Preemptive Bone Marrow Transplantation and Event-Free Survival in Fanconi Anemia

- Preemptive bone marrow transplantation would prevent leukemia in patients with Fanconi anemia
- A transplantation incurs risks of transplantation-related mortality and solid tumors
- A mathematical model (Markov) estimated the risks and benefits of transplantation
- Preemptive bone marrow transplantation has more benefit for younger patients
- This model may be useful for shared decision-making between families and physicians

Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome associated with high risks of severe bone marrow failure (BMF), acute myeloid leukemia (AML), and solid tumors (ST). Bone marrow transplantation (BMT) provides a theoretical cure for hematologic risks (BMF, AML), but it introduces uncertain risks of transplantation-related mortality (TRM) and carcinogenicity. We developed a mathematical (Markov) decision model to estimate event-free survival (EFS) conditional on age based on per-year cause-specific hazard rates. We assumed that preemptive (PE) BMT eliminates the risks of BMF and AML, but it may introduce independent risks of TRM or influence the trajectory to ST. Our model suggested that the expected mean EFS in FA is higher for PE-BMT at young ages, with minimal risk of TRM and with little carcinogenicity. PE-BMT in adults decreased expected EFS because of the greater competing risk of ST in adulthood. Estimates of EFS conditioned on attained age may be used in shared decision-making when clinicians must counsel patients using limited data. Our methods may be used to model early transplantation in other blood disorders for which hematopoietic stem cell transplantation mitigates some but not all of the risks.