Home Blog of Signal Transduction DNA Damage/DNA Repair DNA alkylator Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

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Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p<0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p<0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p<0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis.

 

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The optimal conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in myelofibrosis is not well known. A study using the Center for International Blood and Marrow Transplant Research database found that Fludarabine/busulfan is associated with better outcomes in both reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) settings compared to other conditioning regimens, with lower early non-relapse mortality and acute graft versus host disease in RIC and lower acute graft versus host disease and better GVHD-free relapse-free survival in MAC.

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Cat.No. Product Name Information
S1692 Busulfan Busulfan is a cell cycle non-specific alkylating antineoplastic agent. It causes DNA damage by cross-linking DNAs and DNA and proteins. Busulfan inhibits thioredoxin reductase activity. It also induces apoptosis. It is an immunosuppressive and myeloablative chemotherapeutic agent.Busulfan (NSC-750) can be used to induce animal models of Anemia.

Related Targets

Apoptosis related DNA alkylator