Umbilical Cord Blood Transplantation after Reduced-Intensity Conditioning for Elderly Patients with Hematologic Diseases

Abstract

Although allogeneic hematopoietic stem cell transplantation is a potentially curative approach for advanced hematologic diseases, its application to elderly people is limited because of their comorbid physical conditions and lower chance of finding suitable related donors. Umbilical cord blood transplantation with reduced-intensity pretransplant conditioning (RI-UCBT) is 1 way to avoid these obstacles. We analyzed elderly patients aged 55 years and older with hematologic diseases who underwent RI-UCBT at our institute to assess feasibility and effectiveness of this treatment approach. Among the 70 patients included, 50 died, 74% of them from nonrelapse causes. Infection was the primary cause of death. Estimated overall survival and progression-free survival at 2 years were both 23%. In multivariate analyses, standard-risk diseases, age younger than 61 years, grade 0-II acute graft-versus-host disease, and the absence of preengraftment immune reaction were significantly associated with better overall survival. RI-UCBT is a potentially curative and applicable approach for elderly patients. Higher mortality, especially from nonrelapse causes, is the biggest problem to be solved to increase the feasibility of this approach.

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

“…They subsequently reported the merit of the use of Tac instead of CsA to suppress post-CBT immune reactions, including pre-engraftment immune reaction and acute GVHD [82,83]. After demonstrating the feasibility of RIC CBT with CsA or Tac alone for patients aged 55 years and higher [84], Uchida et al [85] added MMF to Tac as GVHD prophylaxis in RIC CBT for elderly patients. They reported a significantly higher engraftment rate (90 vs. 69 %) and a lower incidence of pre-engraftment immune reaction (16 vs. 52 %) in the Tac and MMF group, but the incidences of acute and chronic GVHD were comparable between the two groups.…”

The great debate: haploidentical or cord blood transplant

“…Several investigators have analyzed the outcomes after a reduced-intensity regimen in an effort to offer potentially curative therapy without the high toxicity of a myeloablative regimen. Uchida et al 6 transplanted 70 patients over age 55 (median age 61) years with a variety of fludarabine-containing conditioning regimens. Progression-free survival at 2 years was 23%, with the majority of deaths from infection.…”

Future of cord blood for oncology uses

“…These older patients make up a large population of patients with hematological malignancies who would potentially benefit from RIC UCB transplantation strategies, and this is reflected in the growing number of publications in the area. [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] Outcomes after RIC UCB transplantation have been encouraging, with most patients achieving prompt neutrophil recovery and donor chimerism plus promising PFS and OS (Table 3). There is variability in the incidence of acute (10-60%) and chronic (10-40%) GVHD, which may be related to differences in the conditioning regimen, post transplantation immunosuppression, and the number of UCB units composing the graft and ethnic heterogeneity of the study population.…”