BACKGROUND There have been concerns regarding increased peritransplantation complications, especially severe acute graft-versus-host disease (aGVHD), in patients with prior use of checkpoint inhibitors (CPI) before hematopoietic stem cell transplantation (HSCT). METHODS The authors performed a retrospective study of 43 patients with acute myeloid leukemia and/or myelodysplastic syndromes who were treated with an antiprogrammed cell death protein 1 (PD-1) (32 patients) or anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (9 patients) blockade or both (2 patients) prior to HSCT with the primary outcome of aGVHD by day 100 after HSCT. Outcome analyses were stratified by GVHD prophylaxis as use of post-HSCT cyclophosphamide (PTCy) (22 patients) or not (non-PTCy) (21 patients). RESULTS The PTCy group demonstrated a trend toward lower grade 3 to 4 aGVHD when compared with the non-PTCy group (5% vs 22%), although the rates of grade 2 to 4 aGVHD were comparable (49% vs 56%). The interval between CPI and HSCT did not appear to impact the incidence of aGVHD. However, a higher incidence of grade 3 to 4 aGVHD was observed in patients who received >4 treatments of CPI prior to HSCT if they were not given PTCy as GVHD prophylaxis (43% vs 12%). Matched control analyses using patients with no prior use of CPI confirmed the increase in grade 3 to 4 aGVHD with those agents. However, that increased risk was limited to patients who did not receive PTCy and was not observed in patients who received PTCy as GVHD prophylaxis. Despite persistent improvement in GVHD with the use of PTCy, disease control was not compromised and progression-free survival at 1 year was found to be superior for patients treated with PTCy compared with those not receiving PTCy among patients with prior use of CPI (55% vs 22%). CONCLUSIONS The results of the current study indicated that HSCT with prior use of CPI appears feasible in patients with acute myeloid leukemia and/or myelodysplastic syndromes and the use of PTCy as GVHD prophylaxis improves outcomes.

中文翻译：

---

移植后环磷酰胺可改善接受检查点抑制剂治疗的AML / MDS患者的移植结果。

背景技术在造血干细胞移植（HSCT）之前事先使用检查点抑制剂（CPI）的患者中，有关移植周围并发症增加的担忧，尤其是严重的急性移植物抗宿主病（aGVHD）。方法作者对43例急性髓细胞性白血病和/或骨髓增生异常综合征患者进行了回顾性研究，他们接受了抗程序性细胞死亡蛋白1（PD-1）（32例）或抗细胞毒性T淋巴细胞相关蛋白4（CTLA- 4）HSCT之前（9例）阻塞或两者（2例）阻塞，HSCT后第100天主要结果为aGVHD。通过GVHD预防对结果分析进行分层，即使用HSCT后使用环磷酰胺（PTCy）（22例）或不使用（非PTCy）（21例）。结果与非PTCy组相比，PTCy组显示出3至4级aGVHD降低的趋势（5％对22％），尽管2至4级aGVHD的发生率具有可比性（49％对56％）。CPI和HSCT之间的间隔似乎并未影响aGVHD的发生率。但是，如果在未接受PTCy预防GVHD的情况下对HSCT进行CPI治疗> 4的患者，则观察到3至4级aGVHD的发生率较高（43％比12％）。使用未曾使用CPI的患者进行的对照分析证实，这些药物可使3至4级aGVHD升高。但是，这种增加的风险仅限于未接受PTCy的患者，未在接受PTCy作为GVHD预防的患者中未观察到。尽管使用PTCy可以持续改善GVHD，在先前使用CPI的患者中，与未接受PTCy的患者相比，接受PTCy治疗的患者的疾病控制没有受到损害，并且1年无进展生存率更高（55％对22％）。结论当前研究的结果表明，事先使用CPI的HSCT在急性髓细胞性白血病和/或骨髓增生异常综合症患者中似乎是可行的，并且使用PTCy预防GVHD可改善预后。