An Hematopoietic Stem Cell Transplant (HSCT) is a way to treat some malignant and benign diseases. The transplant replaces disease causing bone marrow with healthy stem cells. Many of the components in the blood are made in the bone marrow and defective manufacture of them causes diseases like leukemia. There are around 50,000 such transplants done each year throughout the world.
The procedure involves completely zapping the recipient’s bone marrow and infusing healthy stem cells harvested from a healthy donor. It is a cure. It can be a cure for some leukemia and closer to home it can be a cure for PNH.
Whilst their defective bone marrow is zapped by very potent chemotherapy agents, the patient is extremely vulnerable because all the blood cells needed to live are no longer produced, no white cells , no red cells , platelets , neutrophils and so on.
All have to be provided temporarily by transfusion until the new stem cells catch and start producing the bone marrow which in turn will produce all the blood cells to levels needed in healthy blood.
Losing the means to fight infections makes the patient at risk from infections as the acquired immunity built up through a life time is destroyed, including immunity provided by vaccinations. Childhood diseases can return.
Also with a transplant there is a risk of rejection. In these transplants it is not the host rejecting the donor organ, but the donor organ ( the blood) rejecting the host. Causing an inflammatory response known as graft versus host disease, GVHD. This will continue until the new blood accepts its new host. It needs aggressive steroid treatment and all that comes with that.
Both infections and GVHD can trigger a TMA. Possibly at the same time!
The inflammation can affect the endothelial cells in the host’s capillaries and can trigger off a thrombotic microangiopathy ,TMA, the mechanism that can cause aHUS patients their problems.
HSCT- TMA, or TA-TMA is classified as a secondary TMA, or a secondary aHUS. The terminology varies. There are patients in the aHUS community whose aHUS has been triggered by an HSCT or TA.
Like all secondary TMAs it is not clear cut whether Complement is an additional factor in the progress of the disease irrespective of whether it is due to genetic causes or not. Eculizumab has been found to be effective in bringing control to Complement overaction in HSCT -TMA. . Very often much higher doses of eculizumab are needed very early on, but in time when the triggering conditions of GVHD and infection are resolved patients can usually withdraw from treatment successfully
Of the 50, 000 HSCTs each year, it is estimated that the incidence of TMA is around 12% or 6,000 patients. More than the likely 4000 incident aHUS patients each year . Very few HSCT- TMA patients will experience an aHUS, but how many is not known?
Those aHUS patients will be excluded from clinical trials for “aHUS” patients treatments.
They will need to be included in trials specific to HSCT- TMA. But how do they get recruited? It is the same problem faced by those designing aHUS trials. Identifying the right patient appearing in the right place at the right time- an effective catchment net is needed.
But treatment of an HSCT is usually done in specialised centres and potential trialists are being monitored in specialist care and not newly arriving “off the streets”. A TMA is something that should be watched for and patients should have been told about it in the risks and benefits of such transplants.
In the work up to a transplant any history of aHUS in the family would be a known but very rare risk factor. Most would not know about any genetic predisposition and would not be routinely tested.
But there must be something that should differentiate the likely TMA onsetters from the majority of HSCT patients.
In pure mathematical terms there need to sufficient total patients from the collective trial sites to produce the desired number of trial participants after allowing for the numbers of patients who would not give informed consent.
To recruit 50 trial participants in a two year recruitment period the trial investigation sites together will need to be carrying out at least 175 transplants each year and assume all give informed consent. The trial may need many more potential patients than that.
Among all leukemia patients, those having bone marrow transplants are few and those experiencing TMAs even fewer. Of those experiencing TMA even fewer are regarded as aHUS . Who advocates for them? Who do Pharma regard as advocating for them.
A random search of a selection of leukemia patient organisation websites and the response to a “thrombotic microangiopathy” query is “Sorry, we couldn’t find any results for: Thrombotic microangiopathy”
Search this site and there is much information about TMA to be found .
.How is the voice of these patients heard?
Depends on whether HSCT patient is just a TMA patient or an aHUS patient.