Buckley R H, Schiff S E, Schiff R I, Markert L, Williams L W, Roberts J L, Myers L A, Ward F E
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
N Engl J Med. 1999 Feb 18;340(7):508-16. doi: 10.1056/NEJM199902183400703.
Since 1968 it has been known that bone marrow transplantation can ameliorate severe combined immunodeficiency, but data on the long-term efficacy of this treatment are limited. We prospectively studied immunologic function in 89 consecutive infants with severe combined immunodeficiency who received hematopoietic stem-cell transplants at Duke University Medical Center between May 1982 and September 1998.
Serum immunoglobulin levels and lymphocyte phenotypes and function were assessed and genetic analyses performed according to standard methods. Bone marrow was depleted of T cells by agglutination with soybean lectin and by sheep-erythrocyte rosetting before transplantation.
Seventy-seven of the infants received T-cell-depleted, HLA-haploidentical parental marrow, and 12 received HLA-identical marrow from a related donor; 3 of the recipients of haploidentical marrow also received placental-blood transplants from unrelated donors. Except for two patients who received placental blood, none of the recipients received chemotherapy before transplantation or prophylaxis against graft-versus-host disease. Of the 89 infants, 72 (81 percent) were still alive 3 months to 16.5 years after transplantation, including all of the 12 who received HLA-identical marrow, 60 of the 77 (78 percent) who were given haploidentical marrow, and 2 of the 3 (67 percent) who received both haploidentical marrow and placental blood. T-cell function became normal within two weeks after transplantation in the patients who received unfractionated HLA-identical marrow but usually not until three to four months after transplantation in those who received T-cell-depleted marrow. At the time of the most recent evaluation, all but 4 of the 72 survivors had normal T-cell function, and all the T cells in their blood were of donor origin. B-cell function remained abnormal in many of the recipients of haploidentical marrow. In 26 children (5 recipients of HLA-identical marrow and 21 recipients of haploidentical marrow) between 2 percent and 100 percent of B cells were of donor origin. Forty-five of the 72 children were receiving intravenous immune globulin.
Transplantation of marrow from a related donor is a life-saving and life-sustaining treatment for patients with any type of severe combined immunodeficiency, even when there is no HLA-identical donor.
自1968年以来，已知骨髓移植可改善严重联合免疫缺陷，但关于这种治疗长期疗效的数据有限。我们对1982年5月至1998年9月期间在杜克大学医学中心接受造血干细胞移植的89例连续性严重联合免疫缺陷婴儿的免疫功能进行了前瞻性研究。
根据标准方法评估血清免疫球蛋白水平、淋巴细胞表型和功能，并进行基因分析。移植前通过大豆凝集素凝集和绵羊红细胞花环法去除骨髓中的T细胞。
77例婴儿接受了去除T细胞的、HLA单倍型相同的亲代骨髓，12例接受了来自相关供体的HLA相同骨髓；3例接受单倍型相同骨髓的受者还接受了来自无关供体的胎盘血移植。除2例接受胎盘血的患者外，所有受者在移植前均未接受化疗或预防移植物抗宿主病。89例婴儿中，72例（81%）在移植后3个月至16.5年仍存活，包括所有12例接受HLA相同骨髓的婴儿、77例接受单倍型相同骨髓的婴儿中的60例（78%）以及3例同时接受单倍型相同骨髓和胎盘血的婴儿中的2例（67%）。接受未分离的HLA相同骨髓的患者移植后两周内T细胞功能恢复正常，但接受去除T细胞骨髓的患者通常直到移植后三至四个月T细胞功能才恢复正常。在最近一次评估时，72例存活者中除4例T细胞功能正常外，其余所有患者血液中的T细胞均来自供体。许多接受单倍型相同骨髓的受者B细胞功能仍异常。26例儿童（5例接受HLA相同骨髓，21例接受单倍型相同骨髓）中，2%至100%的B细胞来自供体。72例儿童中有45例正在接受静脉注射免疫球蛋白治疗。
对于任何类型的严重联合免疫缺陷患者，即使没有HLA相同的供体，接受相关供体的骨髓移植也是一种挽救生命和维持生命的治疗方法。
