Patients with myelofibrosis (MF) who were treated with fludarabine and busulfan, plus low-dose total body irradiation (TBI), had a significant reduction in graft failure compared to MF patients treated with fludarabine and busulfan alone, according to a retrospective review of patient data.
The authors, led by Craig W. Freyer, PharmD, of the Hospital of the University of Pennsylvania, reviewed data from adults with MF who underwent allogeneic hematopoietic cell transplant (allo-HCT) at a single center between 2008 and 2020 and received fludarabine and busulfan alone (n=8) or fludarabine and busulfan plus TBI (n=25). The results were published in Transplantation and Cellular Therapy.
The primary endpoint of the study was the incidence of graft failure, while secondary endpoints included time to engraftment, acute and chronic graft-versus-host disease (GVHD), hepatic sinusoidal obstruction syndrome (SOS), non-relapse mortality, as well as overall response rate, progression-free survival, and overall survival (OS).
Graft failure was significantly lower in patients who received fludarabine and busulfan plus TBI (4%) than in patients who received fludarabine and busulfan alone (50%; relative risk, 0.08; 95% CI, 0.01-0.62; P=.0016). All cases of graft failure in the fludarabine and busulfan group were secondary. The single case of graft failure in the fludarabine and busulfan plus TBI group was primary.
“Graft failure incidence was similar with related or unrelated donors and in patients who did and did not receive Janus-associated kinase inhibitors prior to allo-HCT,” the authors wrote.
Molecular remission and donor chimerism greater than 99% were significantly more common with fludarabine and busulfan plus TBI treatment than with fludarabine and busulfan alone, the authors reported.
Progression or relapse at 1 year was reported in 63% of patients treated with fludarabine and busulfan but was not reported in any patients treated with fludarabine and busulfan plus TBI (P<.001). However, the median OS was not significantly different between patients treated with fludarabine and busulfan plus TBI (49 months) and fludarabine and busulfan alone (30.8 months; hazard ratio, 0.98; 95% CI, 0.33-2.88; P=.97).
SOS was reported in 24% of patients who received fludarabine and busulfan plus TBI and in no patients who received fludarabine and busulfan alone, but the difference was not statistically significant. There were no significant differences in acute GVHD, chronic GVHD, or time to engraftment.
“[Fludarabine and busulfan plus] TBI resulted in a significant reduction in graft failure and significant improvement in the frequency of molecular remission and full donor chimerism compared to [fludarabine and busulfan],” the authors wrote. “The addition of low dose TBI to [fludarabine and busulfan] successfully mitigates against graft failure in patients with MF without increased rates of complication.”