Donor-Specific HLA Antibodies Are Associated with Graft Failure and Delayed Hematologic Recovery after Unrelated Donor Hematopoietic Cell Transplantation

被引:9
|
作者
Martins Lima, Alberto Cardoso [1 ,2 ]
Getz, Joselito [1 ]
do Amaral, Geovana Borsato [1 ]
Loth, Gisele [3 ,4 ]
Moreira Funke, Vaneuza Araujo [3 ]
Nabhan, Samir Kanaan [3 ]
Petterle, Ricardo Rasmussen [5 ]
de Marco, Renato [2 ]
Gerbase-DeLima, Maria [2 ]
Pereira, Noemi Farah [1 ]
Bon, Carmem [3 ,4 ]
Pasquini, Ricardo [3 ]
机构
[1] Univ Fed Parana, Complexo Hosp Clin, Histocompatibil Lab, Rua Padre Camargo,280 1o Andar, BR-80060240 Curitiba, PR, Brazil
[2] Assoc Fundo Incent Pesquisa AFIP, Immunogenet Inst Igen, Sao Paulo, SP, Brazil
[3] Univ Fed Parana, Complexo Hosp Clin, Bone Marrow Transplantat Unit, Curitiba, PR, Brazil
[4] Hosp Pequeno Principe, Inst Pesquisa Pele Pequeno Principe, Curitiba, PR, Brazil
[5] Univ Fed Parana, Dept Integrat Med, Curitiba, PR, Brazil
来源
TRANSPLANTATION AND CELLULAR THERAPY | 2023年 / 29卷 / 08期
关键词
Donor-specific anti-HLA; antibodies; Unrelated donor transplantation; Graft failure; Delayed hematologic recovery; ALLOANTIBODIES; REJECTION; STRENGTH;
D O I
10.1016/j.jtct.2023.05.014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Graft failure (GF) is one of the major concerns after allogeneic hematopoietic cell transplantation (allo-HCT) and remains a significant cause of morbidity and mortality. Although previous reports have associated the presence of donor-specific HLA antibodies (DSAs) with an increased risk of GF after unrelated donor allo-HCT, recent studies have failed to confirm this association. We sought to validate the presence of DSAs as a risk factor for GF and hematologic recovery in the unrelated donor allo-HCT setting. We retrospectively evaluated 303 consecutive patients who under-went their first unrelated donor allo-HCT at our institution between January 2008 and December 2017. DSA evaluation was performed using 2 single antigen bead (SAB) assays; DSA titration with 1:2, 1:8, and 1:32 dilutions; C1q-binding assay; and absorption/elution protocol to assess possible false-positive DSA reactivity. The primary endpoints were neutrophil and platelet recovery and GF, and the secondary endpoint was overall survival. Multivariable analyses were performed using Fine-Gray competing risks regression and Cox proportional hazards regression models. The median patient age was 14 years (range, 0 to 61 years), 56.1% were male, and 52.5% underwent allo-HCT for nonmalig-nant disease, Eleven patients (3.63%) were DSA-positive, including 10 with preexisting DSAs and 1 with post-trans-plantation de novo DSAs. Nine patients had 1 DSA, 1 patient had 2 DSAs, and 1 patient had 3 DSAs, with a median mean fluorescent intensity (MFI) of 4334 (range, 588 to 20,456) and 3581 (range, 227 to 12,266) in LABScreen and LIFECODES SAB assays, respectively. Overall, 21 patients experienced GF, including 12 with primary graft rejection, 8 with secondary graft rejection, and 1 with primary poor graft function. The cumulative incidence of GF was 4.0% (95% confidence interval [CI], 2.2% to 6.6%) at 28 days, 6.6% (95% CI, 4.2% to 9.8%) at 100 days, and 6.9% (95% CI, 4.4% to 10.2%) at 365 days. In the multivariable analyses, DSA-positive patients had significantly delayed neutrophil recovery (subdistribution hazard ratio [SHR], .48; 95% CI, .29 to .81; P = .006) and platelet recovery (SHR, .51; 95% CI, .35 to .74; P = .0003) compared to patients without DSAs. In addition, only DSAs were significant predictors of primary GF at 28 days (SHR, 2.78; 95% CI, 1.65 to 4.68; P = .0001). The Fine-Gray regression also demonstrated that the presence of DSAs was strongly associated with a higher incidence of overall GF (SHR, 7.60; 95% CI, 2.61 to 22.14; P = .0002). DSA-positive patients with GF had significantly higher median MFI values than DSA-positive patients who achieved engraft-ment in the LIFECODES SAB assay using neat serum (10,334 versus 1250; P = .006) and in the LABScreen SAB at 1:32 dilution (1627 versus 61; P = .006). All 3 patients with C1q-positive DSAs failed to engraft. DSAs were not predictive of inferior survival (HR, .50; 95% CI, .20 to 1.26; P = .14). Our results validate the presence of DSAs as a significant risk factor for GF and delayed hematologic recovery after unrelated donor allo-HCT. Careful pretransplantation DSA evalua-tion may optimize unrelated donor selection and improve allo-HCT outcomes.& COPY; 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:493.e1 / 493.e10
页数:10
相关论文
共 50 条
  • [21] DONOR-SPECIFIC ANTI-HLA ANTIBODIES IN HLA-MISMATCHED HEMATOPOIETIC STEM CELL TRANSPLANTATION
    Focosi, Daniele
    TISSUE ANTIGENS, 2012, 79 (06): : 445 - 445
  • [22] Second Unrelated Donor Hematopoietic Cell Transplantation for Primary Graft Failure
    Schriber, Jeffrey
    Agovi, Manza-A
    Ho, Vincent
    Ballen, Karen K.
