Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia
Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia
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DOI：
10.1007/s00277-003-0654-9
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发表时间：
2003-06-01
影响因子：
3.5
通讯作者：
Zander, AR
中科院分区：
文献类型：
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作者：
Kröger, N;Bornhäuser, M;Zander, AR
我们报告了37例骨髓增生异常综合征（MDS）或继发性急性髓性白血病（sAML）患者的可行性和有效性，这些患者不符合标准清髓性预处理方案的条件，采用氟达拉滨/白消安为基础的剂量减少预处理方案，随后进行相关（n=19）或无关HLA匹配供体（n=18）的干细胞移植。预处理方案包括氟达拉滨（120-180 mg/m2）、白消安（8 mg/kg p.o.或6.4 mg/kg i.v.），抗胸腺细胞球蛋白（n=25）。移植物抗宿主病（GVHD）预防包括环孢素（n=36）和短期甲氨蝶呤（n=29）或霉酚酸酯（n=3）。患者的中位年龄为55岁（范围：23-72岁）。进行剂量降低预处理的原因是体能状态降低（n=14）、年龄（n=12）、既往自体（n=5）或同种异体（n=1）移植或既往/活动性真菌感染（n=5）。移植时诊断为难治性贫血（RA）（n=8）、难治性贫血伴原始细胞过多（RAEB）（n=6）、RAEB转化（RAEB-T）（n=13）、慢性粒单核细胞白血病（CMML）（n=3）和sAML（n=7）。干细胞来源为外周血干细胞（PBSC）（n=29）或骨髓（n=8）。1例患者接受了T细胞耗竭的外周干细胞移植。观察到2例初次移植失败（6%）。中位14天后，观察到白细胞（> 1.0 × 10（9）/l）和血小板（> 20 × 10（9）/l）植入。急性GVHD II-IV级见于37%，而严重的III/IV级GVHD见于6例患者（17%）。慢性GVHD 13例（48%）。有10例死亡（27%）是由于治疗（TRM）。与低或中等核型的患者相比，无关供体患者（45 vs 12%，p=0.03）和细胞遗传学较差的患者TRM的概率更高（75 vs 20%，p=0.009）。随访期间12例患者复发（32%）。与慢性GVHD患者相比，无慢性GVHD患者的复发概率显著更高（70 vs 15%，p=0.02）。中位随访20个月后，3年估计无病生存率（DFS）为38% [95%置信区间（CI）：21-55%]，总生存率（OS）为39%（95% CI：22-56%）。相关和非相关移植后的OS和DFS分别为45%（95% CI：19-71%）和31%（95% CI：9-53%）（n.s.）和51%（95% CI：29-73%）vs 25%（95% CI：4-47%）（n.s.），分别我们的结论是，减少剂量的预处理，然后从相关或无关的供体异基因干细胞移植是一种有效的治疗方法，MDS/sAML患者，并可能治愈大量的患者谁是不符合标准的异基因移植。
We report the feasibility and efficacy of a fludarabine/busulfan-based dose-reduced conditioning regimen followed by stem cell transplantation from related (n=19) or unrelated HLA-matched donors (n=18) in 37 patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine (120-180 mg/m(2)), busulfan (8 mg/kg p.o. or 6.4 mg/kg i.v.), and antithymocyte globulin (n=25). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (n=36) and a short course of methotrexate (n=29) or mycophenolate mofetil (n=3). The median age of the patients was 55 years (range: 23-72). The reasons to perform a dose-reduced conditioning were reduced performance status (n=14), age (n=12), prior autologous (n=5) or allogeneic (n=1) transplantation, or prior/active fungal infection (n=5). Diagnoses at transplantation were refractory anemia (RA) (n=8), refractory anemia with excess of blasts (RAEB) (n=6), RAEB in transformation (RAEB-T) (n=13), chronic myelomonocytic leukemia (CMML) (n=3), and sAML (n=7). Stem cell sources were peripheral blood stem cells (PBSC) (n=29) or bone marrow (n=8). One patient received a T-cell-depleted peripheral stem cell graft. Two primary graft failures were observed (6%). Engraftment of leukocytes (>1.0x10(9)/l) and platelets (>20x10(9)/l) was seen after a median of 14 days. Acute GVHD grade II-IV was seen in 37%, while severe grade III/IV GVHD was observed in six patients (17%). Chronic GVHD was seen in 13 patients (48%). There were ten deaths (27%) due to treatment (TRM). The probability of TRM was higher in patients with unrelated donors (45 vs 12%, p=0.03) and in patients with poor cytogenetics in comparison to those with a low or intermediate karyotype (75 vs 20%, p=0.009). During follow-up 12 patients relapsed (32%). Patients without chronic GVHD had a significantly higher probability of relapse compared to those with chronic GVHD (70 vs 15%, p=0.02). After a median follow-up of 20 months, the 3-year estimated disease-free survival (DFS) is 38% [95% confidence interval (CI): 21-55%] and the overall survival (OS) is 39% (95% CI: 22-56%). The OS and DFS after related and unrelated transplantations was 45% (95% CI: 19-71%) vs 31% (95% CI: 9-53%) (n.s.) and 51% (95% CI: 29-73%) vs 25% (95% CI: 4-47%) (n.s.), respectively. We conclude that dose-reduced conditioning followed by allogeneic stem cell transplantation from related or unrelated donors is an effective treatment approach in patients with MDS/sAML and might cure a substantial number of patients who are not eligible for a standard allogeneic transplantation.