Gaziev Javid, Isgrò Antonella, Sodani Pietro, Marziali Marco, Paciaroni Katia, Gallucci Cristiano, De Angelis Gioia, Andreani Marco, Testi Manuela, Alfieri Cecilia, Ribersani Michela, Galluccio Tiziana, Battarra Maria Rosa, Morrone Aldo, Lucarelli Guido
1 International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy.
Transplantation. 2016 Apr;100(4):925-32. doi: 10.1097/TP.0000000000000928.
Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol.
Sixty-three patients between 5 and 16.7 years of age with class 3 thalassemia received HLA-matched sibling BMT following either the original protocol (26 patients) or the modified protocol (37 patients). Both regimens comprised preconditioning cytoreduction with hydroxyurea and azathioprine starting at -45 days pretransplant, and fludarabine from days -16 to -12. Conditioning was performed with busulfan and cyclophosphamide (original protocol) or with busulfan, thiotepa, and cyclophosphamide (modified protocol).
The 2 groups showed similar patient demographics. At day 0, the degree of cytoreduction (lymphopenia, neuthropenia, and thrombocytopenia) achieved by the modified protocol was greater than the original protocol. The incidence of graft failure/rejection was significantly higher in the original group (15%; 95% confidence interval [95% CI], 5-32%) compared with the modified group (0%) (P = 0.014). The respective 5-year thalassemia-free survival rates were 73% (95% CI, 51-86%) and 92% (95% CI, 77-97%) (P = 0.047). Both groups showed similar incidences of grades II to IV acute graft-versus host disease. Modified protocol did not increase nonhematological toxicity or infectious complications.
The modified treatment protocol effectively and safely prevented graft failure/rejection and significantly increased thalassemia-free survival of class 3 patients with thalassemia.
由于移植排斥率和移植相关死亡率较高，对3级地中海贫血患者进行骨髓移植（BMT）具有挑战性。自20世纪80年代末首次开展BMT研究以来，已经设计了多种预处理方案以改善治疗效果，但结果并不理想。在此，我们报告采用改良方案对3级患者进行移植的结果。
63例年龄在5至16.7岁之间的3级地中海贫血患者接受了 HLA 匹配的同胞BMT，其中26例患者采用原方案，37例患者采用改良方案。两种方案均包括在移植前-45天开始使用羟基脲和硫唑嘌呤进行预处理细胞减少，以及在-16至-12天使用氟达拉滨。预处理采用白消安和环磷酰胺（原方案）或白消安、噻替派和环磷酰胺（改良方案）。
两组患者的人口统计学特征相似。在第0天，改良方案实现的细胞减少程度（淋巴细胞减少、中性粒细胞减少和血小板减少）大于原方案。原方案组的移植失败/排斥发生率（15%；95%置信区间[95%CI]，5-32%）显著高于改良方案组（0%）（P = 0.014）。相应的5年无地中海贫血生存率分别为73%（95%CI，51-86%）和92%（95%CI，77-97%）（P = 0.047）。两组II至IV级急性移植物抗宿主病的发生率相似。改良方案未增加非血液学毒性或感染并发症。
改良治疗方案有效且安全地预防了移植失败/排斥，并显著提高了3级地中海贫血患者的无地中海贫血生存率。
