The impact of anti-HLA antibodies on unrelated cord blood transplantations

Takanashi, Minoko; Atsuta, Yoshiko; Fujiwara, Koki; Kodo, Hideki; Kai, Shunro; Satō, Hiroyuki; Kohsaki, M; Azuma, Hiroshi; Tanaka, Hidenori; Ogawa, Atsuko; Nakajima, Kazunori; Kato, Shingo

doi:10.1182/blood-2009-10-249219

Cited by 222 publications

(176 citation statements)

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“…BM chimerism on day þ 30 of these cases showed a median of 100% of CB cells (range 75-100%). Median time to neutrophil engraftment in this group was 19 days (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Standard Engraftment Group (N ¼ 14)mentioning

confidence: 99%

“…[13][14][15] From the extensive experience with CB transplantation, various risk factors have been associated with CB graft failure. [16][17][18] Once transplantation has been performed, early detection of graft failure is important to start rapid therapeutic measures such as immunomodulation and to launch a second transplant when appropriate as soon as possible. With this objective, chimerism studies performed in the early post-transplant period have been shown to facilitate prediction of engraftment outcome in different allogeneic SCT settings including CB SCT.…”

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confidence: 99%

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Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

Kwon

Martínez-Laperche

Balsalobre

et al. 2013

Bone Marrow Transplant

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Single-unit umbilical cord blood (CB) SCT is limited by low total nucleated cell (TNC) dose. Co-infusion of CD34 þ cells from a third party HLA-mismatched donor, known as dual or haplo-cord transplant, reduces the period of post-transplant neutropenia and related complications. The aim of this study was to analyze the value of early post-transplant peripheral blood (PB) and T cell chimerism after 28 dual transplants regarding CB engraftment. Cumulative incidence of myeloid engraftment at 30 days was 93% with a median time to engraftment of 14 days (10-29). Patients who developed CB graft failure (n ¼ 5) showed very low percentages of CB cells on days þ 14, þ 21 and þ 28 with decreasing dynamics. On the other hand, percentages of CB cells in patients who achieved CB engraftment increased over time. Interestingly, such patients showed two distinct chimerism dynamics in PB, but all of them showed a predominance of CB T cells early after SCT with increasing dynamics over time. Early post-transplant chimerism dynamics in PB and T cells predicts CB graft failure enabling rapid therapeutic measures to be applied. On the other hand, early increasing percentages of CB T cells correlates with ultimate CB engraftment.Bone Marrow Transplantation (2014) 49, 212-218; doi:10.1038/bmt.2013.177; published online 11 November 2013Keywords: cord blood transplantation; haploidentical donor; chimerism; graft failure INTRODUCTION Unrelated umbilical cord blood (CB) has been increasingly used as an alternative stem cell source for adult patients eligible for allogeneic SCT, but lacking HLA-matched adult donors. [1][2][3] However, one of the main limitations of CB transplantation is the late engraftment related to low total nucleated cell (TNC) dose, with the subsequent increased risk of serious early neutropenia-related infections and high non-relapse mortality. 2,4 Single CB transplantation supported by mobilized and selected CD34 þ cells from a HLA-mismatched third party donor (TPD), known as dual or haplo-cord SCT, has shown to reduce the period of post-transplant neutropenia and related early morbidity and mortality associated with single CB transplantation. [5][6][7][8] This strategy offers a rapid neutrophil recovery at the expense firstly of TPD cells with subsequent replacement and long-term engraftment of CB cells.Graft failure and graft rejection are major complications after allogeneic SCT, with a frequency as high as 23% using CB transplants. 9-11 Outcome of patients who develop graft failure without a second transplantation is dismal with survival rates lower than 10%; 12 however, survival rates improve significantly to 30-60% after salvage transplantation using reduced intensity conditioning regimens. [13][14][15] From the extensive experience with CB transplantation, various risk factors have been associated with CB graft failure. [16][17][18] Once transplantation has been performed, early detection of graft failure is important to start rapid therapeutic measures such as immunomodulation and to launch a second transplan...

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Section: Standard Engraftment Group (N ¼ 14)mentioning

confidence: 99%

mentioning

confidence: 99%

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

Kwon

Martínez-Laperche

Balsalobre

et al. 2013

Bone Marrow Transplant

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“…Pre-existing donor-specific HLA antibodies in patients have been increasingly recognized as a risk factor for primary graft failure after HLA-mismatched SCT, 1 including unrelated SCT, 2,3 cord blood transplantation 4,5 or HLA-haploidentical SCT from family donors (haplo-SCT). 6,7 However, the clinical implications of the presence of HLA antibodies in donors remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

Taniguchi

Yoshihara

Maruya³

et al. 2012

Bone Marrow Transplant

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“…17,18 Positive serum crossmatch is predictive for graft failure in HLA-mismatched allogeneic SCT. 19,20 Thus, the fate of transplanted donor HSCs, namely engraftment or rejection is determined by the competition between donorderived and residual host-derived HSCs (stem cell competition) and by the competition between donor-derived and host-derived immune competent cells, such as T cells, NK cells and B cells (immunological competition). [11][12][13] We herein investigated the process of host T cell-mediated immunological graft rejection in a mouse model of RIC-SCT using sublethal irradiation conditioning 21 and in patients who underwent cord blood transplantation (CBT) following RIC (RIC-CBT) that represents a higher risk for graft rejection than other types of allogeneic SCT.…”

Section: Introductionmentioning

confidence: 99%

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning

Koyama

Hashimoto

Nagafuji

et al. 2013

Bone Marrow Transplant

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Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

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The impact of anti-HLA antibodies on unrelated cord blood transplantations

Cited by 222 publications

References 33 publications

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning

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