By:
Louis A. Cona, MD
Reviewed:
Robert J. Hancock
This article will explain what Haematopoietic stem cell transplantation (HSCT) involves, its benefits/risks, and how it may or may not be helpful for certain neurological conditions.
Hematopoietic stem cell transplantation (HSCT) is a medical procedure that involves eradicating disease activity by first using cytotoxic drugs to temporarily suppress the immune system, followed by the reintroduction of autologous hematopoietic stem cells.
This procedure is used in the treatment of a variety of conditions, including Multiple Sclerosis (MS), Neuromyelitis Optica, Chronic Inflammatory Demyelinating Polyneuropathy, Myasthenia Gravis, and genetic disorders like Sickle Cell Disease (SCD).
HSCT's application in these conditions represents a significant approach in the field of medicine, with ongoing research and discussion about its effectiveness and scope.
What is HSCT?
Hematopoietic stem cell transplantation (HSCT) is a treatment approach that aims to eliminate disease activity by first eradicating the immune system using cytotoxic drugs (chemotherapy) followed by the introduction of autologous hematopoietic (blood-derived) stem cells to aid in re-building the lost immune system. (1)
HSCT for Multiple Sclerosis (MS)
HSCT for MS is an intense chemotherapy treatment for MS. The aim is to destroy the immune system, then build it back up with with hematopoietic stem cells
A large number of uncontrolled studies have been published throughout the years which have established that HSCT treatment can have an effect on inflammation in MS and it can prevent relapses and new MRI lesions. (1)
According to the National MS Society, only certain people with MS may be candidates for Hematopoietic stem cell transplantation (HSCT). The best candidates for this procedure are people under the age of 50, have had MS for 10 years or less, or have relapsing MS and have had “breakthrough” disease activity (new inflammatory MS lesions in the central nervous system, and/or clinical relapses) despite treatment with a highly effective disease-modifying therapy (or for whom the use of a highly effective disease-modifying therapy is contraindicated) (6)
Success Rate
The success rate of HSCT for MS is significantly influenced by the presence of gadolinium-enhancing lesions before the procedure. A Swedish study focusing on autologous hematopoietic stem cell transplantation (HSCT) in treating aggressive multiple sclerosis (MS) has shown promising results. The study, involving 41 patients, revealed significant improvements in both clinical and radiological outcomes over a period of 5 years.
Notably, the study indicated that patients with gadolinium-enhancing lesions prior to HSCT experienced more favorable outcomes. Despite these encouraging findings, it's essential to understand that HSCT is a high-risk procedure, generally reserved for patients with severe MS cases unresponsive to other treatments.
Continued research and clinical trials are needed to fully ascertain HSCT's efficacy and safety in MS treatment. The study's significance lies in its potential to shape future MS treatment protocols at experienced centers.
Key Findings:
41 patients with aggressive MS were analyzed.
Relapse-free survival rate at 5 years was 87%.
MRI event-free survival stood at 85%.
EDSS score progression-free survival was 77%.
Disease-free survival (no relapses, no new MRI lesions, no EDSS progression) reached 68%.
Favorable outcomes were noted in patients with gadolinium-enhancing lesions before HSCT (79% vs 46%, p=0.028).
Important Considerations:
HSCT is a high-risk procedure with potential serious side effects.
Typically used for aggressive MS forms not responding to other treatments.
More research is necessary to establish HSCT's efficacy and safety in MS treatment.
For detailed information, see the study on PubMed. Further insights into HSCT for MS can be found in additional sources such as PMC, PubMed, PubMed, and PMC.
Recovery Time
In general, the initial recovery period, during which the patient's immune system begins to rebuild itself, recovery typically takes around 2 to 3 weeks. This is the period when the patient is most vulnerable to infections and other complications, and they are usually hospitalized during this time.
