Kalaycio M, Rybicki L, Pohlman B, Sobecks R, Ball E, Cook D, Andresen S, Kuczkowski E, Bolwell B
Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Bone Marrow Transplant. 2005 Feb;35(3):247-52. doi: 10.1038/sj.bmt.1704736.
The role of T-cell depletion (TCD) to prevent graft-versus-host disease (GVHD) after matched unrelated donor allogeneic bone marrow transplant (MUD BMT) remains undefined. Most studies employ total body irradiation and pan TCD. Between March 1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML) patients with busulfan-based preparative regimens and selective TCD. The preparative regimen consisted of busulfan 14 mg/kg, cyclophosphamide 120 mg/kg and VP-16 50 mg/kg in all but one patient who only received busulfan and cyclophosphamide. Donor marrow was depleted of CD8+ T cells by immunomagnetic bead separation. The patients were also treated with cyclosporine and methylprednisolone or FK-506 and mini-dose methotrexate. Four (15%) of 33 patients developed graft failure or rejection. However, three of these patients were serologically mismatched at HLA-Cw. Although 67% of evaluable patients developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%. The severity of acute GVHD correlated with the degree of CD8+ TCD. Median relapse-free survival was 5 months among 20 patients treated with active AML, and 28 months among 13 patients treated in complete remission. Our results confirm that MUD BMT with CD8+ TCD for AML is a potentially curative treatment option.
在匹配的无关供者异基因骨髓移植(MUD BMT)后,T细胞清除(TCD)预防移植物抗宿主病(GVHD)的作用仍不明确。大多数研究采用全身照射和泛TCD。1993年3月至2002年6月期间,我们用基于白消安的预处理方案和选择性TCD治疗了33例复发的急性髓性白血病(AML)患者。预处理方案包括白消安14mg/kg、环磷酰胺120mg/kg和VP-16 50mg/kg,但有1例患者仅接受了白消安和环磷酰胺。通过免疫磁珠分离去除供体骨髓中的CD8+ T细胞。患者还接受了环孢素和甲泼尼龙或FK-506和小剂量甲氨蝶呤治疗。33例患者中有4例(15%)发生了移植失败或排斥反应。然而,这些患者中有3例在HLA-Cw上血清学不匹配。虽然67%的可评估患者发生了急性GVHD,但严重的III-IV级急性GVHD仅发生在19%的患者中。急性GVHD的严重程度与CD8+ TCD的程度相关。20例活动性AML患者的无复发生存期中位数为5个月,13例完全缓解患者的无复发生存期中位数为28个月。我们的结果证实,AML患者采用CD8+ TCD的MUD BMT是一种潜在的治愈性治疗选择。