Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival

Abstract

The potential benefits of unrelated donor marrow transplantation are offset by the immunologic complications of graft-versus-host disease (GVHD) and infection. Therefore, we used cryopreserved umbilical cord blood (UCB) as a strategy to reduce the risks of GVHD and treatment-related mortality (TRM) and improve survival. Data on 102 patients (median age 7.4 years) who received transplants between 1994 and 2001 for the treatment of malignant (n = 65; 68% were high-risk patients) and nonmalignant (n = 37) diseases were evaluated. Log-rank tests and Cox regression analyses were used to determine the effects of various demographic, graft-related, and treatment factors on engraftment, GVHD, TRM, relapse, and survival. As of October 15, 2001, the median follow-up was 2.7 years (range, 0.3-7.2). Incidences of neutrophil and platelet engraftment were 0.88 (CI, 0.81-0.95) and 0.65 (CI, 0.53-0.77), respectively. Notably, incidences of severe acute and chronic GVHD were 0.11 (CI, 0.05-0.17) and 0.10 (CI, 0.04-0.16), respectively. At 1 year after transplantation, proportions of TRM and survival were 0.30 (CI, 0.21-0.39) and 0.58 (CI, 0.48-0.68), respectively. In Cox regression analyses, CD34 cell dose was the one factor consistently identified as significantly associated with rate of engraftment, TRM, and survival. Despite the low incidence of GVHD, the proportion of patients with leukemia relapse at 2 years was 0.17 (CI, 0.00-0.38) and 0.45 (CI, 0.28-0.61) for patients with standard and high-risk disease, respectively. There is a high probability of survival in recipients of UCB grafts that are disparate in no more than 2 human leukocyte antigens (HLAs) when the grafts contain at least 1.7 × 105 CD34+ cells per kilogram of recipient's body weight. Therefore, graft selection should be based principally on CD34 cell dose when multiple UCB units exist with an HLA disparity of 2 or less.

Regulation of the embryonic erythropoietic niche: a future perspective

“…By combining these peptides with existing HSC culture protocol, we confirmed that KS-13 and modified-KS-13 increased the number of CD34 + /CD38 − HSCs over 50-fold within several days. Transplantation of higher numbers of CD34 + HSCs reportedly improves clinical outcomes [626364], and our results showed that peptides might provide new aspect to ameliorate current method for ex vivo HSC expansion.…”

Single- or double-unit UCBT following RIC in adults with AL: a report from Eurocord, the ALWP and the CTIWP of the EBMT

“…This is unfortunate given that cell dose is one of the main predictive factors for CBT outcomes [26–28]. Transplantation of two CB units has been introduced by investigators from the university of Minnesota to increase the cell dose infused [13, 29].…”

The effect of inter-unit HLA matching in double umbilical cord blood transplantation for acute leukemia

“…Data, mostly from the single UCB transplantation setting, support the use of donor specific anti-HLA antibodies, 16 high resolution HLA-matching, 17 matching at HLA-C, 18 CD34 + cell dose, 7,8,19,20 and cell viability 8 to refine UCB unit selection. However, these data are not always reproducible in the double UCB focused studies.…”