Fraccaroli Alessia, Stauffer Elena, Haebe Sarah, Prevalsek Dusan, Weiss Lena, Dorman Klara, Drolle Heidrun, von Bergwelt-Baildon Michael, Stemmler Hans-Joachim, Herold Tobias, Tischer Johanna
Hematopoietic Stem Cell Transplantation Unit, Department of Medicine III, LMU University Hospital, 81377 Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, a Partnership between the DKFZ Heidelberg and the University Hospital of the LMU, 81377 Munich, Germany.
Cancers (Basel). 2024 Aug 16;16(16):2859. doi: 10.3390/cancers16162859.
Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable engraftment and low non-relapse mortality (NRM) in patients undergoing HLA-matched allo-HSCT. However, data on treosulfan-based conditioning in the HLA-haploidentical transplantation (HaploT) setting are limited. We retrospectively compared conditioning with fludarabine-cyclophosphamide (FC)-melphalan (110 mg/m) and FC-treosulfan (30 g/m) prior to HaploT using post-transplantation cyclophosphamide (PTCy) in patients with high-risk MDS/AML patients ≥ 50 years, transplanted from 2009-2021 at our institution ( = 80). After balancing patient characteristics by a matched-pair analysis, we identified twenty-one matched pairs. Two-year OS and LFS were similar among the groups (OS 66% and LFS 66%, = 0.8 and = 0.57). However, FC-melphalan was associated with a significantly lower probability of relapse compared to FC-treosulfan (0% vs. 24%, = 0.006), counterbalanced by a higher NRM (33% vs. 10%, = 0.05). Time to engraftment and incidences of acute and chronic graft-versus-host disease (GvHD) did not differ significantly. In conclusion, HaploT using FC-treosulfan in combination with PTCy in patients aged ≥50 years with MDS/AML appears safe and effective, particularly in advanced disease stages. We confirm the favorable extramedullary toxicity profile, allowing for potential dose intensification to enhance antileukemic activity.
复发和方案相关毒性仍然是实现长期生存的主要挑战，尤其是在接受异基因造血干细胞移植（allo-HSCT）的高危骨髓增生异常综合征（MDS）或急性髓系白血病（AML）老年患者中。既往研究已证明基于曲奥舒凡的预处理方案的可行性，指出接受HLA匹配的allo-HSCT患者移植后植入稳定且非复发死亡率（NRM）低。然而，关于基于曲奥舒凡的预处理方案在HLA单倍体相合移植（HaploT）中的数据有限。我们对2009年至2021年在我们机构接受移植的≥50岁高危MDS/AML患者（n = 80）进行回顾性比较，这些患者在HaploT前分别接受氟达拉滨-环磷酰胺（FC）-美法仑（110 mg/m）和FC-曲奥舒凡（30 g/m）预处理，并使用移植后环磷酰胺（PTCy）。通过配对分析平衡患者特征后，我们确定了21对匹配组。两组的两年总生存率（OS）和无白血病生存率（LFS）相似（OS 66%，LFS 66%，P = 0.8和P = 0.57）。然而，与FC-曲奥舒凡相比，FC-美法仑的复发概率显著更低（0%对24%，P = 0.006），但NRM更高（33%对10%，P = 0.05）。植入时间以及急性和慢性移植物抗宿主病（GvHD）的发生率无显著差异。总之，≥50岁MDS/AML患者使用FC-曲奥舒凡联合PTCy进行HaploT似乎安全有效，尤其是在疾病晚期。我们证实了其良好的髓外毒性特征，允许潜在的剂量强化以增强抗白血病活性。
