Department of Haematology, Christian Medical College, Ida Scudder Road, Vellore - 632004, Tamil Nadu, India.
Department of Haematology, Christian Medical College, Ida Scudder Road, Vellore - 632004, Tamil Nadu, India.
Transplant Cell Ther. 2021 May;27(5):409.e1-409.e6. doi: 10.1016/j.jtct.2021.01.029. Epub 2021 Feb 6.
Allogeneic hematopoietic stem cell transplantation (HSCT) using fludarabine (Flu)-based conditioning regimens are being increasingly being used in patients with aplastic anemia (AA). We describe an antithymocyte globulin (ATG)-free conditioning regimen consisting of Flu and cyclophosphamide (Cy) in patients undergoing matched related donor (MRD) HSCT for AA. Between 2004 and 2019, 212 patients underwent MRD HSCT using Flu (30 mg/m/day for 6 days) and Cy (60 mg/kg/day for 2 days) for conditioning. The graft source was peripheral blood stem cells in all patients. Graft-versus-host disease (GVHD) prophylaxis consisted mainly of cyclosporine and methotrexate, although 41 patients received post-transplantation Cy as part of a study. Engraftment occurred in 91% of patients at a median of 16 days, whereas 4 patients (1.8%) experienced primary graft failure and 15 (7.1%) died before achieving engraftment. Toxicity was minimal. The incidence of grade II-IV acute GVHD (aGVHD) was 27.9%, and that of grade III-IV aGVHD was 11.3%. Chronic GVHD occurred in 41.6%. 80% were free of immunosuppression at 60 months and long-term complications were seen in 8.4%. At a median of 46 months, 158 patients were alive and well, with a 5-year overall survival (OS) of 75.3 ± 3.0%. The 5-year OS was 80.6 ± 4.1% for patients age <20 years (n = 93), 74.5 ± 4.6% for those age 20 to 40 years (n = 91), and 59.7 ± 9.5% for those age >40 years (n = 28) (P = .11). Patients classified as low risk had better OS compared with those at high risk (93.2 ± 2.9% versus 65.7 ± 4.1%; P = .000). Factors affecting OS on multivariate analysis included aGVHD (P = .02) and graft failure (P = .000). This large series using Flu/Cy for conditioning before MRD HSCT confirms good outcomes in patients with AA, with excellent outcomes in low-risk patients. Suitable modifications are needed to improve outcomes in high-risk patients.
同种异体造血干细胞移植（HSCT）使用基于氟达拉滨（Flu）的预处理方案，越来越多地用于治疗再生障碍性贫血（AA）患者。我们描述了一种无抗胸腺细胞球蛋白（ATG）的预处理方案，该方案由 Flu（6 天，每天 30mg/m）和环磷酰胺（Cy）组成，用于接受匹配相关供体（MRD）HSCT 的 AA 患者。在 2004 年至 2019 年期间，212 名患者接受了 Flu（6 天，每天 30mg/m）和 Cy（2 天，每天 60mg/kg）的 MRD HSCT。所有患者的移植物来源均为外周血干细胞。移植物抗宿主病（GVHD）预防主要包括环孢素和甲氨蝶呤，但 41 名患者接受了移植后 Cy 治疗，作为一项研究的一部分。91%的患者在中位数为 16 天的时间内实现了嵌合，而 4 名患者（1.8%）发生了原发性移植物失败，15 名患者（7.1%）在实现嵌合前死亡。毒性极小。Ⅱ-Ⅳ级急性 GVHD（aGVHD）的发生率为 27.9%，Ⅲ-Ⅳ级 aGVHD 的发生率为 11.3%。慢性 GVHD 发生率为 41.6%。80%的患者在 60 个月时无需免疫抑制，8.4%的患者出现长期并发症。在中位数为 46 个月时，158 名患者存活且状况良好，5 年总生存率（OS）为 75.3±3.0%。年龄<20 岁（n=93）、20-40 岁（n=91）和>40 岁（n=28）患者的 5 年 OS 分别为 80.6±4.1%、74.5±4.6%和 59.7±9.5%（P=0.11）。低危患者的 OS 优于高危患者（93.2±2.9%与 65.7±4.1%；P=0.000）。多变量分析显示影响 OS 的因素包括 aGVHD（P=0.02）和移植物衰竭（P=0.000）。这项使用 Flu/Cy 预处理后进行 MRD HSCT 的大型系列研究证实了 AA 患者接受该方案的良好预后，低危患者的预后极好。需要适当的调整以改善高危患者的预后。
