Haematopoietic stem cell transplants
IN BRIEF - 13TH DECEMBER 2016
Dr Mike Potter, consultant haematologist at The London Clinic, explains the benefits and complexities of haematopoietic stem cell transplants.
Haematopoietic stem cells are organ-specific stem cells which occur in the blood and bone marrow systems. These stem cells produce two other types of cell: the first are myeloid progenitor cells, which go on to produce the cells needed for the blood system, such as red blood cells and platelets; the second are lymphoid progenitor cells which produce the cells used to build our immune system.
Embryonic stem cells, which people are more likely to have read about, are the super stem cells that are not organ-specific and can create any kind of cell—you start with one cell and end up with a baby. The use of embryonic stem cells has raised some real ethical questions because they are collected from foetuses, but haematopoietic stem cell work does not have these issues: the cells occur in the blood and bone marrow, so they are easy to collect from a donor.
Haematopoietic stem cells are used in two types of transplant: autologous and allogeneic. In autologous transplants, the stem cells come from the patient. In allogeneic transplants, they come from a donor.
We predominently use these transplants to enhance the treatment of patients with malignant diseases, such as lymphomas and myeloma. The idea is to help the patient’s immune system, allowing us to give stronger, more aggressive treatment.
With chemotherapy, the more we give, the better the response in terms of killing tumour cells, but we also kill bone marrow cells and this places a limit on the levels of chemotherapy we an apply: you can wipe out the bone marrow to such an extent that it cannot produce enough cells to maintain a viable immune system, leaving the patient vulnerable to serious infections. If you can raise that limit you can expose the patient to stronger chemotherapy and kill more cancer cells with each treatment, thereby increasing your chances of success.
Haematopoietic stem cell transplants
For an autologous transplant, we collect the stem cells from the patient before the chemotherapy, then freeze them. After the treatment, we re-introduce the cells we have collected. These then generate new, healthy myeloid and lymphoid progenitor cells, which start rebuilding the patient’s blood and immune systems. This helps fight the cancer, as well as protecting the patient from other diseases.
Allogeneic stem cell transplants are a little more complex. We will use a donor if the sick patient’s own immune system is struggling to kill the tumorous cells of a particular malignant disease such as leukaemia; the hope is that the healthy donor’s immune system will be more successful.
We also use allogeneic transplants to help with some specific conditions in which the patient’s blood or immune system has a fundamental congenital fault, and therefore is not performing properly. For example, thalassemia is a genetic condition where the patient does not make enough red cells. By introducing healthy haematopoietic stem cells from a donor, they build a new blood system which functions properly and produces the necessary amount of blood cells.
The way we now collect stem cells represents a real step forward and is one of the reasons the transplants are as successful as they are. We used to collect stem cells exclusively from bone marrow, which involved an operation under a general anaesthetic where we used needles to suck the liquid marrow out of the pelvis. It was painful for the patient afterwards and there was a limit to the amount we could collect during each operation.
Now, the person from whom we are collecting the cells is given a growth-stimulating drug designed to increase the production of the stem cells in the bone marrow. This is combined with a drug that breaks down a type of adhesion molecule in the marrow which holds on to the stem cells, thereby releasing the extra cells produced into the peripheral blood for us to collect.
Stem cells A class of undifferentiated cells that are able to differentiate into different specialised cell types.
Bone marrow The spongy tissue within the bones which is home to stem cells. Chemotherapy A type of cancer treatment which uses medication to kill cancer cells by damaging them so they can’t reproduce and spread.
Lymphoma A cancer of the lymphatic system, which has two forms: Hodgkin lymphoma and non-Hodgkin lymphoma.
Myeloma A cancer arising from plasma cells: a type of white blood cell made in the bone marrow.
We attach the patient to a machine by two needles. Through one, the blood flows out into a centrifuge-based system, which separates different cells in the blood based on their size. This separates and collects the stem cells, then the rest of blood is remixed before being returned to the patient through the second needle. It is a very safe procedure and takes one or two sessions to get all the stem cells we need. The great thing is that this is an outpatient technique which lasts a few hours, after which the patient can return home.
We can process the stem cells to try and enhance their function in certain ways: if it’s an autologous cell transplant, we might look to remove any tumour cells, or we can pick out T-cells, which are the immune active cells. We can then add them back to the patient later in their treatment to give the immune system a boost. In reality, though, we don’t often need to manipulate the cells before returning them to the patient.
Haematopoietic stem cells like being in the bone marrow and have homing receptors, so in a transplant all we have to do is re-introduce them to the blood stream—they then find their way back to the bone marrow and start to grow. The patient’s blood and immune systems will start to recover as they get to work.