Reduced-Intensity Conditioning Followed by Unrelated Umbilical Cord Blood Transplantation for Advanced Hematologic Malignancies: Rapid Engraftment in Bone Marrow

Abstract

Reduced-intensity (RI) conditioning followed by cord blood transplantation (CBT) is a new treatment modality, but failure to engraft is a major concern. We describe 12 patients with advanced hematologic malignancies who underwent RI conditioning and CBT with a conditioning regimen consisting of 200 mg/m(2) fludarabine (Flu), 50 mg/kg cyclophosphamide (CY), and 3 Gy total body irradiation (TBI). Cyclosporin A and/or methotrexate were used for graft-versus-host disease prophylaxis. Cord blood grafts were not mismatched for more than 2 serologically defined HLA alleles but were later found by high-resolution DNA typing to be mismatched for 2 to 4 alleles in most cases. Short tandem repeat analysis of bone marrow cells at day 14 showed complete donor chimerism in 6 of the patients and mixed chimerism in 5, indicating rapid engraftment in the bone marrow, whereas the remaining patient experienced graft rejection. Neutrophil recovery was achieved at a median of day 17 (range, days 11-24) in 10 of the 11 patients with marrow chimerism at day 14. Of these 10 patients, however, transplantation-related mortality within 100 days occurred in 4 patients who showed failed platelet recovery and a lack of durable engraftment. Overall survival and disease-free survival rates were 41.7% and 33.3%, respectively. These results show that CB mismatched at 2 to 4 HLA alleles and transplanted with the Flu/CY/3 Gy TBI regimen is able to engraft in the bone marrow as early as day 14.

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

“…The use of UCB as the unrelated graft source with RI HSCT for leukemia is a novel approach. Several studies [30][31][32] with other hematological malignancies are encouraging, but disease specific outcomes are inconclusive. Previous UCB studies [33] have shown slower hematopoietic recovery and increased chronic GVHD associated with cord blood transplantation for leukemia.…”

A novel reduced-intensity umbilical cord blood transplantation using a recombinant G-CSF combined with high-dose Ara-C for active myeloid malignancies

“…CBT performed after myeloablative or reduced-intensity preconditioning has contributed to advancing HSCT therapy for these patients and has been extensively investigated, including comparisons of conditioning regimens (Table 3). 3,14,15,26,[28][29][30][31][32][33][34][35][36][37] The reported engraftment rate is 53-93%, and the rate has been improving, possibly owing to the introduction of double-unit CBT. The reported frequency of grade II-IV acute GVHD is 20-44%; the 1-year OS ranges from 33 to 71%, and the TRM at 1 year ranges from 12 to 43%.…”

Cord Blood Transplantation in Adults with Acute Leukemia

“…Reduced-intensity conditioning (RIC) regimens have emerged as a novel transplantation modality for those patients with the expectation of reducing TRM and increasing survival after allogeneic HSCT. This strategy was recently expanded for quick use with stem cell sources not only from BM or mobilized PB, but also from CB (Barker et al, 2003;Miyakoshi et al, 2004;Chao et al, 2004;Misawa et al, 2006;Brunstein et al, 2007;Komatsu et al, 2007;Majhail et al, 2008;Uchida et al, 2008;Cutler & Ballen, 2009;Horwitz & Chao, 2010). Several studies have reported on CBT using RIC for adult patients with leukemia, and selected studies using mainly single CB unit are detailed in Table 4.…”