Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease

Abstract

To reduce the morbidity and mortality associated with unrelated donor bone marrow (BM) transplantation and potentially extend the pool of suitable donors, cryopreserved unrelated donor umbilical cord blood was considered as an alternate source of hematopoietic stem cells for transplantation. Patients with leukemia, BM failure syndrome, or inborn error of metabolism were eligible for a phase I clinical trial designed to estimate the risk of graft failure and severe acute graft-versus- host disease after transplantation of umbilical cord blood from unrelated donors. As of December 21, 1995, unrelated donor umbilical cord blood was used to reconstitute hematopoiesis in eighteen patients aged 0.1 to 21.3 years weighing 3.3 to 78.8 kg with acquired or congenital lympho-hematopoietic disorders or metabolic disease. Patients received either HLA-matched (n = 7) or HLA-1 to 3 antigen disparate (n = 11) grafts collected and evaluated by the New York Blood Center (New York, NY). The probability of engraftment after unrelated donor umbilical cord blood transplantation was 100% with no patient having late graft failure to date. The probability of grade III-IV acute graft-versus-host disease at 100 days was 11%. With a median follow-up of 6 months (range, 1.6 to 17 months); the probability of survival at 6 months is 65% in this high risk patient population. We conclude that cryopreserved umbilical cord blood from HLA-matched and mismatched unrelated donors is a sufficient source of transplantable hematopoietic stem cells with high probability of donor derived engraftment and low risk of refractory severe acute graft-versus-host disease. Limitations with regard to recipient size and degree of donor HLA disparity remain to be determined.

Placing the newborn on the maternal abdomen increases the volume of umbilical cord blood collected

“…Cord blood stem cell transplantation may be used in a wide range of haematological diseases (Wagner, 1994). Cord blood stem cells show self-renewal capacity, differentiate Newborn position and cord blood collection into all haematopoietic lineages, and are associated with a low incidence of graft vs. host disease, while retaining graft vs. leukaemia activity (Wagner et al, 1996). Foetal blood is rich in long-term repopulating haematopoietic progenitors, as evidenced by 562 successful foetal cord blood transplantations after chemotherapy .…”

“…Recent studies indicate that umbilical cord blood can be given to fully or partially histocompatibility leucocyte antigens (HLA)-matched siblings or to nonfamilial recipients for bone marrow reconstitution in genetic disorders and malignancies . When compared to adult peripheral blood, umbilical cord blood shows decreased immune responses to alloantigens, with a reported low incidence of graft vs. host disease, but with signi®cant graft vs. leukaemia activity (Wagner et al, 1996;David et al, 1997). However, a unit of placental blood collected from a single donor contains a relatively low number of CD34+ cells after processing and testing.…”

Impact of obstetric factors on cord blood donation for transplantation

“…Further research is required to optimize cell dose for larger recipients. Current investigations focus on in-vitro expansion of CB haemopoietic cells (Denning-Kendall et al, 1998) and pooling of CB donations (Shen et al, 1994;Weinreb et al, 1998).…”

Flt3L induces the ex‐vivo amplification of umbilical cord blood committed progenitors and early stem cells in short‐term cultures

“…Some investigators have observed an impaired long-term engraftment in mice transplanted with cells ampli®ed with IL-3 (Peters et al, 1996;Yonemura et al, 1997). In order to assess whether the early stem cell pool was preserved in short-term culture in the presence of GM-CSF/IL-3 fusion protein, we performed several tests to detect the more primitive stem cells in ex vivo generated cells.…”