Myelofibrosis Transplant Outcomes Improve with Busulfan, Fludarabine, and Thiotepa Conditioning

For people with myelofibrosis (MF), allogeneic stem cell transplant (allo-SCT) remains the only known curative treatment. While supportive care and symptom management have improved in recent years, relapse continues to be one of the leading causes of transplant failure and mortality.

A New Study To Improve Transplant Success

A recent large registry study examined a chemotherapy conditioning regimen that includes busulfan and fludarabine (BuFlu) with or without the addition of thiotepa, to improve transplant success rates for people with myelofibrosis.

The results were very positive:

• Median age of patients was 63 years old. 74 patients were studied.
• 43% remained disease-free for 2 years.
• Relapse rate was 41%.
• 53% of patients had myelofibrosis, and 47% had post-essential/post-polycythemia vera MF.
• 80% of patients had received ruxolitinib prior to their stem cell transplant.

When the intensity of the BuFlu treatment was decreased, outcomes were not as successful: 2 year disease-free survival was only 24% and relapse rate was 50%.

This study demonstrated that over a period of 3 weeks, busulfan was fractionated (a way of dividing a total dose of radiation or chemotherapy into separate doses that are larger or smaller than usual) which allowed for increased conditioning and the ability to introduce other medications (fludarabine) to the treatment profile. This improved efficacy and helped to manage side effects safely.

How the BuFlu + Thiotepa Regimen Works

This regimen involves fractionating busulfan over three weeks, meaning the total dose is divided into smaller portions to reduce toxicity while maintaining treatment strength. This approach also allows the safe addition of other agents, like fludarabine and thiotepa.

What is Thiotepa?

Thiotepa is a chemotherapy medication that supports engraftment (when the transplanted cells begin to grow and make healthy blood cells) and has anti-leukemia effects. Adding it to BuFlu can improve transplant outcomes by strengthening conditioning and reducing relapse.

80mg of busulfan was given outpatient, followed by 5mg of thiotepa and fludarabine at 30-40mg. All patients received cyclophosphamide after transplant, and preventive treatment for graft-versus-host disease (GVHD).

Primary Study Results

These outcomes represent one of the most successful sets of data for myelofibrosis transplant patients using matched donors and modern GVHD prevention strategies.

• There were no primary graft failures.
• The median time to neutrophil engraftment was 17 days.
• The median time to platelet engraftment was 28 days.
• 2 year overall survival was 72%.
• 2 year moderate to severe graft versus host disease was 13%

Conclusion

This is the largest completed study evaluating allo-SCT in MF patients using matched donors and a conditioning regimen of BuFlu plus thiotepa, followed by modern GVHD prophylaxis.

If you or your loved one is considering a stem cell transplant for myelofibrosis, this study offers encouraging news. The combination approach not only improved survival rates but also significantly lowered relapse risks, even in older patients and those pretreated with ruxolitinib.

Keep reading more articles like this and stay tuned for more updates in treatment advances, conferences and more! 

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Source: 

• Fractionated Busulfan, Fludarabine and Thiotepa Myeloablative Conditioning to Improve Transplant Outcomes for Myelofibrosis