The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure

202

201

A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSAcorresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P ¼ 0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.

Section: Patientsmentioning

confidence: 99%

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT

Yoshihara

Maruya²,

Taniguchi

et al. 2011

202

201

“…The incidence of graft failure is assumed to range from 2 to 20%, and the frequency depends on various factors such as stem cell source 1,2 and preconditioning regimen, [3][4][5] underlying disease, 5 HLA disparity 2,6,7 and the presence of anti-HLA Abs. 8 Salvage HSCT can rescue pGF patients, [9][10][11][12][13][14] and recent studies on adult pGF patients have showed the feasibility of using reduced-intensity conditioning containing fludarabine (FLU) and low-dose irradiation, 13,[15][16][17] including short-term preconditioning regimen 10,18 and an advantage of PBSC as the stem cell source for salvage HSCT. 19,20 However, the management of pGF patients is usually difficult because of their poor clinical status.…”

Section: Introductionmentioning

confidence: 99%

Salvage allogeneic hematopoietic SCT for primary graft failure in children

Kato

Matsumoto²,

Suzuki

et al. 2013

Primary graft failure (pGF) is associated with considerable morbidity and mortality. Salvage hematopoietic SCT (HSCT) can rescue pGF patients; however, the optimal preconditioning regimen and stem cell source are yet to be determined, particularly in children. In this study, we retrospectively analyzed 102 pediatric patients who received salvage allogeneic HSCT for pGF. Salvage HSCT from matched or one-Ag-mismatched related donors (rMM01) provided superior OS compared with that from two-or three-Agsmismatched related donors (rMM23) or cord blood transplantation (CBT). CBT showed a trend toward a slightly lower engraftment rate and late engraftment achievement compared with rMM23; however, the OS rate was similar between the two groups (47.6 ± 7.7% for rMM23 and 45.7 ± 8.6% for CBT, at 1 year after salvage HSCT). Multivariate analysis showed that preconditioning regimens with fludarabine or irradiation were associated with a higher engraftment rate and those with alkylating agents were associated with better OS. In conclusion, our results showed that rMM01 was the most suitable donor for salvage HSCT for pediatric pGF, and that CBT was an equally important option compared with rMM23 for patients without rMM01.

“…18 Recipient antibodies against mismatched donor HLA-DP have also been shown in 10/10 matched MUD alloSCT to be associated with a higher incidence of graft failure and mortality. 19 Risk of rejection also increases with increasing numbers of mismatches at HLA-A, -B, -C and -DR loci. 20 Patients receiving dUCBT often have a period of transient mixed chimerism and almost universally have eventual dominance of one cord and disappearance of the other.…”

mentioning

confidence: 99%

Umbilical cord blood graft engineering: challenges and opportunities

Thompson

Rezvani

Hosing

et al. 2015

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specificT-cells or chimeric-antigen receptor T-cells which are reviewed in this study.