Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation

Yao MA; Yanfang ZHANG; Kang ZHOU; Yun LUO; Shu CHEN; Shifeng LOU; Jianchuan DENG

doi:10.16016/j.2097-0927.202309072

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Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation

Monographic Reports: Advances in diagnosis and treatment for hematological malignancies | 更新时间：2026-01-09

- Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation
- Journal of Army Medical University Vol. 46, Issue 4, Pages: 319-325(2024)
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院血液内科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202309072
  CLC： R392.4;R617;R733.7
- Received：13 September 2023，
  
  Revised：2023-12-22，
  
  Published：28 February 2024
- 稿件说明：
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Yao MA, Yanfang ZHANG, Kang ZHOU, et al. Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation[J]. Journal of Army Medical University, 2024, 46(4): 319-325.
DOI：

Yao MA, Yanfang ZHANG, Kang ZHOU, et al. Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation[J]. Journal of Army Medical University, 2024, 46(4): 319-325. DOI： 10.16016/j.2097-0927.202309072.

摘要

目的

分析供者特异性HLA抗体(anti-HLA donor-specific antibodies

DSA)及DSA阳性患者的去敏治疗对单倍体造血干细胞移植(haploidentical hematopoietic stem cell transplantation

haplo-HSCT)植入效果的影响。

方法

收集2017年3月至2023年7月重庆医科大学附属第二医院血液内科行haplo-HSCT

并完成HLA抗体及DSA检测的患者70例

分析DSA阳性和DSA阳性患者去敏治疗对造血干细胞移植植入效果的影响。

结果

70例haplo-HSCT患者完成抗体检测

DSA阳性患者15例(21.4%)

其中7例(46.7%)强阳性

3例(20.0%)中度阳性

5例(33.3%)弱阳性。DSA阳性患者移植后粒系植入中位时间较DSA阴性患者明显延迟(

=0.027)。植入失败(graft failure

GF)患者6例

DSA阳性4例(26.7%)

明显高于DSA阴性(

=0.025)。多因素分析结果显示

DSA是发生GF的独立影响因素(

=9.273

95%

=1.505~57.124

=0.016)。10例DSA中度和强阳性患者进行去敏治疗

4例采用联合去敏治疗

患者均成功植入(100.0%)

6例采用单一去敏治疗

有4例(66.7%)发生GF

联合去敏治疗的GF发生率显著低于单一去敏治疗(

=0.008)。

结论

DSA是导致haplo-HSCT患者植入延迟和GF的重要因素

对DSA中度及强阳性患者的单一去敏治疗效果有限

而多联合的去敏治疗时

动态监测抗体滴度水平下降

可保证干细胞的成功植入

降低GF发生。

Abstract

Objective

To investigate the effects of anti-HLA donor-specific antibodies (DSA) and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

Methods

The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.

Results

Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies

15(21.4%) patients were DSA positive

including 7(46.7%) cases of strong positive

3(20.0%) cases of moderate positive

and 5(33.3%) cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients (

=0.027).For the 6 patients developed graft failure (GF)

4 were DSA+which was statistically higher than the DSA-patients (

=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF (

=9.273

95%

: 1.505~57.124

=0.016).Among the 10 patients (7 strong positive and 3 moderate positive DSA) received desensitization therapy

4 patients received combination desensitization

with a 100% rate of successful transplantation

and 6 received single desensitization

with 4(66.7%) experiencing GF

so the GF rate was obviously lower in the combination than the single desensitization (

=0.008).

Conclusion

In haplo-HSCT patients

DSA is an important factor leading to implantation delay and GF.While

single desensitization treatment has limited efficacy.In combined DSA desensitization therapy

the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

关键词

Keywords

references

SNOWDEN J A, SÁNCHEZ-ORTEGA I, CORBACIOGLU S, et al . Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022[J ] . Bone Marrow Transplant, 2022, 57(8): 1217-1239. DOI: 10.1038/s41409-022-01691-w.

TIMOFEEVA O A, PHILOGENE M C, ZHANG Q J. Current donor selection strategies for allogeneic hematopoietic cell transplantation[J]. Hum Immunol, 2022, 83(10): 674-686. DOI: 10.1016/j.humimm.2022.08.007.

AULETTA J J, KOU J Q, CHEN M, et al . Real-world data showing trends and outcomes by race and ethnicity in allogeneic hematopoietic cell transplantation: a report from the center for international blood and marrow transplant research[J ] . Transplant Cell Ther, 2023, 29(6): 346. e1-346. e10. DOI: 10.1016/j.jtct.2023.03.007.

CIUREA S O, THALL P F, WANG X M, et al . Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation[J ] . Blood, 2011, 118(22): 5957-5964. DOI: 10.1182/blood-2011-06-362111.

CIUREA S O, THALL P F, MILTON D R, et al . Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation[J ] . Biol Blood Marrow Transplant, 2015, 21(8): 1392-1398. DOI: 10.1016/j.bbmt.2015.05.001.