After this initial recovery period, it can take several months to a year or more for the patient to fully recover. This includes time for the immune system to fully reconstitute and for the patient to regain strength and recover from the side effects of the treatment. It's also during this period that improvements in MS symptoms may begin to be seen.
Does HSCT Cure MS?
No, HSCT is not considered a definitive cure for MS. The progression-free survival after HSCT varies widely, ranging from 47% to 100%. This suggests that while some patients may experience a long period without disease progression following HSCT, others may not see the same benefits.
HSCT can be a beneficial treatment for some patients with MS, particularly those with aggressive or refractory disease, it is not considered a cure. The effectiveness of HSCT can vary widely between patients, and further research is needed to fully understand its potential benefits and limitations in the treatment of MS.
Autologous HSCT
There is growing evidence that aHSCT may be highly effective for people with relapsing MS who meet very specific characteristics[5]. However, the success rate for people with progressive MS is lower, at about 70%. It is important to note that HSCT cannot regrow nerves or repair damaged myelin, so it may not be helpful for those with advanced progressive MS who no longer have relapses and don't show signs of inflammation on an MRI.
HSCT carries risks and side effects, including hair loss, fever, nausea, and infertility. The risk of infections in the future also increases. Some patients may develop acute graft-versus-host disease (GVHD) after allogeneic transplant, with symptoms such as rash, burning, redness of the skin, nausea, vomiting, stomach cramps, diarrhea, loss of appetite, and jaundice.
The costs of HSCT can vary widely, ranging from approximately $87,000 to $300,000. Factors influencing the cost include the type of transplant, conditioning regimen, hospitalization, and geographic location. It is important to consider the potential risks, benefits, and costs of HSCT when deciding whether it is the right treatment option for an individual with MS.
Risks & Benefits
The risks and benefits of hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) patients vary depending on the individual's specific condition and the type of HSCT performed. Autologous HSCT (aHSCT) is considered the safest form of HSCT for MS, as it uses the patient's own stem cells rather than donor stem cells.
Benefits of HSCT for MS patients include:
1. Reduction in relapses and stabilization or improvement of disability for some patients, particularly those with highly active MS.
2. Halt of disease activity in some cases, preventing further progression.
Risks and side effects of HSCT for MS patients include:
1. Chemotherapy-related side effects such as hair loss, fever, nausea, and infertility.
2. Increased risk of infections in the future.
3. Potential organ damage, infection, and bleeding.
4. In the case of allogeneic transplant, the risk of acute graft-versus-host disease (GVHD) with symptoms like rash, burning, redness of the skin, nausea, vomiting, stomach cramps, diarrhea, loss of appetite, and jaundice.
It is crucial for individuals considering HSCT for MS to consult with a medical professional to weigh the potential risks and benefits of the treatment based on their specific condition and needs.
Recovery Process
The recovery process after hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) can vary depending on the individual and the intensity of the treatment. Typically, people need between 3 and 6 months to recover from HSCT, but for some, it can take more than a year to fully recover. The immune system begins to recover around 2 weeks after the infusion of blood stem cells.
During the recovery period, patients may undergo rehabilitation to optimize their management and overall outcome. However, there is no established rehabilitation pathway for MS patients either before or after HSCT, and the provision of rehabilitation may vary from country to country. Rehabilitation plans should factor in the patient's initial presentation and their response to HSCT, particularly if they become systemically unwell and deconditioned during the treatment period.
Rehabilitation may include a combination of (neurological) physiotherapy, ergotherapy, psychology, relaxation therapy, and cognitive training, as well as exercise therapy in a rehabilitation room and swimming pool. At the end of the rehabilitation, the patient is given clear instructions on how to continue working towards recovery, and the healthcare provider may keep in touch with the patient about further progress in their home environment.
It is important to note that the recovery process can be different for each individual, and it is crucial to consult with a medical professional to develop a personalized recovery plan based on the patient's specific needs and condition.
