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Summary
HSCT (haematopoietic stem cell transplant) is not a drug, it is a procedure that involves harvesting of stem cells that first need to be mobilised from the bone marrow using a ‘conditioning’ regimen of low-dose chemotherapy and growth factors. The stem cells are harvested from the blood and frozen down or stored. People with MS undergoing HSCT then have their immune system depleted with chemotherapy to a greater (myeloablative HSCT) or lesser extent (non-myeloablative HSCT). The stem cells are re-infused to allow more rapid recovery of bone marrow and immune function. HSCT is not a ‘licensed therapy’ for MS, but it is offered as a treatment for more active disease in many countries – typically for MS that has not responded to standard DMTs. HSCT is on the list of essential off-label DMTs because it is a generic procedure available in many countries. In other words, it can also be used for treating MS where access to high-cost licensed DMTs is limited.
Types of HSCT
- So-called myeloablative therapy aims to wipe out your immune system completely and replace it with a new immune system.
- Non-myeloablative therapy is less intense: it partially depletes your immune system and allows it to be rebooted (partially). Non-myeloablative therapy is less toxic and less risky than myeloablative therapy but also less effective.
Mode of action
HSCT is an immune reconstitution therapy (IRT). It works by depleting your immune system and allowing it to reconstitute. The hope is that when the immune system has reconstituted, the autoimmune cells that cause MS are absent.
Efficacy
Very high.
Class
Non-selective IRT, short-term immunosuppression.
Immunosuppression
Yes, short-term, whilst the immune system is depleted. Once it reconstitutes itself, the immune system is competent.
Protocols
HSCT protocols of different intensities are used to treat MS. Those used in non-myeloablative therapy are less toxic and less risky than in myeloablative therapy but also less effective:
- low intensity (non-myeloablative)
- intermediate intensity (non-myeloablative)
- high intensity (myeloablative).
Adverse events and events of particular interest
High doses of chemotherapy used as part of HSCT can cause serious adverse events. Some of the complications can be life-threatening.
Infection: during the first 6 weeks after HSCT, the risk of getting a serious bacterial or viral infection is high. You will be told what precautions to follow. It takes 3 ̶ 12 months after transplant for the immune system of most patients to recuperate.
Nausea and vomiting are common and are treated with antiemetics.
Mouth and throat pain is a short-term side effect of high-intensity chemotherapy.
Hair loss typically begins within 2 ̶ 3 weeks of treatment. Hair growth will return to normal once the treatment is finished.
Bleeding and bruising are a risk in the early weeks after HSCT; you may be susceptible to nosebleeds and bleeding gums. A platelet transfusion or red blood cell transfusion may be required.
Cardiotoxicity may result from chemotherapy, particularly in older people with MS and people who have received prior cardiotoxic drugs, for example, mitoxantrone.
Neurotoxicity is most likely in people with advanced MS and significant disability treated with high-intensity chemotherapy regimens.
Other complications may include lung problems, hepatic veno-occlusive disease, infertility, secondary autoimmune diseases, graft-versus-host disease, graft failure and secondary cancers.
Pharmacovigilance monitoring and derisking
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