Reduced-Intensity Cord Blood Transplantation in Adult Patients for the Recurrence after Allogeneic Transplantation.

Backgrounds: For more than 10 years, umbilical cord blood has become an alternative stem cell source for the patients with hematological malignancies requiring allogeneic stem cell transplantation. Cord blood transplantation (CBT) can be performed more quickly than other stem cell transplantation, since cord blood units are preserved in the deep freeze and 1–3 HLA mismatched donors are acceptable. Considering these advantage, we examined the feasibility of cord blood transplantation using reduced-intensity regimens (RI-CBT) for adult relapsed patients after allogeneic tranplantation.

Patients/methods: We reviewed medical records of 26 patients who received RI-CBT at Toranomon Hospital between November 2003 and June 2006. Median age of the patients was 36 years (range, 20–66). Underlying diseases were acute leukemia (n=17), myelodysplastic syndrome (n=4) and lymphoma (n=5). The stem cell source of the first transplantation were bone marrow from sibling donor (n=2), bone marrow from unrelated (n=5) donor, peripheral blood stem cell from sibling donor (n=5) and unrelated cord blood (n=14). Conditioning regimens comprised fludarabine 125–180 mg/m² in several combination with melphalan 80–140 mg/m², Busulfan 8–16mg/kg and total body irradiation (TBI) (4–8 Gy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n=5) or tacrolimus (n=21). Median number of total nucleated cells and CD34+ cells was 2.56×10⁶ cells/kg (1.91–5.94), and 0.86×10⁵ cells/kg (0.57–1.77) respectively. HLA disparities were 5/6 (n=2), 4/6 (n=22), and 3/6 (n=2).

Results: Median observation period was 58 days (range, 32–380). Overall survival for 1 year was 15% and 16 patients were died of disease progression (n=5) and infection (n=11). The infection in 4 patients was considered to be caused by regimen related toxicity (RRT). No grade IV toxicities (NCI-CTC Ver.3.0) were observed. The duration between two transplantations was longer in surviving patients compared to dead patients (98 days (range, 39–2108) and 262 days (range, 95–901), respectively), although significant difference was not detected. The stage of the disease in the second transplantation, conditioning regimens and HLA disparities did not influence to the outcome.

Discussion: We demonstrated that RI-CBT could be an available and feasible treatment for the relapsed patients after stem cell transplantation. Moreover, the RRT is acceptable even in the patients with an advanced disease.