Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

Abstract

Summary The relevance of donor‐specific human leukocyte antigen (HLA) antibodies in HLA‐mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA‐matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi‐centre study. Pre‐HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA‐matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7·5, P = 0·028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel‐reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft‐versus‐host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0·011. Pre‐HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA‐matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.

The impact of pre-existing HLA and red blood cell antibodies on transfusion support and engraftment in sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation from HLA-matched sibling donors: A prospective, single-center, observational study

“…Furthermore, HLA alloimmunization was not associated with any adverse engraftment outcome or GVHD in this study. These results are in contrast with our previous results in pediatric myeloablative HSCT for SCD where HLA alloimmunized patients had a higher incidence of acute GVHD [17]. This apparent inconsistency is reflective of the very different conditioning as no GVHD was observed with this nonmyeloablative regimen.…”

“…The association between HLA class I alloimmunization and increased platelet transfusion support has been reported in the myeloablative HSCT setting where children with SCD commonly receive greater than 10 platelet transfusions [17]. We now confirmed this same association in the nonmyeloablative setting in adults who, however, received a median of only 1 platelet transfusion.…”

Effect of serum panel reactive antibodies on allogeneic hematopoietic stem cell transplantation in pediatric thalassemia patients: A single‐center experience

“…Considering that HLA class I is also present on human platelets, alloimmunization against HLA class I can result in platelet transfusion refractoriness. Although this issue may be relevant to all HSCT patients, it holds particular significance for individuals with hemoglobinopathies undergoing HSCT 21 . These patients often require numerous platelet transfusions while waiting for donor engraftment to maintain adequate platelet counts.…”

Aloimunização eritrocitária e HLA em doença falciforme

“…Assim, da mesma forma que polimorfismos nos genes HLA-B, HLA-DR, IL-4, CD40L, FcGR2A e TNF foram relacionados à resistência à malária, outros polimorfismos genéticos relacionados à resposta imune poderiam ter relação com a maior predisposição à aloimunização na DF(103). (110).…”

“…A associação entre aloimunização HLA e eritrocitária é descrita tanto em pacientes com DF como em pacientes com outras doenças (111,112,190). É possível que a elevada prevalência de aloimunização (110). Os autores sugerem que o paciente aloimunizado, e, portanto, respondedor imune, desenvolve uma resposta imunológica diferenciada que deve envolver APCs mais eficazes em estimular a resposta de células T contra antígenos eritrocitários e HLA, assim como em ativar a resposta de células T de doadores contra o receptor (110).…”