Low incidence of primary graft failure with bendamustine, fludarabine, and busulfan conditioning prior to haploidentical allogeneic hematopoietic cell transplantation

The outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) have improved with the implication of new in vivo and ex vivo graft-versus-host disease (GVHD) prophylaxis regimens. However, primary graft failure is still reported more frequently in haplo-HCT compared to a matched donor HCT. We conducted a pilot study (NCT04942730) to evaluate the impact of adding bendamustine to fludarabine and busulfan conditioning on engraftment after haplo-HCT. Bendamustine was administered on days -7 and -6 in the 130 mg/m2 dose. Fifty patients with malignant disorders in complete hematologic response were enrolled. The cumulative incidence of engraftment was 98% (95% confidence interval [CI] 77%-99%) with a median of 20 days. One-year overall survival was 67.9% (95% CI 53.2%-86.7%), event-free survival was 68.1% (95% CI 53.4%-86.8%), the cumulative incidence of relapse was 4.9% (95% CI 0.82%-15%), and nonrelapse mortality was 27% (95% CI 13%-44%). Relatively high incidence of viral reactivations (68%, 95% CI: 52%-79%) and invasive fungal infections (19%, 95% CI: 9.3%-32%) were observed. The study justifies further investigation of fludarabine, busulfan, and bendamustine conditioning in haplo-HCT.