    Bacigalupo, Andrea
    Lazarus, Hillard M.
    Bredeson, Christopher N.
    Gupta, Vikas
    Maziarz, Richard T.
    Hale, Gregory A.
    Litzow, Mark R.
    Logan, Brent
    Bornhauser, Martin
    Giller, Roger H.
    Isola, Luis
    Marks, David I.
    Rizzo, J. Douglas
    Pasquini, Marcelo C.
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2010, 16 (08) : 1099 - 1106
  • [23] Development of donor specific HLA antibodies is associated with graft failure
    Rebellato, Lorita M.
    Ozawa, Miyuki
    Briley, Kimberly P.
    Catrou, Paul
    Haisch, Carl E.
    Terasaki, Paul I.
    HUMAN IMMUNOLOGY, 2007, 68 : S44 - S44
  • [24] THE ROLE OF DONOR-SPECIFIC ANTI-HLA ANTIBODIES (DSA) IN HEMATOPOIETIC STEM CELL TRANSPLANTATION FROM MATCHED UNRELATED DONORS
    Ciurea, S. O.
    Cano, P.
    de Lima, M.
    Thall, P. F.
    Rondon, G.
    Kebriaei, P.
    Alousi, A.
    Hosing, C.
    Khouri, I. F.
    Champlin, R. E.
    Fernandez-Vina, M.
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2010, 16 (02) : S158 - S158
  • [25] Impact of Donor-Directed HLA Allo-Antibodies on Primary Graft Failure After Unrelated Donor Allogeneic Haematopoietic Cell Transplantation
    Cuadrado, Maria M.
    Anthias, Chloe
    Fernando, Raymond
    Szydlo, Richard M.
    Marsh, Steven G. E.
    Mayor, Neema P.
    Chakraverty, Ronjon
    Madrigal, J. Alejandro
    Latham, Katy
    BONE MARROW TRANSPLANTATION, 2020, 55 (SUPPL 1) : 133 - 134
  • [26] Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft
    Yunusov, Murad Y.
    Kuhr, Christian S.
    Georges, George E.
    Hogan, William J.
    Taranova, Anna G.
    Lesnikova, Marina
    Kim, Yang-Soo
    Abrams, Kraig
    Hwang, Billanna
    Sale, George E.
    Storer, Barry
    Storb, Rainer
    Nash, Richard A.
    TRANSPLANTATION, 2006, 82 (05) : 629 - 637
  • [27] Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption
    Kaelble, Florian
    Suesal, Caner
    da Silva, Luiza Pego
    Speer, Claudius
    Benning, Louise
    Nusshag, Christian
    Pham, Lien
    Tran, Hien
    Schaier, Matthias
    Sommerer, Claudia
    Beimler, Joerg
    Mehrabi, Arianeb
    Zeier, Martin
    Morath, Christian
    FRONTIERS IN MEDICINE, 2021, 8
  • [28] ANTI-HLA DONOR-SPECIFIC ANTIBODIES ARE ASSOCIATED TO INFECTION AND NOT TO THE ENGRAFTMENT RATE IN OUTPATIENT HAPLOIDENTICAL HEMATOPOIETIC CELL TRANSPLANTATION
    Jaime-Perez, Jose C.
    Ruiz-De La Cruz, Maria L.
    Mendoza-Ibarra, Sandra I.
    Moncada-Saucedo, Nidia K.
    Gomez-Almaguer, David
    REVISTA DE INVESTIGACION CLINICA-CLINICAL AND TRANSLATIONAL INVESTIGATION, 2023, 75 (05): : 249 - 258
  • [29] LIVING DONOR KIDNEY TRANSPLANTATION IN PATIENTS WITH DONOR-SPECIFIC HLA ANTIBODIES AFTER DESENSITIZATION WITH IMMUNOADSORPTION
    Kaelble, Florian
    Susal, Caner
    Da Silva, Luiza Pego
    Speer, Claudius
    Benning, Louise
    Nusshag, Christian
    Schaier, Matthias
    Sommerer, Claudia
    Beimler, Joerg
    Mehrabi, Arianeb
    Zeier, Martin
    Morath, Christian
    TRANSPLANT INTERNATIONAL, 2021, 34 : 182 - 183
  • [30] Donor-specific HLA antibodies and renal allograft failure
    Alexandre Loupy
    Stanley C. Jordan
    Nature Reviews Nephrology, 2013, 9 : 130 - 131