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Keywords: busulfan; cord blood transplantation; cyclophosphamide; fludarabine; hematopoietic cell transplantation; myeloablative conditioning EN busulfan cord blood transplantation cyclophosphamide fludarabine hematopoietic cell transplantation myeloablative conditioning 374 376 3 08/05/21 20210901 NES 210901 ACKNOWLEDGEMENTS The authors thank all of the physicians and staff at the hospital and the cord blood banks in Japan for their help in this study. This retrospective study included 31 adult patients who underwent unrelated single-unit CBT (SCBT) following a radiation-free myeloablative conditioning regimen, consisting of fludarabine added to full-dose busulfan and cyclophosphamide for the treatment of hematological malignancies at our hospital between 2002 and 2020. Radiation-free myeloablative conditioning consisting of fludarabine added to full-dose busulfan and cyclophosphamide in single-unit cord blood transplantation for adults. [Extracted from the article]

Abstract The optimal intensity of a conditioning regimen might be dependent on not only age and comorbidities but also disease activity and the type of graft source. We evaluated the outcome of unrelated single cord blood transplantation (CBT) using a conditioning regimen of fludarabine 180 mg/m2, i.v. busulfan 9.6 mg/kg, 4 Gy total body irradiation, granulocyte colony-stimulating factor–combined high-dose cytarabine (12 g/m2) in 23 elderly patients (median, 64 years) with nonremission myeloid malignancies between 2013 and 2018 in our institution. All but 1 patient achieved neutrophil engraftment at a median of 23.5 days (range, 18 to 50). With a median follow-up of 28 months, the probabilities of overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse at 2 years were 62%, 52%, and 26%, respectively. The cumulative incidences of nonrelapse mortality at 100 days and 2 years were 9% and 22%, respectively. In the univariable analysis a higher proportion of blasts in bone marrow and in peripheral blood and a monosomal or complex karyotype were significantly associated with inferior OS and DFS. Poor cytogenetics were significantly associated with inferior DFS and increased relapse incidence. These data demonstrate that this reduced-toxicity myeloablative conditioning regimen was tolerable and effective in terms of engraftment, relapse, and survival in single CBT for elderly patients with nonremission myeloid malignancies. Highlights • We designed a reduced-toxicity myeloablative conditioning regimen consisting of fludarabine 180 mg/m2, busulfan 9.6 mg/kg, 4 Gy TBI, and G-CSF–combined Ara-C for elderly patients with nonremission myeloid malignancies in single cord blood transplantation. • The cumulative incidence of neutrophil engraftment was 91% at day 42 after CBT. • The probabilities of overall survival, disease-free survival, and cumulative incidence of relapse at 2 years were 62%, 52%, and 26%, respectively. [ABSTRACT FROM AUTHOR]

Comparative studies between total body irradiation (TBI)-based and busulfan-based myeloablative conditioning (MAC) regimens for cord blood transplantation (CBT) have been limited. We retrospectively analyzed the results of single-unit CBT in 333 adult patients who received either TBI-based (n = 258) or busulfan-based (n = 75) MAC regimens at our institute. After adjusting for significant variables in the univariate analysis, there were no significant differences in neutrophil recovery (hazard ratio (HR), 0.88; p =.460), grade III–IV acute graft-versus-host disease (GVHD) (HR: 1.40, p =.410), extensive chronic GVHD (HR: 0.73, p =.380), relapse (HR: 0.61, p =.270), non-relapse mortality (HR: 1.38, p =.420), overall survival (HR: 1.18, p =.637), or event-free survival (HR: 1.08, p =.773), although platelet recovery was lower with marginal significance for the busulfan-based regimen (HR: 0.67, p =.068). In subgroup analysis, TBI-based regimens were superior to busulfan-based regimens in terms of survival for acute lymphoblastic leukemia, but not for myeloid malignancies. Further investigation is warranted even for CBT. [ABSTRACT FROM AUTHOR]

An intensified myeloablative conditioning regimen, involving the addition of granulocyte colony-stimulating factor (G-CSF)-combined high-dose cytarabine (12 g/m2) to standard total body irradiation and cyclophosphamide, has been performed for adult patients with myeloid malignancies in single-unit cord blood transplantation (CBT) since 1998 in our institute. We update the results of CBT, as the first allogeneic hematopoietic cell transplantation after this conditioning regimen, in 169 patients with a median long-term follow-up of 10.4 years. The median age was 43 years (range, 16 to 59 years). Ninety-four patients (56%) were in non-remission at the time of CBT, and 124 patients (73%) were acute myeloid leukemia. The median cryopreserved cord blood total nucleated cell dose and CD34+ cell dose was 2.40 × 107/kg and 0.93 × 105/kg, respectively. The cumulative incidence of neutrophil recovery at 42 days was 94.4% (95% confidence interval [CI]: 88.6–97.3%). Among the whole cohort, 105 patients were still alive at the end of the study period. The cumulative incidences of relapse and non-relapse mortality at 10 years were 26.0% (95% CI: 19.5–33.0%) and 16.9% (95% CI: 11.4–23.4%), respectively. There was an overall survival probability of 62.5% (95% CI: 54.3–69.7%) at 10 years. Higher disease risk index alone significantly affected higher overall mortality (hazard ratio 2.21, P = 0.003) in multivariate analysis. These outcomes demonstrate that G-CSF-combined myeloablative conditioning could have favorable long-term remission rates for adult patients with myeloid malignancies undergoing single-unit CBT. [ABSTRACT FROM AUTHOR]