Casper J T, Truitt R R, Baxter-Lowe L A, Ash R C
Midwest Children's Cancer Center, MACC Fund Research Center, Milwaukee, WI 53226.
Am J Pediatr Hematol Oncol. 1990 Winter;12(4):434-48. doi: 10.1097/00043426-199024000-00007.
For young adults and children who have a bone marrow donor who is a genotypic or phenotypic sibling match, bone marrow transplantation is now the preferred treatment for severe aplastic anemia. For those who lack such a matched donor, use of matched unrelated donors and family member donors who are mismatched for a single HLA antigen have been successful and appear to be the treatment of choice. Patients lacking either of these alternatives should receive antilymphocyte globulin, either alone or combined with cyclosporine as a first step. Although the success rate of marrow transplants in our series using mismatched family donors is similar to that following treatment with antilymphocyte globulin, several caveats must be kept in mind. First, the results reported with use of alternative donors must be confirmed with study of larger numbers of patients and longer follow-up. Second, the preparative regimen given prior to bone marrow transplantation destroys the patient's residual bone marrow, whereas antilymphocyte globulin cyclosporine A and androgens do not. The sequence of immunosuppression followed by transplantation with alternative donor marrow should produce greater long-term hematopoietic improvement. Unfortunately, when marrow transplant follows one or more courses of immunosuppressive therapy, nonengraftment is then a problem because of sensitization to blood cell antigens. It should also be kept in mind that studies done in children, especially in those younger than 6 years old, show that these patients respond better to transplantation than to treatment regimens not including marrow transplantation. Therefore, for the child with severe aplastic anemia, every effort should be made to identify a suitable bone marrow donor. Finally, we need to determine the specific components of the conditioning regimen and the constitution of the donor marrow necessary for engraftment and to minimize potential long-term complications, and there should be only a tolerable degree of graft-versus-host disease. Many of the transplant-related problems that plagued us in the 1970s have still not been fully resolved, but many have shown improvement. As we enter the 1990s, increasing the pool of marrow donors for patients with severe aplastic anemia who lack an HLA-matched sibling will continue to be a top priority for research.
对于有基因型或表型匹配的同胞骨髓供者的年轻成人和儿童，骨髓移植目前是重型再生障碍性贫血的首选治疗方法。对于那些缺乏这种匹配供者的患者，使用匹配的无关供者以及单个HLA抗原不匹配的家庭成员供者已取得成功，似乎是首选的治疗方法。缺乏这两种替代方案的患者应首先接受抗淋巴细胞球蛋白治疗，可单独使用或与环孢素联合使用。尽管在我们使用不匹配的家庭供者进行的系列骨髓移植中成功率与抗淋巴细胞球蛋白治疗后的成功率相似，但必须牢记几个注意事项。首先，使用替代供者报告的结果必须通过对更多患者的研究和更长时间的随访来证实。其次，骨髓移植前给予的预处理方案会破坏患者残留的骨髓，而抗淋巴细胞球蛋白、环孢素A和雄激素则不会。免疫抑制后再用替代供者骨髓进行移植的顺序应能带来更大的长期造血改善。不幸的是，当骨髓移植在一个或多个免疫抑制疗程之后进行时，由于对血细胞抗原致敏，植入失败就会成为一个问题。还应牢记，在儿童中进行的研究，尤其是6岁以下的儿童，表明这些患者对移植的反应比对不包括骨髓移植的治疗方案更好。因此，对于患有重型再生障碍性贫血的儿童，应尽一切努力确定合适的骨髓供者。最后，我们需要确定预处理方案的具体组成部分以及植入所需的供者骨髓的构成，并尽量减少潜在的长期并发症，且移植物抗宿主病的程度应在可耐受范围内。许多在20世纪70年代困扰我们的与移植相关的问题仍未完全解决，但许多问题已有所改善。随着我们进入20世纪90年代，为缺乏HLA匹配同胞的重型再生障碍性贫血患者增加骨髓供者库将仍然是研究的首要任务。
