MDS-4 Impact of pre-transplant cytoreductive treatment on high-risk MDS patients undergoing allo-HSCT

Challenge

Although allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only potential curative therapy for high-risk myelodysplastic syndromes (MDS), just a small percentage of patients receive a transplant. A pre-transplant cytoreductive treatment could improve a patient’s chances of achieving transplant but this therapy option is controversial. On the one hand, it could reduce disease burden prior to transplant and serve as a bridge until an HLA-compatible donor is found, yet on the other hand, it could increase transplant-related toxicity and early mortality. Furthermore, which pre-transplant treatment should be chosen (AML-like chemotherapy (CTX) versus hypomethylating agents (HMA)) remains unclear. 

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Project Partnership

• University of Navarra, Spain
• Salamanca University Hospital, Spain

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Project Leadership

• Ana Alfonso Piérola, University of Navarra, Spain
• Sofía Huerga Dominguez, University of Navarra, Spain
• María Diez-Campelo, Salamanca University Hospital, Spain

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Impact 

• Knowing which patients could benefit from pre-transplant cytoreductive therapy would facilitate clinical decision-making.
• Identifying prognostic factors that might influence the outcome could support the choice of treatment.
• Optimizing cytoreductive therapy might increase the chances of patients achieving allo-HSCT and improve their subsequent overall and progression-free survival. 

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Project Summary

Pre-transplant cytoreductive treatment of high-risk MDS patients could improve their chances of achieving a transplant. However, it is unclear which patients might benefit from this or which treatment option should be chosen. Therefore, this study aims to identify which high-risk MDS patients could benefit from pre-transplant cytoreductive treatment, which treatment option gives the most favorable outcome, and whether there are prognostic factors that might influence the therapy chosen.

This large, observational, retrospective, and multicenter study will include patients from the HARMONY database who are <75 years old, classified as high-risk MDS (IPSS-R score >3), and have received allo-HSCT. The size of this cohort is not yet known. For the comparison of pre-transplant therapy, the patients will be allocated into three groups: “HMA”, “CTX”, and “upfront” (patients who did not receive any therapy for MDS except for transfusions, growth factors, or a short course of hydroxyurea). Primary endpoints will be OS and PFS, and a range of prognostic variables will be analyzed. The overall objectives are: 

• Determine the percentage of high-risk MDS patients who receive a transplant. 
• Understand the impact of pre-transplant cytoreductive treatment on post-transplant outcomes in high-risk MDS patients undergoing allo-HSCT. 
• Investigate differences in OS and PFS between high-risk MDS patients receiving pre-transplant cytoreductive treatment and those who do not. 
• Compare OS and PFS between high-risk MDS patients receiving pre-transplant treatment with AML-like chemotherapy and hypomethylating agents. 
• Identify prognostic factors, such as adverse cytogenetics or elevated bone marrow blast counts, which may influence the type of cytoreductive therapy. 

Due to its size, this study should provide greater clarity about which high-risk MDS patients could benefit from pre-transplant cytoreductive therapy before they undergo allo-HSCT. It could also help clinicians decide which pre-transplant therapy a patient should receive based on their prognostic factors. These outcomes will hopefully improve the management of high-risk MDS and increase patient survival.
 

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