Reduced-Toxicity Myeloablative Conditioning Consisting of Fludarabine/Busulfan/Low-Dose Total Body Irradiation/Granulocyte Colony-Stimulating Factor–Combined Cytarabine in Single Cord Blood Transplantation for Elderly Patients with Nonremission Myeloid Malignancies

Abstract

A B S T R A C TThe 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/m 2 , i.v. busulfan 9.6 mg/kg, 4 Gy total body irradiation, granulocyte colony-stimulating factorÀcombined high-dose cytarabine (12 g/m 2 ) 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.

Development of Pre-Engraftment Syndrome, but Not Acute Graft-versus-Host Disease, Reduces Relapse Rate of Acute Myelogenous Leukemia after Single Cord Blood Transplantation

“…The reduced-intensity MAC regimen included 4 Gy total body irradiation, i.v. busulfan 9.6 mg/kg, fludarabine 180 mg/m 2 , and cytosine arabinoside 12 g/m 2 with granulocyte colony-stimulating factor for patients age 60 years and those with comorbidities [33]. No patients received antithymocyte globulin or alemtuzumab as a conditioning regimen or GVHD prophylaxis.…”

Clinical outcomes of persistent colonization with multidrug-resistant Gram-negative rods in adult patients undergoing single cord blood transplantation

“…Median time to neutrophil engraftment after CBT is approximately one week longer than after allogeneic HCT from bone marrow or mobilized peripheral blood stem cells [5,6]. In addition, in our cohort, almost all patients received a TBIbased relatively high-intensity conditioning regimen prior to CBT [24][25][26], and the majority of patients received methotrexate-based GVHD prophylaxis, which could contribute to severe mucosal injury, such as oral mucositis and diarrhea. Therefore, prolonged neutropenia and mucosal injuries could lead to gut translocation of bacteria, which might have been a more important cause of bacterial infections including BSI, especially in CBT recipients in our study.…”

Prognostic impacts of peripheral blood erythroblasts after single‐unit cord blood transplantation

“…ABO compatibility status between CB unit and recipient was as follows: 77 match (27%), 80 minor mismatch (28%), 76 major mismatch (31%), and 45 bidirectional mismatch (14%). Conditioning intensity and GVHD prophylaxis are also shown in Table 1 26‐28 …”