Sources of Haematopoietic Stem Cells

There are potentially three main sources of haematopoietic stem cells for transplantation – bone marrow (BM), peripheral blood stem cells (PBSC) and umbilical cord blood stem cells.

 


Bone Marrow


Bone marrow (BM) is traditionally harvested from multiple well spaced sites on the iliac crests under general anaesthetic. Multiple aspirates are taken to obtain a transplantable size. The median number of nucleated cells collected is normally 2 x 108/kg patient weight. Collection usually aims for a minimum CD34+ count of 2 x 106/kg patient weight.

 

Bone Marrow (BM) is sourced from related donors or adult volunteers on registries. Registry searches and confirmation of donor type and medical clearance take time and so there is a lead up time (search time of 3 – 6 months) required when using BM compared to using cord blood for example. Bone marrow does however have the advantage of being able to return to the donor for future donor lymphocyte infusions. Bone marrow is collected under general anaesthetic and so although a safe procedure carries the same risks as any process that requires general anaesthetic. Bone marrow stem cells collected have a lower nucleated (median 2 x 108/kg patient weight) and CD34+ cell count (median 2 x 106/kg patient weight) than peripheral blood stem cells but much larger nucleated and CD34+ stem cells than cord blood stem cells. Engraftment with bone marrow haematopoietic stem cells is medium to fast, taking a median of around 21 days to neutrophil and platelet engraftment. BM transplantation carries a risk of causing GvHD and requires that patient and donor be well matched for HLA class I and II. BM transplantation carries a risk of transmitting infectious disease or acquired or congenital disorders if not uncovered as part of the donor work up.

 


PBSC


Peripheral blood stem cells are collected after being mobilised from the marrow with granulocyte colony stimulating factor (G-CSF). G-CSF is administered over several days prior to collection. The stem cells are collected by apheresis. The median number of nucleated cells collected is normally 9 x 108/kg patient weight. Collection usually aims for a minimum CD34+ count of 7 x 106/kg patient weight. One advantage of PBSC over BM is that the donor can return for further apheresis if the number of cells collected is not sufficient.

 

Peripheral blood stem cells (PBSC) are also sourced from related donors or adult volunteers on registries and have the same issues of long lead up time for donor work up as bone marrow. The donor is available for future collections for donor lymphocyte infusions. The collection process for peripheral blood is however easier and safer as it does not require general anaesthetic. G-CSF has not been shown to have any harmful short term effects though the long term effects are unknown. Total nucleated (median 9 x 108/kg patient weight) and CD34+ cell counts (median 7 x 106/kg patient weight) collected by PBSC are generally much higher than bone marrow collection. Engraftment with PBSC haematopoietic stem cells is faster than with bone marrow, taking a median of around 15 days to neutrophil and platelet engraftment. PBSC carries a risk of causing GvHD and requires that patient and donor be well matched for HLA class I and II. PBSC, like BM, also carries a risk of transmitting infectious disease or acquired or congenital disorders if not uncovered as part of the donor work up.

 


Cord Blood


Umbilical cord blood stem cells are collected post partum either in utero in the delivery room during the third stage of labour before the placenta is delivered or outside the delivery room ex utero from the freshly delivered placenta. In general, the in utero collection method yields a larger volume and higher total nucleated cell count, though more recent studies have shown that with appropriate training it is possible to obtain high collection volumes and cell counts ex utero. Cord blood can be sourced from cord blood banks either in single or double doses.

 

Cord blood stem cells have the advantage of being immediately available. Collection is easy and harmless. A disadvantage is that the donor is not available for further collection should a donor lymphocyte infusion be required to rescue the patient from a failing graft. Total nucleated (median 0.3 x 108/kg patient weight) and CD34+ cell counts (median 0.2 x 106/kg patient weight) are much lower than those obtained from BM or PBSC collection. For this reason cord blood was initially used predominantly for children. Use of double dose cord blood has increased the usage in adults. Cord blood has a lower risk of transmitting infectious diseases compared to BM and PBSC but the risk of transmitting congenital disorders is unknown. Engraftment with cord blood haematopoietic stem cells is slower than with either BM or PBSC, taking up to 35 days to neutrophil engraftment and platelet engraftment can take even longer. Transplantation with Cord Blood derived stem cells does lead to a reduced incidence and severity of GvHD due to the relative immaturity of the immune system at birth. This allows less stringent HLA matching criteria for cord blood transplantation with one or two HLA gene mismatches (i.e. 4/6 or 5/6 HLA-A, B, DRB1 mismatches) tolerated. Cell dose may be the more important factor for cord blood transplantation. An emerging consensus is to use cord with no more than 2 mismatches at HLA-A, B and DRB1 (4/6) provided cell dose is greater than 3 x 107/Kg of patient weight.

 

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