Adult HSCT Program, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Biol Blood Marrow Transplant. 2011 May;17(5):717-22. doi: 10.1016/j.bbmt.2010.08.013. Epub 2010 Aug 22.
Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m(2)/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 10(8)/kg (range, 0.60-6.7 × 10(8)/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.
38 名符合重型再生障碍性贫血诊断标准的患者接受了异基因造血干细胞移植（HSCT）。中位患者年龄为 20 岁（范围 14-36 岁）。24 例患者为初治患者，11 例患者在前一次或多次免疫抑制治疗中失败，3 例患者在前一次 HSCT 中失败。预处理方案包括 3 天（-9、-8 和-7 天）每天 30mg/m2 的氟达拉滨和 4 天（-5、-4、-3 和-2 天）每天 50mg/kg 的环磷酰胺。移植物抗宿主病（GVHD）预防包括环孢素和短程甲氨蝶呤。所有患者均接受未经处理的骨髓作为干细胞来源进行移植。中位总核细胞（TNC）剂量为 2.43×108/kg（范围 0.60-6.7×108/kg）。预处理方案耐受性良好，治疗相关死亡率低。移植后所有患者均观察到植入；中性粒细胞和血小板植入的中位时间分别为 18 天和 23 天。在 27 例有可用嵌合研究的患者中，有 25 例在 180 天维持供者嵌合。4 例（11%）诊断为≥Ⅱ级急性 GVHD。8 例（25%）患者在+100 天以上存活时观察到广泛的慢性 GVHD，中位观察时间为 43 个月。1 例患者观察到移植物排斥伴再生障碍性贫血复发。整个组别的总生存率（OS）为 79%。初治患者的 OS 有改善趋势（83%比 71%），但无统计学意义（P=0.384）。该研究中使用的氟达拉滨为基础的预处理方案与相对年轻的患者群体具有良好的耐受性，排斥率低，治疗结果与其他更强烈且潜在毒性更大的预处理方案相当。我们的结果有待更大规模的研究进一步验证，最佳方式是随机对照研究。
