Hematol. 90:618–623, 2015. © 2015 Wiley Periodicals, Inc.

High-Resolution HLA Typing of HLA-A, -B, -C, -DRB1, and -DQB1 in Kinh Vietnamese by Using Next-Generation Sequencing

“…Recently, it has been shown that both high-resolution HLA typing and haplotyping are important in hematopoietic stem cell transplantation for both unrelated and related donors in reducing post-transplantation adverse outcomes (Agarwal et al, 2017;Buhler et al, 2019); a single high-resolution HLA mismatch may lead to a similar negative effect on outcomes as a low-resolution one (Fuji et al, 2015;Armstrong et al, 2017). Therefore, it has been suggested that highresolution HLA typing can reduce the likelihood of missing a clinically significant mismatch compared to traditional lowresolution typing, especially in developing countries where highresolution HLA typing methods are not widely available (Agarwal et al, 2017).…”

Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation

“…The standard pharmacological GVHD prophylaxis regimen for HLA‐matched unrelated (MUD) or related donor (MRD) HCT includes a calcineurin inhibitor (commonly tacrolimus or ciclosporin) and methotrexate (Nash et al , ; Hiraoka et al , ; Perkins et al , ; Saber et al , ). This is often intensified with in vivo T‐cell depletion (TCD), generally with antithymocyte globulin (ATG) or alemtuzumab in MMUD HCT (Finke et al , ; Ayuk et al , ; Devillier et al , ; Fuji et al , ). With this intensive regimen, the incidence of grade II–IV acute GVHD (20–35%), grade III–IV acute GVHD (4–20%) and chronic GVHD (22–67%) in MMUD HCT approaches comparable levels to those seen after MUD HCT (Finke et al , ; Ayuk et al , ; Kim et al , ; Devillier et al , ; Fuji et al , ).…”

“…This is often intensified with in vivo T‐cell depletion (TCD), generally with antithymocyte globulin (ATG) or alemtuzumab in MMUD HCT (Finke et al , ; Ayuk et al , ; Devillier et al , ; Fuji et al , ). With this intensive regimen, the incidence of grade II–IV acute GVHD (20–35%), grade III–IV acute GVHD (4–20%) and chronic GVHD (22–67%) in MMUD HCT approaches comparable levels to those seen after MUD HCT (Finke et al , ; Ayuk et al , ; Kim et al , ; Devillier et al , ; Fuji et al , ). However, in vivo TCD delays T‐cell immune reconstitution (Small et al , ; Duval et al , ; Bosch et al , ) and poses heightened risk of bacterial and viral infections, including herpes simplex virus, cytomegalovirus (CMV), Epstein–Barr virus, and infection‐related deaths (Bacigalupo et al , ), as well as fatal post‐transplant lymphoproliferative disorder (PTLD) (Small et al , ; van Esser et al , ; Finke et al , ).…”

Hidden genomic MHC disparity between HLA-matched sibling pairs in hematopoietic stem cell transplantation

“…The role of allelic mismatching at HLA-DPB1 in HSCT appears to be complex as it is related to expression level 23 and so called permissive and non-permissive mismatch groups 22 , 27 , 28 . It is also known that even a single allelic mismatch at HLA can induce an alloimmune response 29 , 30 , including graft-versus-leukemia effect, a favourable phenomenon that reduces the risk of relapse 31 , 32 . Hence, our finding that the number of mismatched nucleotides correlates with the GvHD risk fits well to these findings.…”