Introduction
The haematopoietic stem cell transplant service (HSCT) (historically called the bone marrow transplant service) provides a definitive treatment for children and young people with a range of clinical conditions.
The overall service consists of:
- world-renowned consultants with decades of experience of HSCT in children and young people
- a specialist nursing team dedicated to the care of children and young people undergoing HSCT
- Allied Health Professionals such as dietetics, physiotherapy, occupational therapists, speech and language therapists
- psychologists, including a neuro-psychologist
- specialised and therapeutic play therapists
- administrative and managerial support
The service has strong working relationships with the paediatric critical care unit, paediatric paediatric anaesthetics and theatres, the Willink metabolic unit and many more.
The majority of care for patients undergoing HSCT is provided on ward 79, a unit dedicated to provide holistic care in a single place.
What is HSCT?
HSCT stands for haematopoietic stem cell transplant. It is a treatment that is expanding in use for an increasing list of conditions.
In this section, we give you an overview of the general principles of this treatment. In later sections we provide more information on conditions we treat at Manchester.
Meaning
First, let’s understand what each of the words mean.
The human body grows from a fertilised egg, which is a single cell. As the egg divides into increasing numbers of cells, we grow into babies and eventually adults. Over this time, our cells mature and specialise to undertake specific duties. Some cells specialise into red blood cells, to carry oxygen around the body, and others turn into skin, bone, and other organs. A stem cell is a cell that is able to produce cells of various different specialist functions.
A stem cell might be classified as haematopoietic. This means the stem cell is able to make blood cells but not any other type of cell. Interestingly, haematopoietic is a word that can be broken into two parts: haem means ‘of the blood’ and poietic means ‘producing’. So a haematopoietic stem cell is a cell that goes on to produce only blood cells of many types.
Transplants are treatments whereby materials are transferred from one person (the donor) to another (the recipient). This might be a whole organ (like a liver) or smaller elements like cells. Sometimes the donor and the recipient are unrelated, related (eg. a parent or sibling). Sometimes the donor and recipient are the same person – and this happens under special circumstances. If the transplant is between different people, it is called an allogeneic transplant. If the materials are given back to the original donor, this is an autologous transplant.
So when we say a haematopoietic stem cell transplant we are talking about treatments that transfer cells which are able to produce new blood cells in the recipient. The cells collected are typically of three main types: from the blood of veins/arteries (peripheral blood), from the bone marrow, or from blood of the umbilical cord.
The transplant process
There are many stages to transplants, and each patient’s care will be personalised to their needs. This section gives an overview of the common steps of the pathway – click on each header to read more.
The whole HSCT process spans many weeks and sometimes months. It is a complex process, with various medicines and procedures taking place, each with their own risks. However, HSCT offers the potential for a significant improvement to the life of children and young people in otherwise fatal conditions.
Assessment
Each patient will undergo assessments with the aim to determine the exact cause of their disease, the severity of the disease and its impact on the life of the individual and wider family and determine potential treatment options. If HSCT is agreed as the intended course of treatment the patient may undergo further tests with the aim to assess eligibility for the treatment. It is also important to take some measurements before treatment starts so they can be monitored during and after treatment to ensure that the treatment has been effective and well tolerated.
Mobilisation
Naturally the body has a general circulation of stem cells in order to carry out replacements and repairs that are normal in keeping you fit and healthy. However they can be hard to collect because they are dilute and spread across the whole body. During the ‘mobilisation’ stage doctors can prescribe a medicine that increases the number of stem cells in the body. The specific medicine will depend on the type of stem cells to be collected and the donor’s unique presentation. Each medicine may also have side effects. Most often the medicine is given via a regular injection over a number of days. The ‘mobilisation’ of stem cells makes collecting them much easier and quicker.
Collection
The ‘collection’ stage is when the cells are harvested. You might here the collected materials referred to as ‘source material’.
Most commonly peripheral blood is collected, but only specific stem cells are needed. A process called apheresis is used. During apheresis the patient has two lines inserted into their veins. One line takes blood from the body and into a specialised machine. The machine safely spins the blood, which has the effect to separate it into different parts. The stem cells are collected and pumped into a collection bag. The rest of the blood is given back to the patient.
The donor undergoes apheresis collection for a few hours each day, for 2-3 days. This allows for the collection of enough of the right type of cells. Every day, the collected cells are analysed by specialised laboratories on site. We look at the collected material to ensure the right cells have been collected, that they are healthy, and there are enough overall.
Modification
Some HSCT treatments involve a stage of genetic modification. See the section ‘treatment types’ for a detailed overview. Here we offer a short summary.
During the modification stage, the collected cells (called source materials) are packaged very carefully and dispatched to a specialist lab. The specialist lab then uses a variety of techniques to add a highly efficient new gene to the cell. This new gene provides the cell with an ability it was previously lacking but is essential to normal growth/development and a long life.
The lab then completes a range of checks to ensure the modification has been successful, only the intended modification has ben made and no others, the cells are healthy, and there are no contaminants. If all these stringent checks are completed the cells are carefully packaged and released (sent back) to the hospital.
Conditioning
Before a patient receives the new cells its necessary to reduce the amount of their original stem cells. This is because the original stem cells will interfere with the new cells. In some cases the recipient has full intensity conditioning to remove all existing stem cells – this is often the case in younger children who can tolerate the process. In others, only some of the patients stem cells are cleared.
