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. 2001 Jun;54(6):428–434. doi: 10.1136/jcp.54.6.428

Status of umbilical cord blood transplantation in the year 2001

J Hows 1
PMCID: PMC1731437  PMID: 11376014

Abstract

Umbilical cord blood (UCB) transplantation is limited to small recipients because of the low haemopoietic cell dose. Children from ethnic minority groups may benefit most from cord blood transplantation. Cohort controlled retrospective data indicate that there is significantly less acute and chronic graft versus host disease associated with the transplantation of human major histocompatibility complex (HLA) identical sibling cord blood compared with HLA identical sibling marrow. Controlled data are not yet available to confirm this observation in unrelated donor cord blood transplantation. The difference in leukaemic relapse seen after cord blood compared with bone marrow transplantation is also unknown. Tentative recommendations for the use of umbilical cord blood for transplantation are as follows. Collection is indicated from healthy newborn siblings when urgent transplantation is required for an older child in a family. The haematologist responsible for the older child, with the approval of the family and the obstetric team, should contact the medical director of the nearest cord blood bank to discuss arrangements for the UCB to be collected and HLA typed. Antenatal blood sampling to HLA type the fetus is not recommended. Umbilical cord blood should be considered when allogeneic transplantation is the treatment of choice for a child who does not have an HLA identical sibling, or a well matched unrelated adult volunteer donor. The potential advantages and disadvantages of using an HLA haplotype matched peripheral blood stem cell family donor rather than an unrelated cord blood donation should be discussed. There are no comparative data available as yet. At present, UCB transplantation should only be considered if a suitably matched donation contains at least 2 x 107/kg nucleated cells. Effectively, this means that most adults and larger children are not suitable recipients.

Key Words: umbilical cord blood transplantation • graft versus host disease • bone marrow transplantation • leukaemia • cell expansion

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Figure 1 The relation between the infused CD34+ cell dose and (A) platelet and (B) neutrophil recovery after unrelated umbilical cord blood transplantation. The numbers within the graphs refer to the dose of CD34+ cells (x106/kg). There is a strong direct correlation between cell dose and peripheral blood recovery. Transplants containing less than 0.3 x 106/kg CD34+ cells have a high probability of poor engraftment or non-engraftment.

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Figure 2 The effect of CD34+ cell dose on survival after unrelated umbilical cord blood transplantation. (A) There is a direct correlation between increasing cell dose and the probability of survival at one year post transplant. Patients receiving less than 0.3 x 106/kg CD34+ cells have a significantly higher probability of death in the first year after transplantation than those receiving a higher CD34+ cell dose. The numbers within the graphs refer to the dose of CD34+ cells (x106/kg). (B) The relatively minor effect of human major histocompatibility complex (HLA) mismatch on survival compared with the major effect of cell dose. HLA typing was performed by intermediate resolution DNA methodology. mm, number of HLA loci mismatched.

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Figure 3 The proportion of recipients of different weight for whom an optimal cord blood donation (> 3.7 x 107/kg nucleated cells) or a just sufficient donation (> 2.0 x 107/kg) of nucleated blood cells is available in the Bristol cord blood bank. With the exception of when the potential recipient has a common HLA type, the chance of finding a large enough donation for an adult with two or less human major histocompatibility complex (HLA) mismatches using high resolution DNA typing is very low.

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Figure 4 Engraftment of human cord blood cells with or without in vitro expansion in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice after five weeks. Cord blood CD34+ cells were cultured in vitro for three, seven, or 10 days in stem cell factor (SCF), Flt3 ligand (Flt3), thrombopoietin (TPO), interleukin 3 (IL-3), IL-6, and granulocyte colony stimulating factor (G-CSF), all at 10 ng/ml. Seventy six mice received fresh or cultured cells from eight different cord bloods. (A) SRC are still present after three, seven, and 10 days of culture. The mean level of engraftment with cultured cells was lower than with fresh cells (1% v 7.4%) when the same number of expanded or fresh CD34+ cells was transplanted. This suggests that although engraftment of expanded cells occurs there is less efficient proliferation and differentiation in vivo, resulting in a lower proportion of human cells in the bone marrow after five weeks. (B) If the input number of expanded cells is reduced, engraftment is seen with the expanded progeny of only 0.6 x 104 CD34+ cells. This suggests that some expansion of SRC numbers may occur in vitro.

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