Lacerda J F, Martins C, Carmo J A, Lourenço F, Juncal C, Rodrigues A, Vilalobos I, Moura M C, Ligeiro D, Martinho A, Lacerda J M F
Bone Marrow Transplant Unit, Med IIIA, University of Lisbon, Santa Maria Hospital, Av. Prof. Egas Moniz, 1600 Lisbon, Portugal.
Biol Blood Marrow Transplant. 2003 Oct;9(10):633-42. doi: 10.1016/s1083-8791(03)00263-5.
We investigated whether a novel chemotherapy-alone conditioning regimen would permit durable engraftment of standard doses of CD34+ purified stem cell grafts from full-haplotype mismatched related donors. We also examined the role of infusing limited doses of donor leukocytes for prevention of leukemia relapse. Our conditioning regimen consisted of thiotepa, fludarabine, rabbit antithymocyte globulin, melphalan, cyclosporin, and prednisolone. Since October 1998, 14 patients with high-risk leukemia were treated; 13 donor-patient pairs shared 3 of 6 HLA antigens, and 1 pair shared 5 of 6 HLA antigens. A median of 5.4 x 10(6) CD34+ cells per kilogram, 1.62 x 10(4) CD3+ cells per kilogram, and 9.32 x 10(4) CD19+ cells per kilogram were infused. T-cell depletion was the only graft-versus-host disease (GVHD) prophylaxis. All patients had prompt engraftment, and no late graft rejections were observed. All surviving patients received at least 1 infusion of donor whole blood containing 5, 7, 10, 25, or 50 x 10(3) CD3+ cells per kilogram between days 25 and 95 after transplantation, after which 8 developed acute GVHD (3 grade I, 2 grade II, 2 grade III, and 1 grade IV) and 2 developed a bronchiolitis obliterans-like syndrome. After attaining complete remission, 5 patients relapsed and died with active leukemia. The estimated relapse-related mortality at 4 years is 38.1%. As of June 15, 2003, 6 of 14 patients have survived a median of 43.5 months after transplantation with 100% donor cells. All 6 surviving patients developed acute GVHD and had a natural killer cell mismatch with their donors in the direction of graft versus host. The estimated overall survival and event-free survival for the 14 patients at 4 years is 41.7% +/- 13.5%.
我们研究了一种新型的单纯化疗预处理方案是否能使全单体型不匹配相关供者的标准剂量CD34+纯化干细胞移植物实现持久植入。我们还研究了输注有限剂量供者白细胞在预防白血病复发中的作用。我们的预处理方案包括噻替派、氟达拉滨、兔抗胸腺细胞球蛋白、美法仑、环孢素和泼尼松龙。自1998年10月以来，14例高危白血病患者接受了治疗；13对供受者共享6个HLA抗原中的3个，1对共享6个HLA抗原中的5个。每千克中位输注5.4×10⁶个CD34+细胞、1.62×10⁴个CD3+细胞和9.32×10⁴个CD19+细胞。去除T细胞是预防移植物抗宿主病（GVHD）的唯一措施。所有患者均迅速植入，未观察到晚期移植物排斥反应。所有存活患者在移植后第25天至95天之间至少接受1次每千克含5、7、10、25或50×10³个CD3+细胞的供者全血输注，之后8例发生急性GVHD（3例I级、2例II级、2例III级和1例IV级），2例发生闭塞性细支气管炎样综合征。达到完全缓解后，5例患者复发并死于活动性白血病。4年时估计的复发相关死亡率为38.1%。截至2003年6月15日，14例患者中有6例在移植后中位存活43.5个月，体内有100%的供者细胞。所有6例存活患者均发生急性GVHD，且自然杀伤细胞与供者在移植物抗宿主方向上不匹配。14例患者4年时估计的总生存率和无事件生存率为41.7%±13.5%。
