Engraftment of Double Cord Blood Transplantation after Nonmyeloablative Conditioning with Escalated Total Body Irradiation Dosing to Facilitate Engraftment in Immunocompetent Patients

Abstract

To improve accrual to a randomized clinical trial of double unrelated cord blood (dUCB) versus HLA-haploidentical bone marrow (haplo-BM) transplantation, patients with less previous therapy and potentially greater immunocompetence were enrolled. To reduce the risk of graft rejection, patients randomized to receive dUCB received a higher dose of total body irradiation (TBI) (300 cGy versus 200 cGy). In this study, we investigated whether the inclusion of recipients of 300 cGy TBI influenced the trial outcomes. This was a secondary analysis of dUCB recipients, 161 who received TBI 200 cGy and 18 who received TBI 300 cGy. Fine and Gray regression was used to evaluate the effect of TBI dose on relapse and nonrelapse mortality (NRM). Cox regression was used for evaluation of neutrophil engraftment and overall survival. Patient characteristics were similar in the 2 TBI dose subgroups. The probability of neutrophil engraftment was 100% for patients who received TBI 300 cGy versus 91% (95% confidence interval, 86% to 95%) for those who received TBI 200 cGy (P = .64), which was similar after regression analysis adjusting for age, total infused nucleated cell dose, HLA matching to the patient, and comorbidity score. We also investigated whether the lower survival probability and higher cumulative incidence of NRM observed in the dUCB arm of BMT CTN 1101 could be influenced by the TBI 300 cGy patient subset. There was no significant difference in the 1-year incidences of NRM and relapse or in 1-year survival, even after adjustment in multivariate analysis. Patients in BMT CTN 1101 who received TBI 300 cGy and 200 cGy had similar engraftment and early mortality. We conclude that inclusion of a modified regimen for dUCB transplantation had no demonstrable influence on this large randomized trial.

Trial registration: ClinicalTrials.gov NCT01597778.

Keywords: Cord blood transplantation; Nonmyeloablative conditioning regimen; Total body irradiation.

Copyright © 2021. Published by Elsevier Inc.

Figures

Figure 1.

The figure shows the cumulative incidence of neutrophil engraftment at day +42 after dUCB for patients who received TBI 300 cGy (▪▪▪▪▪) and TBI 200 cGy (—).

Figure 2.

Regression analyses of the effect of the TBI dose on neutrophil engraftment and early mortality. The other variables adjusted for in the multivariate models were: Neutrophil Engraftment - HLA matching 6/6 HR 1.0, 5/6 HR 0.5 (95%CI 0.3-0.9), 4/6 HR 0.6 (95%CI, 0.3-1.1); HCT-CI score zero HR 1.0, HCT-CI score 1-2 HR 0.8 (95%CI, 0.6-1.3), HCT-CI ≥3 HR 1.0 (95%CI, 07-1.5), Age by decade HR 0.90 (95%CI, 0.79-1.03), TNC (log) HR 0.82 (95%CI, 0.67-1.01); Relapse HCT-CI score zero HR 1.0, HCT-CI score 1-2 HR 0.4 (95%CI,0.2-0.7, p<0.01), HCT-CI ≥3 HR 0.5 (95%CI, 03-0.9), Age by decade HR 0.89 (95%CI, 0.7-1.1), Disease Risk Index (DRI) low HR 1.0, Intermediate HR 2.0 (95%CI, 0.9-4.9), high HR 2.4 (95%CI, 2.4-6.3); Non-Relapse Mortality HCT-CI score zero HR 1.0, HCT-CI score 1-2 HR 2.1 (95%CI,0.8-5.6), HCT-CI ≥3 HR 1.7 (95%CI, 0.6-4.4), Age by decade HR 1.55 (95%CI, 1.06-2.24); Overall mortatlity HCT-CI score zero HR 1.0, HCT-CI score 1-2 HR 1.2 (95%CI, 0.7-2.4), HCT-CI ≥3 HR 1.2 (95%CI, 0.6-2.1), Age by decade HR 1.19 (95%CI, 0.9-1.5), DRI low HR 1.0, Intermediate HR 2.3 (95%CI, 0.9-5.9), high HR 2.1 (95%CI, 0.7-6.0).