造血祖细胞移植后镰状细胞病患者的免疫血液学并发症：一项前瞻性、单中心观察性研究
Immunohaematological complications in patients with sickle cell disease after haemopoietic progenitor cell transplantation: a prospective, single-centre, observational study.
作者信息
Allen Elizabeth S, Srivastava Kshitij, Hsieh Matthew M, Fitzhugh Courtney D, Klein Harvey G, Tisdale John F, Flegel Willy A
机构信息
Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
出版信息
Lancet Haematol. 2017 Nov;4(11):e553-e561. doi: 10.1016/S2352-3026(17)30196-5.
BACKGROUND
Haemopoietic progenitor cell (HPC) transplantation can cure sickle cell disease. Non-myeloablative conditioning typically results in donor-derived erythrocytes and stable mixed chimerism of recipient-derived and donor-derived leucocytes. Exposure to donor antigens from the HPC graft and new red cell antibodies induced by transfusion can lead to immunohaematological complications. We assessed the incidence of such complications among HPC transplant recipients with sickle cell disease.
METHODS
The study population was all patients with sickle cell disease enrolled before March 31, 2015, in the three clinical trials of non-myeloablative HPC transplantation at the National Institutes of Health. We assessed formation of new red cell antibodies after transplantation and red cell incompatibility between donors and recipients.
FINDINGS
61 patients were enrolled, 42 were HLA matched and 19 were haploidentical. Nine (15%) had immunohaematological complications. Before HPC transplantation, three patients had antibodies incompatible with their donors. After HPC transplantation, new red cell antibodies were seen in six patients (11 alloantibodies and two autoantibodies), among whom three developed antibodies incompatible with donor or recipient red cells and three developed compatible antibodies. The clinical course of complications was highly variable, from no severe effects attributable to antibodies, to sustained reticulocytopenia, to near-fatal haemolysis. We found no significant correlation between immunohaematological complications and graft failure, graft rejection, or death.
INTERPRETATION
Clinical effects ranged from seemingly not clinically important to potentially fatal. In patients with sickle cell disease, donor and recipient red cell phenotypes should be carefully assessed before transplantation to minimise and manage the risk of immunohaematological complications.
FUNDING
Intramural Research Program and National Institutes of Health.
背景
造血祖细胞（HPC）移植可治愈镰状细胞病。非清髓性预处理通常会产生供体来源的红细胞以及受体来源和供体来源白细胞的稳定混合嵌合体。接触HPC移植物中的供体抗原以及输血诱导产生的新红细胞抗体会导致免疫血液学并发症。我们评估了镰状细胞病HPC移植受者中此类并发症的发生率。
方法
研究人群为2015年3月31日前在美国国立卫生研究院进行的三项非清髓性HPC移植临床试验中登记的所有镰状细胞病患者。我们评估了移植后新红细胞抗体的形成以及供体和受体之间的红细胞不相容性。
结果
登记了61例患者，其中42例HLA匹配，19例单倍型相同。9例（15%）发生免疫血液学并发症。在HPC移植前，3例患者有与供体不相容的抗体。HPC移植后，6例患者出现新的红细胞抗体（11种同种抗体和2种自身抗体），其中3例产生了与供体或受体红细胞不相容的抗体，3例产生了相容抗体。并发症的临床过程差异很大，从无抗体引起的严重影响到持续性网织红细胞减少，再到近乎致命的溶血。我们发现免疫血液学并发症与移植物失败、移植物排斥或死亡之间无显著相关性。
解读
临床影响范围从看似无临床重要性到潜在致命性。对于镰状细胞病患者，移植前应仔细评估供体和受体的红细胞表型，以最小化并管理免疫血液学并发症的风险。
资助
内部研究项目和美国国立卫生研究院。
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