Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Duesseldorf, Germany.
Biol Blood Marrow Transplant. 2012 Mar;18(3):466-72. doi: 10.1016/j.bbmt.2011.09.006. Epub 2011 Sep 29.
Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients received high-dose melphalan alone (200 mg/m(2) for patients with an age <50 years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 100 mg/m(2) for patients with an age >60 years; n = 24) or melphalan and thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All patients except 1 with primary graft failure achieved complete remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years, overall survival, event-free survival, and treatment-related mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part of the conditioning regimen. Our results add to the body of evidence that a FLAMSA-based sequential conditioning therapy is effective for previously untreated patients with high-risk MDS or sAML.
患者患有高风险骨髓增生异常综合征（MDS）或继发于 MDS 的急性髓性白血病（AML）（sAML），其对常规细胞毒性化疗的反应较差。我们前瞻性单中心研究的目的是检查异基因造血干细胞移植（HSCT）作为未经治疗的高危 MDS 或 sAML 患者一线治疗的安全性和有效性。在 2003 年 11 月至 2010 年 6 月期间，30 名患者（20 名高危 MDS，10 名 sAML）接受氟达拉滨（4×30mg/m2）、胺苯吖啶（4×100mg/m2）和阿糖胞苷（4×2g/m2，FLAMSA）治疗。休息 2 至 3 天后，患者单独接受大剂量马法兰（年龄<50 岁的患者 200mg/m2，年龄在 50 至 60 岁之间的患者 150mg/m2，年龄>60 岁的患者 100mg/m2；n=24）或马法兰和噻替哌（10mg/kg，Mel/Thio，n=6）。在这些大剂量条件化方案之后，中位数为 7.7×106CD34+细胞/kg 体重（范围：2.9×106-17.2×106）从 13 名相关供体或 17 名无关供体中移植。抗胸腺细胞球蛋白（Fresenius 30-60mg/kg）以及他克莫司和霉酚酸酯用于移植物抗宿主病（GVHD）预防。除 1 例原发性移植物失败外，所有患者在 HSCT 后均获得完全缓解。在中位数为 28 个月（范围：7-81）的随访后，21 名患者（70%）存活且无疾病。总体而言，有 4 名患者复发。在 2 年时，总生存率、无事件生存率和治疗相关死亡率分别为 70%、63%和 30%。由于毒性过大，噻替哌不再是条件化方案的一部分。我们的结果为基于 FLAMSA 的序贯预处理治疗在未经治疗的高危 MDS 或 sAML 患者中的有效性提供了更多证据。
