# Prospective, Randomized, Comparative Study of Myeloablative Fludarabine/Busulfan and Fludarabine/Busulfan/Total Body Irradiation Conditioning in Myeloid Diseases

## TL;DR

This study compared two treatment regimens for myeloid diseases and found that adding radiation reduced relapse risk but did not improve overall survival due to higher mortality.

## Contribution

A prospective, randomized trial evaluating the impact of adding total body irradiation to a standard conditioning regimen in myeloid disease patients.

## Key findings

- Relapse risk was numerically lower with Flu/Bu4/TBI but not statistically significant.
- Non-relapse mortality was higher in the Flu/Bu4/TBI group.
- Overall survival was similar between the two treatment arms at one year.

## Abstract

Allogeneic hematopoietic stem cell transplantation can cure myeloid diseases, such as acute myeloid leukemia (AML), but relapse after transplant can be fatal. Myeloablative conditioning regimens, such as fludarabine/busulfan (Flu/Bu), can help reduce the risk of relapse. Previous retrospective studies have shown that adding total body irradiation (TBI) to conditioning with Flu/Bu in acute leukemia can help reduce recurrence. This prospective, randomized study sought to confirm these findings by comparing two conditioning regimens—sequential 4-day regimen of Flu/Bu (Flu/Bu4) versus Flu/Bu4 and total body irradiation (400 cGy)—in patients with myeloid diseases, ~75% of whom had AML. In the AML cohort and holistic study population, risk of relapse was lower with Flu/Bu4/TBI than Flu/Bu4 but this was not statistically significant. Non-relapse mortality was increased in the Flu/Bu4/TBI arm. Consequently, overall survival at 1 year was similar between both treatment arms, meaning no survival advantage was observed with adding TBI to Flu/Bu4.

Background/Objectives: Allogeneic hematopoietic stem cell transplantation (alloSCT) is a curative treatment for myeloid diseases, yet relapse remains the major cause of post-transplant mortality. To reduce the risk of recurrence, we evaluated the addition of 400 cGy total body irradiation (TBI) to conditioning with fludarabine-busulfan (Flu/Bu4). Methods: In this prospective study, 46 patients with myeloid diseases were randomized to Flu/Bu4 or Flu/Bu4/TBI conditioning group. The Flu/Bu4 conditioning regimen consisted of fludarabine 40 mg/m2 on days -6 to -3 followed by busulfan 130 mg/m2 on days -6 to -3. Flu/Bu4/TBI conditioning regimen added 400 cGy TBI on day -1 to the FluBu4 regimen. Results: Among 34 acute myeloid leukemia (AML) patients, relapse was numerically lower in those who received Flu/Bu4/TBI (25%) versus Flu/Bu4 (44.4%) at three years (HR = 0.58, 95% CI 0.19 to 1.81, p = 0.35). Flu/Bu4/TBI appeared to increase the risk of non-relapse mortality (NRM) vs. Flu/Bu4 in AML patients at three years (25.0% versus 11.1%; HR = 2.11, 95% CI 0.51 to 8.83, p = 0.65). Overall survival (OS) was similar in AML patients undergoing conditioning with Flu/Bu4 (72.2%) versus Flu/Bu4/TBI (62.5%) at one year (p = 0.4). Conclusions: In conclusion, the addition of 400 cGy TBI to Flu/Bu4 reduced the risk of relapse but did not improve OS as a consequence of higher regimen-related mortality. Clinicaltrials.gov identifier: NCT01366612.