Nikoloudis Alexander, Bauhofer Anna, Griessl Lena, Habermehl Anke, Groiss Christina, Binder Michaela, Milanov Robert, Bauer Thomas, Buxhofer-Ausch Veronika, Aichinger Christoph, Hasengruber Petra, Kaynak Emine, Wipplinger Dagmar, Strassl Irene, Stiefel Olga, Petzer Andreas, Rumpold Holger, Machherndl-Spandl Sigrid, Weltermann Ansgar, Clausen Johannes
Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz-Elisabethinen, Linz, Austria; Medical Faculty, Johannes Kepler University, Linz, Austria.
Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz-Elisabethinen, Linz, Austria; Medical Faculty, Johannes Kepler University, Linz, Austria.
Cytotherapy. 2025 Apr;27(4):457-464. doi: 10.1016/j.jcyt.2024.12.003. Epub 2024 Dec 24.
In HLA-identical hematopoietic stem cell transplantation (HSCT), HLA-C1 group killer cell immunoglobulin-like receptor (KIR) ligands have been linked to graft-versus-host disease, whereas C2 homozygosity was associated with increased relapses. The differential impact of the recipients versus the donor's HLA-C KIR ligands cannot be determined in HLA-identical HSCT but may be elucidated in the haploidentical setting, in which HLA-C (including the HLA-C KIR ligand group) mismatching is frequently present.
We retrospectively investigated the effect of recipient versus donor C1 ligand content on survival and complications in post-transplant cyclophosphamide (PTCy)-based haploidentical HSCT (n = 170). HSCTs were categorized as donor C1 supremacy (n = 34), C1 balance (n = 98), or donor C1 inferiority (n = 38).
Following HSCT from C1-inferior donors, overall mortality (hazard ratio, 2.84; P = 0.002) and non-relapse mortality (sub-hazard ratio [SHR], 3.86; P = 0.007) were significantly increased. Following HSCT from C1-superior donors, a low 1-year relapse incidence and favorable 1-year progression-free survival were observed. C1 supremacy did not significantly impact acute or chronic graft-versus-host disease, natural killer cell reconstitution, or day 21 chimerism. Infection was a more common cause of death among recipients with a C1-inferior donor compared with C1-superior or C1-balanced donors.
These findings suggest an increased risk for NRM, particularly infection-related deaths, associated with C1-inferior donors. Upon independent confirmation, C1-inferior donors should be avoided in PTCy-based haploidentical HSCT.
在人类白细胞抗原（HLA）全相合造血干细胞移植（HSCT）中，HLA - C1组杀伤细胞免疫球蛋白样受体（KIR）配体与移植物抗宿主病相关，而C2纯合性与复发增加有关。在HLA全相合HSCT中无法确定受者与供者HLA - C KIR配体的不同影响，但在半相合移植中可能得以阐明，因为半相合移植中常存在HLA - C（包括HLA - C KIR配体组）不匹配的情况。
我们回顾性研究了在基于移植后环磷酰胺（PTCy）的半相合HSCT（n = 170）中，受者与供者C1配体含量对生存和并发症的影响。HSCT被分类为供者C1优势型（n = 34）、C1平衡型（n = 98）或供者C1劣势型（n = 38）。
在接受C1劣势供者的HSCT后，总死亡率（风险比，2.84；P = 0.002）和非复发死亡率（亚风险比[SHR]，3.86；P = 0.007）显著增加。在接受C1优势供者的HSCT后，观察到1年复发率低且1年无进展生存率良好。C1优势对急性或慢性移植物抗宿主病、自然杀伤细胞重建或第21天嵌合率无显著影响。与C1优势或C1平衡供者相比，感染是接受C1劣势供者的受者中更常见的死亡原因。
这些发现表明与C1劣势供者相关的非复发死亡率增加风险，尤其是感染相关死亡。经独立证实后，在基于PTCy的半相合HSCT中应避免使用C1劣势供者。
