Haematological Sciences, Institute of Cellular Medicine, William Leech Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Haematologica. 2012 Jul;97(7):1014-9. doi: 10.3324/haematol.2011.053611. Epub 2012 Jan 22.
Allogeneic hematopoietic cell transplantation is the main curative therapy for patients with chronic myeloid leukemia who do not respond to tyrosine kinase inhibitors. It has been proposed that non-human leukocyte antigen gene polymorphisms influence outcome after hematopoietic cell transplantation and could be used alongside traditional patient-donor and transplant characteristics to create a recipient risk profile associated with allogeneic hematopoietic cell transplantation.
A previous study from the European Group for Blood and Marrow Transplantation showed that the absence of recipient tumor necrosis factor receptor II, absence of donor interleukin 10 ATA/ACC and presence of donor interleukin 1 receptor antagonist allele 2 genotypes were associated with decreased survival and increased non-relapse mortality in adult patients with chronic myeloid leukemia undergoing myeloablative human leukocyte antigen-identical sibling transplantation. To explore these associations in unrelated donor transplantation, these polymorphisms were genotyped in 383 adult patients with chronic myeloid leukemia who underwent hematopoietic cell transplantation from unrelated donors matched for 10/10 human leukocyte antigens.
The polymorphisms were not associated with overall survival, non-relapse mortality, relapse or acute graft-versus-host disease in the unrelated donor cohort. Comparison of the unrelated donor and human leukocyte antigen-identical sibling cohorts showed differences in survival and clinical characteristics.
We did not confirm that non-human leukocyte antigen polymorphisms were associated with outcomes in myeloablative unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia, possibly because of the strong association between clinical variables and outcome which masked more subtle genetic effects.
异基因造血细胞移植是对酪氨酸激酶抑制剂治疗无反应的慢性髓性白血病患者的主要治疗方法。有人提出，非人类白细胞抗原基因多态性影响造血细胞移植后的结果，并且可以与传统的患者-供体和移植特征一起，创建与异基因造血细胞移植相关的受体风险概况。
欧洲血液和骨髓移植组的一项先前研究表明，受体肿瘤坏死因子受体 II 缺失、供体白细胞介素 10ATA/ACC 缺失和供体白细胞介素 1 受体拮抗剂等位基因 2 基因型存在与成年慢性髓性白血病患者接受同种异体 HLA 匹配的同胞造血细胞移植后存活率降低和非复发死亡率增加相关。为了在无关供体移植中探索这些关联，在 383 名接受无关供体造血细胞移植的慢性髓性白血病成年患者中对这些多态性进行了基因分型，这些患者与 10/10 人类白细胞抗原相匹配。
在无关供体队列中，这些多态性与总生存率、非复发死亡率、复发或急性移植物抗宿主病无关。无关供体和 HLA 相同的同胞队列之间的比较显示生存和临床特征存在差异。
我们没有证实非人类白细胞抗原多态性与慢性髓性白血病的清髓性无关供体造血细胞移植的结果相关，可能是因为临床变量与结果之间的强烈关联掩盖了更微妙的遗传效应。