Common Side Effects
Common side effects of HSCT for MS patients during recovery include:
1. Fatigue and weakness
2. Temporary loss of appetite
3. Increased risk of bleeding and bruising
4. Worsening of MS symptoms for some time
5. Hair loss, which is usually temporary (lasting between one and six months) and may result in hair growing back with a slightly different color or texture
Additionally, patients may experience side effects from the chemotherapy used in HSCT, such as fever, gastrointestinal effects, and infections. It is important to note that the recovery process and side effects can vary among individuals, and patients should consult with their medical team to discuss their specific situation and potential side effects during recovery.
Bone Marrow Transplantation (HSCT) can be broken down into four separate parts:
1) Mobilization: drugs are administered to help mobilize hematopoietic stem cells from bone marrow (stimulate stem cell production within bone marrow stem cells & promote release into the blood) (5)
2) Harvest: the cells are obtained/extracted from the patients bone marrow (autologous cell extraction)
3) Conditioning: cytotoxic drugs (chemotherapy) or radiation are used to "destroy" or "reset" the immune system
4) Infusion: administration of autologous Hematopoietic stem cells (HSCs) derived from bone marrow to help speed up recovery. The immune system can take up to 3-6 months to rebuild itself.
Eliminate the immune system
A recently published study by Burman et al. states that the basis of HSCT operates on the belief that the origin of neurological conditions lie exclusively in the immune system and is dependant on immunological memory. (1) Thus if the immune system is destroyed, it will be reset and therefore will not malfunction as it did previously.
According to Burman et al. one misconception is that the Haematopoietic stem cells (HSCs) are the therapeutic product which they are not.
"HSCs do not differentiate into neurons, and there is no evidence that they can repair damaged central nervous system (CNS) tissue."
The term "autologous hematopoietic stem cell transplantation" can be misleading since the autologous stem cells are a supportive blood product that helps to speed up recovery after intense immunosuppressive therapy. (1)
Therefore Haematopoietic stem cell transplantation (HSCT) should generally be considered a form of high dose immunosuppressive therapy with hematopoietic stem cell support. Rather than an alternative type of stem cell therapy.
What are hematopoietic stem cells?
Also known as stem cells obtained from blood. A hematopoietic stem cell is a type of stem cell that can develop into all types of blood cells, including red blood cells, white blood cells, and platelets. (3) Hematopoietic stem cells can be found in the peripheral blood and bone marrow, the stem cells must first be mobilized via certain drug administration before extraction from the patient.
What is hematopoietic stem cell transplantation (HSCT) used for?
Hematopoietic stem cell transplantation (HSCT) can be used for a variety of neurological or neuroinflammatory conditions such as Multiple Sclerosis (MS), Neuromyelitis Optica, Chronic Inflammatory Demyelinating PolyNeuropathy, and Myasthenia Gravis. HSCT has also shown the ability to help patients with Sickle Cell Disease (SCD), a genetically inherited red blood cell disorder.
What are the side effects of HSCT?
According to Burman et al., there can be a variety of adverse reactions from Hematopoietic stem cell transplantation (HSCT). These are divided into long-term side effects and acute toxicity (describes adverse effects of a substance in a short amount of time). (1)
Short term side effects
Some of the short term side effects of HSCT are alopecia (loss of hair), anemia, leucopenia (lowered white blood cell count - a decrease in disease-fighting cells in your body), and fever with or without a blood bacterial infection. Antibiotics are commonly needed to help combat bacterial infections that may occur after cytotoxic drug intake.
These short term side effects or acute toxicity is directly related to the intensity and invasiveness of the cytotoxic immunosuppressive treatment and damaged immune system.
