Woodard P, Wang W, Pitts N, Benaim E, Horwitz E, Cunningham J, Bowman L
Division of Bone Marrow Transplantation, Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Bone Marrow Transplant. 2001 Mar;27(6):589-92. doi: 10.1038/sj.bmt.1702827.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic anemia. Successful results may be obtained after conditioning and transplantation from syngeneic or genotypically matched sibling donors. Experience with transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent successful MUD BMT for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.
阵发性睡眠性血红蛋白尿（PNH）是一种由于PIG-A基因突变导致的后天性造血克隆性疾病。受影响的患者可能表现出溶血或静脉血栓形成，并可能发展为骨髓增生异常综合征（MDS）或再生障碍性贫血。在进行预处理并接受同基因或基因匹配的同胞供体移植后，可能会取得成功的结果。来自匹配无关供体（MUD）的移植经验仅限于8例患者，仅有1例存活。我们报告了3例接受MUD异基因造血干细胞移植（BMT）治疗PNH并获得成功的患者。所有3例患者在BMT时均患有严重再生障碍性贫血（SAA）和PNH。无关供体为6抗原HLA匹配（n = 2）或HLA-A不匹配（n = 1）。预处理方案包括阿糖胞苷、环磷酰胺、全身照射（TBI）和抗胸腺细胞球蛋白（ATG）。通过抗CD6/CD8抗体+补体去除移植物中的T细胞。进一步的移植物抗宿主病（GVHD）预防措施包括环孢素。患者接受了0.7 - 1.1×10⁸有核细胞/kg和1.1 - 2.1×10⁶ CD34⁺细胞/kg的移植。中性粒细胞在16 - 21天植入。1例患者发生了1级急性GVHD。尽管所有3例患者都经历了严重的移植相关并发症，但最终均得到解决，所有患者在BMT后30 - 62个月均存活且状况良好。去除T细胞的MUD BMT是治疗与PNH相关的MDS和SAA的有效治疗选择。
