Rosales F, Naparstek E, Varadi G, Or R, Slavin S, Nagler A
Department of Bone Marrow Transplantation and The Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel.
Leuk Res. 1999 Oct;23(10):947-52. doi: 10.1016/s0145-2126(99)00112-5.
Graft versus host disease (GVHD) and recurrence of basic disease are major obstacles to a successful allogeneic bone marrow transplantation (BMT) outcome. One of the possibilities of maintaining the therapeutic potential of marrow allografting in the absence of GVHD is to intensify the conditioning regimen administered pre-T-cell depleted BMT in order to compensate for the loss of GVH related graft versus leukemia (GVL) effect. In order to do so we used a preparative regimen consisting of three alkylating agents-Busulfan (BU), Thiotepa (TTP) and Cyclophosphamide (CY)-for T-cell depleted allogeneic stem cell transplantation (SCT) instead of the standard BU-CY protocol. The effect of this intensified regimen was investigated in 30 consecutive leukemia patients who underwent T-cell depleted SCT from HLA identical siblings. Sixteen of the patients were males and 14 females, of median age 24 (5-43) years. Fourteen patients had acute myelogenous leukemia (AML), ten acute lymphoblastic leukemia (ALL), four chronic myelogenous leukemia (CML) and two myelodysplastic syndrome. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was normal, with WBC >1.0x10(9)/l at day +18 (10-32), ANC >0.5x10(9)/l at day +21 (9-33) and platelets >25x10(9)/l at day +30 (14-69). Regimen related toxicity (RRT) was moderate and transplant related complications comparable to other conventional conditioning protocols. Overall survival and disease free survival (DFS) at 60 months follow up was 50%. Only three patients (10%), with ALL, relapsed and subsequently died. From the current data it would appear that TTP does not significantly improve BMT outcome in patients with leukemia, when compared to the standard BU-CY conditioning. However, our results with the BU-TTP-CY combination followed by T-cell depleted allogeneic SCT could provide the basis for a prospective randomized study comparing this protocol with the standard BU-CY regimen.
移植物抗宿主病（GVHD）和基础疾病的复发是异基因骨髓移植（BMT）成功的主要障碍。在不发生GVHD的情况下维持骨髓移植治疗潜力的一种可能性是强化在去除T细胞的BMT之前给予的预处理方案，以弥补GVH相关的移植物抗白血病（GVL）效应的损失。为了做到这一点，我们使用了一种由三种烷化剂——白消安（BU）、噻替派（TTP）和环磷酰胺（CY）组成的预处理方案，用于去除T细胞的异基因干细胞移植（SCT），而不是标准的BU - CY方案。在30例接受来自HLA相同同胞的去除T细胞的SCT的连续白血病患者中研究了这种强化方案的效果。患者中16例为男性，14例为女性，中位年龄24（5 - 43）岁。14例患者患有急性髓性白血病（AML），10例患有急性淋巴细胞白血病（ALL），4例患有慢性髓性白血病（CML），2例患有骨髓增生异常综合征。预处理方案包括：BU 4 mg/kg×4天（-8至-5），TTP 5 mg/kg×2天（-4和-3），以及CY 60 mg/kg×2天（-2和-1）。造血重建正常，在第18天（10 - 32）时白细胞>1.0×10⁹/L，在第21天（9 - 33）时中性粒细胞>0.5×10⁹/L，在第30天（14 - 69）时血小板>25×10⁹/L。方案相关毒性（RRT）为中度，与其他传统预处理方案相当的移植相关并发症。60个月随访时的总生存率和无病生存率（DFS）为50%。只有3例（10%）ALL患者复发并随后死亡。从目前的数据来看，与标准的BU - CY预处理相比，TTP在白血病患者中似乎并没有显著改善BMT的结果。然而，我们使用BU - TTP - CY联合方案随后进行去除T细胞的异基因SCT的结果可为将该方案与标准BU - CY方案进行比较的前瞻性随机研究提供依据。
