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. 2024 Aug 16;16(16):2859.
doi: 10.3390/cancers16162859.

Treosulfan-Versus Melphalan-Based Reduced Intensity Conditioning in HLA-Haploidentical Transplantation for Patients ≥ 50 Years with Advanced MDS/AML

Alessia Fraccaroli  1 , Elena Stauffer  1 , Sarah Haebe  1 , Dusan Prevalsek  1 , Lena Weiss  1 , Klara Dorman  1 , Heidrun Drolle  1 , Michael von Bergwelt-Baildon  1   2 , Hans-Joachim Stemmler  1 , Tobias Herold  1 , Johanna Tischer  1
Affiliations

Treosulfan-Versus Melphalan-Based Reduced Intensity Conditioning in HLA-Haploidentical Transplantation for Patients ≥ 50 Years with Advanced MDS/AML

Alessia Fraccaroli et al. Cancers (Basel). .

Abstract

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/m2) and FC-treosulfan (30 g/m2) 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 (n = 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%, p = 0.8 and p = 0.57). However, FC-melphalan was associated with a significantly lower probability of relapse compared to FC-treosulfan (0% vs. 24%, p = 0.006), counterbalanced by a higher NRM (33% vs. 10%, p = 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.

Keywords: AML; HLA-haploidentical transplantation; MDS; melphalan; sequential therapy; treosulfan.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
CONSORT diagram. Abbreviations: AML, acute myeloid leukemia, HaploT, HLA-haploidentical hematopoietic stem cell transplantation; HCT-CI, hematopoietic cell transplantation-specific comorbidity index, HR, high-risk, HSCT, hematopoietic stem cell transplantation, MDS, myelodysplastic syndrome.
Figure 2
Figure 2
Comparison of transplant outcome following FC-Mel and FC-Treo conditioning regimens ahead of HaploT. Abbreviations: CI, cumulative incidence; FC, combination of fludarabine and cyclophosphamide; HaploT, HLA-haploidentical hematopoietic stem cell transplantation; Mel, melphalan; NRM, non-relapse mortality; Treo, treosulfan.
See this image and copyright information in PMC

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