祛铁治疗对伴铁过载骨髓增生异常综合征患者异基因造血干细胞移植的影响

Effects of iron chelation therapy on allogeneic hematopoietic stem cell transplantation in myelodysplastic syndrome patients with iron overload

目的探讨祛铁治疗对骨髓增生异常综合征（MDS）患者异基因造血干细胞移植（allo-HSCT）后造血重建和相关并发症的影响。方法回顾性分析57例伴铁过载的allo-HSCT治疗的MDS患者的临床资料，根据血清铁蛋白（SF）水平分为有效祛铁组（移植前SF 〈1 000 μg/L）和铁过载组（移植前SF≥1 000 μg/L）。探讨有效祛铁治疗对移植后造血重建及相关并发症的影响。结果①57例患者中30例在移植前行祛铁治疗，27例未行祛铁治疗。30例行祛铁治疗的患者中19例（63%）归入有效祛铁组[移植前SF中位数为561（223-846）μg/L]，11例归入铁过载组[移植前SF中位数为1 262 （1 100-2 352）μg/L]。27例未行祛铁治疗患者移植前SF中位数为1 540（1 320-3 112）μg/L，均归入铁过载组。②有效祛铁组、铁过载组分别有19例（100.0%）、34例（89.5%）获得干细胞完全植入，粒系重建时间分别为12（10-18） d、12（11-30） d（P=0.441），血小板重建时间分别为13（12-30） d、15（10-32） d（P= 0.579）。③有效祛铁组感染发生率低于铁过载组[36.8%（7/19）对82.4%（28/34），P=0.002]。④有效祛铁组急性移植物抗宿主病（aGVHD）发生率低于铁过载组[26.3%（5/19）对64.7%（22/34），P=0.010]。有效祛铁组aGVHD均为Ⅰ/Ⅱ度，铁过载组Ⅰ/Ⅱ、Ⅲ/Ⅳ度患者分别为16、6例。⑤铁过载组6例患者移植后早期继续祛铁治疗，SF由2 870 （2 205-3 580）μg/L降至1 270 （1 020-1 650）μg/L，且耐受性良好。⑥有效祛铁组中位无病生存时间与铁过载组比较，差异无统计学意义[28.9 （0.3-89.5）个月对21.2（0.1-81.0）个月，χ2=3.751，P=0.053]。结论铁过载显著增加MDS患者移植相关并发症；移植前有效的祛铁治疗可明显降低移植后感染及aGVHD发生率和严重程度。

ObjectiveTo investigate the effects of iron chelation therapy on hematopoietic reconstitution and related complications of allogeneic hematopoietic stem cell transplantation （allo-HSCT） in patients with myelodysplastic syndrome （MDS）.MethodsVarious clinical parameters were analyzed retrospectively in 57 MDS patients with iron overload who received allo-HSCT. According to the level of serum ferritin （SF） before transplantation divided patients into two groups： the effective treatment group （SF〈1 000 μg/L） and iron overload group （SF≥1 000 μg/L）.Results①30/57 cases were received iron chelation treatment, 27/57 patients didn＇ t received iron chelating therapy before transplantation. 19/30 cases were in the effective treatment group, and the median SF level before transplantation was 561 （223-846） μg/L. 11/30 cases were in the iron overload group, and the median SF level before transplantation was 1 262 （1 100-2 352） μg/L. The median SF level was 1 540 （1 320-3 112） μg/L of 27 patients didn＇t received iron chelating therapy before transplantation. ② The rate of fully-engraftment in the effective treatment group and iron overload group was 19 cases （100.0% ） and 34 cases （89.5% ）, myeloid reconstitution of 12（10-18） and 12（11-30） days respectively （P=0.441）, and platelet reconstitution of 13（12-30） and 15 （10-32） days respectively （P=0.579）. ③The infection risk rate of the effective treatment group was less than iron overload group [36.8% （7/19） vs 82.4% （28/34）, P=0.002]. ④The incidence of aGVHD in effective treatment group was less than iron overload group [26.3%（5/19） vs 64.7%（22/34）, P= 0.010]. All patients of the effective treatment group were Ⅰ/Ⅱ degree. 16 cases were Ⅰ/Ⅱ degree and 6 cases were Ⅲ/Ⅳ degree in the iron overload group. ⑤ 6 cases of iron overload group accepted iron chelation treatment early post-transplantation, and SF level decreased from 2 870 （2 205-3 580） μg/L to 1 270 （1 020-1 650） μg/L. ⑥The difference of median disease-free survival time between the effective treatment group and iron overload group was not statistically significant [28.9 （0.3-89.5） months vs 21.2（0.1-81.0） months, χ2=3.751, P=0.053].ConclusionsIron overload obviously increased transplant-related complications, and effective iron chelation therapy before transplantation significantly decreased the incidence of infection and degree of aGVHD, thereby reduced the non-relapse mortality in patients with MDS.