Loughran T P, Storb R
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Hematol Oncol Clin North Am. 1990 Jun;4(3):559-75.
Survival of patients with aplastic anemia after immunosuppressive therapy with ATG/ALG ranges from 35% to 60%. However, long-term follow-up on these patients has indicated a high frequency of hematologic complications, including PNH, myelodysplasia, ANL, and recurrent aplasia. In contrast to immunosuppressive therapy, allogeneic marrow transplantation results in cure of aplasia. Problems initially limiting the success of HLA-matched allogeneic marrow transplants included graft rejection and complications associated with acute and chronic GVHD. Infusion of donor buffy coat cells along with marrow or alternatively more intensive immunosuppressive regimens containing irradiation have substantially decreased the risk of rejection. However, buffy coat infusion increases the incidence of chronic GVHD and irradiation treatment adds to toxicity of the conditioning regimen as well as producing long-term complications. The incidence and severity of acute GVHD have been significantly decreased by the use of MTX/CSP as GVHD prophylaxis; however, this regimen has had no impact on the incidence of chronic GVHD. Long-term survival in multiply transfused patients after HLA-identical marrow transplantation is on the order of 60% to 70%; survival in untransfused patients approximates 80%. Patients less than age 18 transplanted on protocols currently active in Seattle have greater than 90% survival. Further increases in survival must come from improvement in preventing and treating chronic GVHD. Patients diagnosed with aplastic anemia should have rapid HLA typing performed to identify possible marrow donors. Transfusions from prospective marrow donors should be avoided and the patient referred to a major treatment center. We continue to recommend allogeneic marrow transplantation for patients with severe aplastic anemia who are less than 40 years old and who have HLA-identical related donors. Immunosuppressive therapy should be tried first in patients without HLA-matched donors and for patients over the age of 40. HLA-mismatched marrow transplantation and use of unrelated marrow donors for severe aplastic anemia remain areas of active research.
再生障碍性贫血患者接受抗胸腺细胞球蛋白/抗淋巴细胞球蛋白免疫抑制治疗后的生存率为35%至60%。然而，对这些患者的长期随访表明血液学并发症的发生率很高，包括阵发性睡眠性血红蛋白尿症、骨髓增生异常综合征、急性髓系白血病和再生障碍性贫血复发。与免疫抑制治疗相反，异基因骨髓移植可治愈再生障碍性贫血。最初限制HLA匹配的异基因骨髓移植成功的问题包括移植物排斥以及与急性和慢性移植物抗宿主病相关的并发症。输注供体白细胞层细胞以及骨髓，或者采用包含照射的更强效免疫抑制方案，已大幅降低了排斥风险。然而，输注白细胞层会增加慢性移植物抗宿主病的发生率，而照射治疗会增加预处理方案的毒性并产生长期并发症。使用甲氨蝶呤/环孢素作为移植物抗宿主病预防措施后，急性移植物抗宿主病的发生率和严重程度已显著降低；然而，该方案对慢性移植物抗宿主病的发生率没有影响。接受HLA相同骨髓移植的多次输血患者的长期生存率约为60%至70%；未输血患者的生存率约为80%。在西雅图目前正在开展的方案下接受移植的18岁以下患者的生存率超过90%。生存率的进一步提高必须来自预防和治疗慢性移植物抗宿主病方面的改善。诊断为再生障碍性贫血的患者应尽快进行HLA分型以确定可能的骨髓供体。应避免接受潜在骨髓供体的输血，并将患者转诊至主要治疗中心。对于年龄小于40岁且有HLA相同相关供体的重型再生障碍性贫血患者，我们继续推荐异基因骨髓移植。对于没有HLA匹配供体的患者以及40岁以上的患者，应首先尝试免疫抑制治疗。HLA不匹配的骨髓移植以及使用无关骨髓供体治疗重型再生障碍性贫血仍是活跃的研究领域。
