Bautista G, Regidor C, Gonzalo-Daganzo R, Cabrera J R
Servicio de Hematología, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, España.
Methods Find Exp Clin Pharmacol. 2010 Dec;32 Suppl A:47-51.
Our team conducted an original procedure of hematopoietic transplantation of umbilical cord blood (UCB) from an unrelated donor. The procedure consists of co-infusing hematopoietic stem cells selected from the blood of a third-party donor; it is conceived as a tool to shorten the engraftment period without preventing the engraftment of the UCB, even when using units with relatively low cell content and a low HLA compatibility. Between 1999 and 2008 we performed 64 transplantations in 60 adult patients (35 men and 25 women) with a median age of 34 years (range: 76-60) and a median weight of 70 kg (range: 43-95), all of whom were diagnosed with a high risk hematologic neoplasm (leukemia in most cases). Fludarabine, cyclophosphamide, ATG, and whole body irradiation or busulfan were used as conditioners. UCB was infused at medians of 2.4 x 107 CNT/kg (range: 1.14-4.30 x 107), 0.11 x 106 CD34+/kg (range: 0.035-0.37 x 106). Then, hematopoietic stem cells selected from the third-party donor were infused (2.43 x 106/kg [range: 1.05-3.34 x 106], with 0.3 x 104 CD3+/kg [range: 0.05-1.56 x 104]). Granulocyte engraftment occurred (ANC > 0.5 x 109/L) at a median of 10 days (range: 9-34 days), and the granulocyte engraftment of the UCB occurred in 21 days (range: 13-57 days). Complete UCB chimerism was observed in 37 days (range: 11-186 days) (previously double complete chimerism, presence of third-party donor and of cord) and platelet engraftment > 20 x 109/L in 33 days (range: 13 98 days) and > 50 x 109/L in 58 days (range: 14-106 days). Overall 3-year survival reached 51%, and 5 10 year-survival was 47% (plateau). Disease-free survival was 48% at three years, and 45% at 5 to 10 years; the mean follow-up of survivors was 48 months (range: 13-123 months). (Kaplan-Meier). In conclusion, early granulocyte recovery occurred thanks to a foster engraftment of hematopoietic stem from the third-party donor, which are not HLA-restricted; this is associated with a lower morbidity and mortality from infections secondary to neutropenia. There was also a high rate of engraftment and final full UCB chimerism, even with non-histocompatible UCB units (2/6 HLA mismatches) and with relatively low cell counts. In most cases, a single unit of UCB was sufficient. The incidence of severe GVHD and the percentage of relapses have been low. Opportunistic infections have occurred over a long period of time. This procedures makes allogeneic hematopoietic transplantation accessible to almost all patients.
我们的团队开展了一项无关供者脐血造血移植的原创性程序。该程序包括共同输注从第三方供者血液中筛选出的造血干细胞；其被设想为一种即使在使用细胞含量相对较低且HLA相容性较差的脐血单位时，也能缩短植入期且不阻碍脐血植入的工具。1999年至2008年期间，我们对60例成年患者（35例男性和25例女性）进行了64例移植，患者中位年龄34岁（范围：60 - 76岁），中位体重70 kg（范围：43 - 95 kg），所有患者均被诊断为高危血液系统肿瘤（大多数病例为白血病）。氟达拉滨、环磷酰胺、抗胸腺细胞球蛋白及全身照射用作预处理方案。脐血输注的中位数为2.4×10⁷个有核细胞/kg（范围：1.14 - 4.30×10⁷）、0.11×10⁶个CD34⁺细胞/kg（范围：0.035 - 0.37×10⁶）。然后，输注从第三方供者筛选出的造血干细胞（2.43×10⁶/kg [范围：1.05 - 3.34×10⁶]，含0.3×10⁴个CD3⁺细胞/kg [范围：0.05 - 1.56×10⁴]）。粒细胞植入（中性粒细胞绝对值>0.5×10⁹/L）的中位时间为10天（范围：9 - 34天），脐血的粒细胞植入发生在21天（范围：13 - 57天）。完全脐血嵌合在37天（范围：11 - 186天）时观察到（之前为双完全嵌合，存在第三方供者和脐血），血小板植入>20×10⁹/L在33天（范围：13 - 98天），>50×10⁹/L在58天（范围：14 - 106天）。总体3年生存率达51%，5至10年生存率为47%（平台期）。3年无病生存率为48%，5至10年为45%；存活者的平均随访时间为48个月（范围：13 - 123个月）。（Kaplan - Meier法）。总之，由于第三方供者的造血干细胞的促进植入（其不受HLA限制），早期粒细胞得以恢复；这与中性粒细胞减少继发感染导致的较低发病率和死亡率相关。即使使用非组织相容性的脐血单位（2/6 HLA错配）且细胞计数相对较低，也有较高的植入率和最终完全脐血嵌合率。在大多数情况下，单单位脐血就足够了。严重移植物抗宿主病的发生率和复发率一直较低。机会性感染在较长时间内发生。该程序使几乎所有患者都能接受异基因造血移植。
