Treosulfan vs busulfan-based conditioning regimens in allo-HSCT for patients with MF: an EBMT study

Several conditioning regimens are available for patients with myelofibrosis (MF) who will undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) in order to manage splenomegaly, hepatic disease, and graft rejection. While busulfan-based conditioning regimens are used frequently, no single conditioning regimen has yet been defined as being the most effective.

Below, we summarize a retrospective analysis by Robin et al.¹ published in Nature on March 15, 2024, investigating treosulfan-based regimens compared with busulfan-based regimens in patients with MF who will undergo allo-HSCT from the European Bone Marrow Transplant (EBMT) registry.

Study design¹

• This multicenter analysis included patients who underwent transplant during 2010–2018 for primary MF, post polycythemia vera, or essential thrombocythemia MF and received treosulfan- or busulfan-based conditioning regimens.
  • Busulfan-based regimens were required to be administered intravenously.
• Transplant centers were part of the EBMT registry, located mostly in Europe.
• The primary endpoints were overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse and non-relapse mortality post transplantation.
• Other endpoints included cumulative incidence of engraftment and acute or chronic graft-versus-host disease (GvHD).

Key findings¹

• Overall, 530 patients were included: 457 received busulfan and 73 received treosulfan.
  • Among patients who received busulfan, 134 received a low dose (≤6.4 mg/kg) and 57 received a high dose (≥12.8 mg/kg).
• The median age was lower in patients with low-dose busulfan and treosulfan compared with high-dose busulfan (56 years, 59 years and 61 years, respectively).
• MF classification, period of transplant, splenomegaly, MF-related symptoms, GvHD prophylaxis, and use of in vivo T-cell depletion were well matched between subgroups.

Results¹

• The median time to neutrophil recovery was similar in the low-dose busulfan, high-dose busulfan, and treosulfan recipients (15, 16, and 14 days, respectively).
• The cumulative incidence of patients receiving a second allo-HSCT was also similar between groups (11%, 9%, and 9% respectively).
• Patients treated with treosulfan prior to transplant experienced increased PFS compared with both busulfan doses (Figure 1):
  • OS was also higher in patients treated with treosulfan compared with high-dose busulfan; but
  • Relapse rates were similar across cohorts.

GvHD, graft-versus-host disease; HD, high-dose; LD, low-dose; NRM, non-relapse mortality; PFS, progression-free survival; OS, overall survival.  
*Adapted from Robin et al.¹   

• In total, 233 deaths were reported, with most attributed to non-relapse mortality.
• GvHD leading to death was less common with low-dose busulfan and treosulfan compared with high-dose busulfan (21.7% and 22.2% vs 32.9%).

Key learnings

Treosulfan-based conditioning regimens for patients with MF compared favorably against busulfan-based conditioning regimens, especially in terms of PFS and OS. Non-relapse mortality was similar with low-dose busulfan conditioning regimens vs high-dose busulfan regimens, and busulfan intensity may not impact majorly on general outcome – indicating the need to reexamine dosing guidelines. Studies with greater patient numbers and more homogeneous data are needed to confirm these findings.