AKHTAR W, PETERZAN M A, BANYA W, et al . Donor specific antibodies association with survival and adverse events after heart transplantation: a single center retrospective study between 2006 and 2021[J ] . Clin Transplant, 2023, 37(4): e14914. DOI: 10.1111/ctr.14914.

ROCCA U L, PERRONE M P, PICIOCCHI A, et al . Anti-HLA donor-specific antibodies in allogeneic stem cell transplantation: management and desensitization protocol[J ] . Bone Marrow Transplant, 2019, 54(10): 1717-1720. DOI: 10.1038/s41409-019-0497-1.

LIMA A C M, GETZ J, DO AMARAL G B, et al . Donor-specific HLA antibodies are associated with graft failure and delayed hematologic recovery after unrelated donor hematopoietic cell transplantation[J ] . Transplant Cell Ther, 2023, 29(8): 493. e1-493. e10. DOI: 10.1016/j.jtct.2023.05.014.

HUANG Y R, LUO C X, WU G X, et al . Effects of donor-specific antibodies on engraftment and long-term s urvival after allogeneic hematopoietic stem cell transplantation-a systematic review and meta-analysis[J ] . Bone Marrow Transplant, 2023, 58(5): 544-551. DOI: 10.1038/s41409-023-01932-6.

APPERLEY J, NIEDERWIESER D, HUANG X J, et al . Haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European union, and the United States[J ] . Biol Blood Marrow Transplant, 2016, 22(1): 23-26. DOI: 10.1016/j.bbmt.2015.11.001.

CIUREA S O, CAO K, FERNANDEZ-VINA M, et al . The European society for blood and marrow transplantation (EBMT) consensus guidelines for the detection and treatment of donor-specific anti-HLA antibodies (DSA) in haploidentical hematopoietic cell transplantation[J ] . Bone Marrow Transplant, 2018, 53(5): 521-534. DOI: 10.1038/s41409-017-0062-8.

ALTAREB M, AL-AWWAMI M, ALFRAIH F, et al . Incidence and significance of donor-specific antibodies in haploidentical stem cell transplantation[J ] . Bone Marrow Transplant, 2023, 58(6): 680-686. DOI: 10.1038/s41409-023-01950-4.

JO T, ARAI Y, HATANAKA K, et al . Adverse effect of donor-specific anti-human leukocyte antigen (HLA) antibodies directed at HLA-DP /-DQ on engraftment in cord blood transplantation[J ] . Cytotherapy, 2023, 25(4): 407-414. DOI: 10.101 6/j.jcyt.2022.10.005.

KRUMMEY S M, GAREAU A J. Donor specific HLA antibody in hematopoietic stem cell transplantation: implications for donor selection[J]. Front Immunol, 2022, 13: 916200. DOI: 10.3389/fimmu.2022.916200.

ZOU J, ROMEE R, SLADE M, et al . Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation[J ] . Bone Marrow Transplant, 2017, 52(6): 898-901. DOI: 10.1038/bmt.2017.7.

LA ROCCA U, PERRONE M P, PICIOCCHI A, et al . Donor specific anti-HLA antibodies in hematopoietic stem cell transplantation. Single center prospective evaluation and desensitization strategies employed[J ] . Blood Transfus, 2023. [Epub ahead of print ] . DOI: 10.2450/BloodTransfus.464.

BAILÉN R, ALENDA R, HERRUZO-DELGADO B, et al . Results of haploidentical transplant in patients with donor-specific antibodies: a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy[J ] . Front Immunol, 2023, 14: 1165759. DOI: 10.3389/fimmu.2023.1165759.

MISRA M K, XIN J J, BROWN N K, et al . Effective desensitization for a strong donor-specific HLA antibody in a case of HLA-mismatched allogeneic hematopoietic cell transplantation[J ] . HLA, 2019, 94(3): 307-311. DOI: 10.1111/tan.13627.

王志东, 孙于谦, 闫晨华, 等. 单倍型相合造血干细胞移植前血液病患者体内供者特异性抗人类白细胞抗原抗体水平对利妥昔单抗去敏治疗后造血重建不良的影响分析[J]. 中华内科杂志, 2021, 60(7): 644-649. DOI: 10.3760/cma.j.cn112138-20200728-00713.

WANG Z D, SUN Y Q, YAN C H, et al . Negative effects of donor specific anti-HLA antibody on poor hematopoietic recovery in patients with hematological diseases receiving haploidentical stem cell transplantation and rituximab for desensitization[J ] . Chin J Intern Med, 2021, 60(7): 644-649. DOI: 10.3760/cma.j.cn112138-20200728-00713.

CHOE H, GERGIS U, HSU J, et al . Bortezomib and immune globulin have limited effects on donor-specific HLA antibodies in haploidentical cord blood stem cell transplantation: detrimental effect of persistent haploidentical donor-specific HLA antibodies[J ] . Biol Blood Marrow Transplant, 2019, 25(2): e60-e64. DOI: 10.1016/j.bbmt.2018.10.018.

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