Prospective Cohort Study Comparing Intravenous Busulfan Versus Total Body Irradiation in Cord Blood Transplantation

Intravenous busulfan (IV-Bu) or total body irradiation (TBI) based regimens are currently the most widely used myeloablative conditioning regimens for patients with hematologic malignancies undergoing allogeneic stem-cell transplantation(allo-SCT). Numerous trials have been undertaken on the clinical outcomes between IV Bu and TBI, but there are no comparative data for cord blood transplantation(CBT). We conducted a prospective registry-based study to analysis the outcomes of IV Bu and TBI in CBT patients with hematologic malignancies.

From May 1, 2008 to Mar 31, 2016, a total of 331 consecutive patients with hematologic malignancies recieved singe unrelated CBT were involved in the study. Eligibility criteria for this analysis included:(1)Weigh ≧35 kilograms and age ≦ 60 years; (2)All patients recieved a single unit CBT but not a double units CBT; (3)Consensus criteria preparative regimens were based on full dose IV Bu(total 12.8 mg/kg, 0.8mg/kg every 6 h for 4 days) or TBI(total 12 Gy, 4 fractions) combined with Cy(60mg/kg × 2d); (4)GVHD prophylaxis regimens include cyclosporine(CSA) and mycophenolate mofetil(MMF) without Antithymocyte Globulin(ATG). Patients who has recieved a previous autologous or allogeneic transplantation was excluded in the study. The cumulative incidence of neutrophil engraftment were 91.6% in IV Bu/Cy cohort and 98.0% in Cy/TBI cohort(P < .001), respectively. The median follow-up time in IV Bu/Cy and Cy/TBI cohorts was 28.7(range, 12.2 to 91.3) months and 55.5(range, 13.1 to 117.1) months, respectively(P<.001). Of them, 200 patients received Cy/TBI, and 131 patients received IV Bu/Cy. The median dose of infused total nucleated cells were 4.51(range, 2.19 to 12.06 )× 10⁷/kg and 3.77(range, 2.14 to 9.05)(P < .001), respectively. And the median number of CD34+ cells was 2.61(range, 0.91 to 9.64) ×10⁵/kg and 2.01(range, 1.12 to 8.71)(P < .001), respectively. The median times to neutrophil engraftment were 16 days and 19 days(P < .001). The estimated DFS at 3 years were not statistically different between the conditioning regimens in univariate analysis. 63.9%±4.21% in patients undergoing conditioning with IV Bu/Cy and 54.4%±3.57% in patients undergoing conditioning with Cy/TBI(P = .21).These results were similar in multivariable analysis (HR, 1.03; 95% CI, 0.68 to 1.54; P = .905). Univariate analysis and multivariable analysis demonstrated that estimated OS and GRFS at 3 years were also not different between those two conditioning regimens.

Our resluts demonstrates that, compared with TBI, IV Bu regimen was associated with a higher incidence of graft rejection in CBT. But there was no difference in survival with no increased risk for NRM or relapse between two regimens. For those centers lack of radiation facilities, IV Bu may be a valid and efficient alternative to TBI. With the restriction of a retrospective registry analysis and limited patient munbers, rigorously designed prospective randomized controlled trials are needed to further investigated the availability of IV Bu and TBI for CBT.