During conditioning, the recipient is given a medicine and may have radiotherapy. The medicine is often given by injection over a few days, week or more. Regular blood tests are taken to monitor how many cells are depleted. While the conditioning period is underway the patient’s immune system is significantly impaired. For this reason the patient stays in hospital, in a room with additional measures to control infection. Once conditioning is complete, the patient moves quickly to the next stage.
Treatment
This is when the actual transplant takes place. The new cells are held in a bag of liquid and flow into the patient’s blood over a period of time (normally around one hour) through a line.
During the infusion the nursing team will make lots of observations to ensure the patient is safe and tolerating the new cells. After a few days of observation and assuming there are no complications, the patient may return to their local hospital or home.
Aftercare
Each patient will continue to have care provided from the transplant team for a few weeks or months following the transplant. This might mean attending the hospital, or we may simply discuss your blood tests results with a local care team to save families travelling more than needed.
After the transplant, the new cells settle into their new home. As they do this over a period of time, complications can arise (see later section). The transplant team have significant experience managing these complications and will provide support to reduce side effects.
A number of tests are also undertaken to determine how many of the new cells have settled, and how many of the old cells remain. Other tests calculate how well the new cells are functioning as expected. If there are a large proportion of new cells working efficiently we call this a successful engraftment. Engraftment may take a number of weeks or months to complete in full. Engraftment can also be partial, or fail completely.
Patients whose original disease requires ongoing monitoring will continue to receive care from their local hospital/original consultant.
Treatments we offer
There are a variety of HSCT treatments, each highly targeted to specific conditions.
Kymriah (tisagenlecleucel) is a type of CAR-T therapy
CAR-T stand for ‘Chimeric antigen receptor T-cell’ and Kymriah is one of a number of CAR-T therapies available.
Kymriah is a medicine for treating the following types of blood cancer:
• B-cell acute lymphoblastic leukaemia (ALL), in children and young adults up to 25 years of age whose cancer did not respond to previous treatment, has come back two or more times, or has come back after a transplant of stem cells;
• Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in adults whose cancer has come back or did not respond after two or more previous treatments.
Kymriah is a type of advanced therapy medicine called a ‘gene therapy product’. This is a type of medicine that works by delivering genes into the body.
Libmeldy (atidarsagene autotemcel)
Libmeldy (atidarsagene autotemcel) is a medicine used to treat children with metachromatic leukodystrophy (MLD). MLD is a rare inherited disorder in which there is a change (mutation) in a gene needed to make an enzyme called arylsulfatase A (ARSA), which breaks down substances called sulfatides. As a result, sulfatides build up and damage the nervous system and other organs, causing symptoms such as walking difficulties, gradual mental deterioration and eventual death.
Libmeldy is used in children with MLD who have mutations in the ARSA gene. It is given to
- those with late infantile or early juvenile forms of the disease who have not yet developed symptoms;
- those with early juvenile MLD who have initial symptoms but can still walk independently and have not yet developed mental deterioration.
There are a variety of eligibility criteria that a joint team of specialists in MLD, HSCT and neurology will assess for each individual patient.
Our team
The team at the HSCT service is highly experienced.
Our facilities
Our facilities cater to a very broad range of children and young people undergoing HSCT, and their wider families during a long stay. These include:
- A single, dedicated HSCT unit (ward 79) with a mix of single occupancy rooms and 4-bedded bays
- Two overnight rooms for parents/carers adjacent to the ward, meaning one parent/carer is only a short walk away
Families travelling from beyond Greater Manchester or who may struggle with travel for repeat visits may also find accommodation available at Ronald McDonald House. Ronald McDonald House is a charitable organisation offering a free ‘home away from home’ accommodation. It has 65 en-suite bedrooms, a family day room, cooking facilities and there are various events and entertainments over the week.
Patients will receive meals on the ward. There are various outlets spanning the hospital site for meals or conveniences.
Covering technical aspects of care, the HSCT service is supported by:
- a bespoke stem cell lab on site. This specialised laboratory is accredited with the Human Tissue Authority (HTA) and the Joint Accreditation Committee for ISCT and EBMT (JACIE). The role of the laboratory is to provide high quality haemopoietic progenitor cell preparations and related products for stem cell transplantation, and
- specialised pharmacy services. Given the range of medicines used in the HSCT process our pharmacists work hand-in-hand with doctors to consider the medicine that is likely to give the biggest benefit and least side effects. Our highly specialised paediatric pharmacy team have many years experience in a wide-variety of treatment options. Some specialise in the field of advanced therapy medicinal products (ATMPs) which the stem cell transplants are one of. Others specialise in establishing the pharmaceutical elements of clinical trials when we use new drugs.
Research
HSCT is a relatively new treatment pathway, and evidence is rapidly growing showing that it can give benefits to a range of conditions. In particular HSCT is proving significant benefits for children with leukaemia, cancers, and inborn errors of metabolism.
Our HSCT service, along with its highly experienced multi-disciplinary team and bespoke facilities, caters to patients (and their families) with a range of conditions.
Our research themes include:
- Lysosomal storage disorders (LSD), such as mucopolysaccharide (MPS) diseases (e.g. Hunter Syndrome, Sanfilippo Disease) in partnership with the Willink Unit
- Acute lymphoblastic leukaemia
- Neuroblastoma
- Kidney tumours
- Ewing’s sarcoma
- Rhabdomyosarcoma & other soft issue sarcomas
- Hodgkin’s disease
- Non-Hodgkin’s lymphoma
- Intracranial germ cell tumours
For more information, visit our dedicated research pages here.