A study sought to determine the optimal dose of posttransplantation bendamustine (PTB) to prevent graft-versus-host disease (GVHD) in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation (HCT). The results of the prospective trial were published in Transplantation and Cellular Therapy.
Prior to transplant, all patients received myeloablative conditioning with fludarabine and oral busulfan. Patients received PTB in doses of 140 mg/m2 (n=7), 100 mg/m2 (n=10), and 70 mg/m2 (n=10) on days +3 and +4 after transplant. Twelve patients were given single-agent PTB and subsequent- combination with tacrolimus and mycophenolate mofetil. There were 22 patients with acute myeloid leukemia (AML) and five with acute lymphoblastic leukemia (ALL).
Primary and secondary refractory disease was identified in 41% and 59% of patients, respectively. Upon conditioning, the median blast count in the bone marrow was 18%. Transplantation characteristics included matched sibling (n=5), matched or mismatched unrelated (n=15), and haploidentical donors (n=7).
Overall, 93% of patients achieved engraftment, including 89% who attained complete remission (CR) and 63% without measurable residual disease. Unexpectedly, cytokine release syndrome (CRS) was observed in 70% of patients following PTB. Common clinical symptoms included high fever (67%), abnormal liver function tests (67%), pancreatitis (63%), skin vasculitis (56%), enterocolitis (48%), and inflammation of oral mucosa (37%). Human leukocyte antigen-mismatched donor was predictive of CRS.
Overall, 44% of patients developed classical acute GVHD. A correlation was observed between grade II to IV acute GVHD and grade 3 to 5 CRS. Among the 100-day survivors, patients were more likely to develop moderate and severe chronic GVHD following single-agent PTB than combination immunosuppression. Three-year overall and event-free survival was 28% and 29%, respectively. No patients relapsed after 100 days. The dose groups had no statistically significant differences, but the 100 mg/k2 group had higher rates of survival. The survival rate was also higher among patients with AML than ALL (35% vs 0%; P=0.0157).