Long term side effects
Long term side effects have been much less studied. Burman describes this as a major gap in the knowledge base of Hematopoietic stem cell transplantation (HSCT) as a treatment. "The main concerns are viral reactivations, development of secondary autoimmunity, malignancies and impaired fertility." (1)
Chemotherapy can also cause a variety of other long term health problems including: heart issues including Congestive heart failure (CHF), Arrhythmia, and Coronary artery disease; lung issues, endocrine system problems, hormonal problems, bone joint and soft tissue problems such as osteoperosis, digestive issues and brain / spinal cord problems. (9)
Cord Blood and HSCs
Cord blood is the blood that remains in the umbilical cord and placenta after a baby is born. It is a rich source of haematopoietic stem cells (HSCs), which are a type of stem cell that gives rise to all of the different blood cells in the body, including white blood cells, red blood cells, and platelets.
Haematopoietic stem cell transplantation (HSCT) is a medical procedure in which HSCs are transplanted from one individual to another in order to treat a variety of conditions, such as blood disorders, immune system disorders, and certain types of cancer. Cord blood can be used as a source of HSCs for HSCT, and it has several advantages over other sources of stem cells.
One advantage of using cord blood for HSCT is that it is less likely to cause graft-versus-host disease (GVHD) than other sources of stem cells, such as bone marrow or peripheral blood. This is because cord blood stem cells are less mature and have not yet been exposed to the same range of antigens as stem cells from other sources, making them less likely to attack the recipient's body. Cord blood stem cells are also easier to match with the recipient, which further reduces the risk of GVHD.
In addition to these advantages, cord blood is also a readily available source of stem cells, as it can be collected immediately after birth and stored until it is needed for transplantation. However, one disadvantage of using cord blood for HSCT is that it contains a smaller number of stem cells than other sources, so it may not be suitable for adults or for certain types of transplants.
Is HSCT FDA Approved?
Only the individual medications and procedures that encompass Hematopoietic stem cell transplantation (HSCT) have been approved by the FDA. These include cytotoxic drugs, radiation, chemotherapy, antibiotics, etc. However, HSCT as a treatment for specific conditions has not yet been approved by the FDA. Currently, to participate in a bone marrow transplantation within the United States, MS patients must enroll in an active clinical trial.
How does HSCT differ from mesenchymal stem cell therapy (MSCT)?
Many peer-reviewed studies over the years have found that mesenchymal stem cell therapy (MSCT) has strong anti-inflammatory and immunosuppressive properties. The intravenous administration of mesenchymal stem cells (MSCs) can improve the healing of neural, renal, and lung injuries in many different models. (7) Mesenchymal stem cell therapy (MSCT) also can induce large periods of remission and may help improve MS symptoms including; loss of strength, mobility, flexibility, numbness, and overall mobility.
The two treatment options (HSCT & MSCT) aim to achieve the same outcome: prevent relapses, new MRI lesions, and improve disability.
Mesenchymal stem cell therapy (MSCT) aims to prevent relapses, new MRI lesions, and improve disability without the need for invasive cytotoxic immunosuppression therapy (Chemotherapy). MSCT can reduce inflammation and regulate the immune system, both of which play a strong role in helping improve MS symptoms and promote disease remission.
According to a recent study published by Regmi and colleagues:
"The immunosuppressive activities of MSCs are initiated by cell-to-cell contact and the release of immunoregulatory molecules. By doing so, MSCs can inhibit the proliferation and function of T cells, natural killer cells, B cells, and dendritic cells, and can also increase the proliferation of regulatory T cells." (8)
Choose the treatment that is right for you
Hematopoietic Stem Cell Transplants (HSCT) have shown mostly positive results in treating autoimmune diseases like Multiple Sclerosis, where the immune system attacks the body. This treatment aims to "reset" the immune system, potentially stopping the disorder's effects.
However, the involvement of chemotherapy and associated risks can be a deterrent for many patients, especially those in poor health. Initially, HSCT had a concerning 1 in 100 death rate, though safety has significantly improved over time.
On the other hand, Mesenchymal Stem Cell Therapy (MSCT) offers a less invasive alternative. It's particularly suitable for patients seeking effective treatment without the risks of chemotherapy or those too frail for HSCT. MSCT's non-invasive nature also allows for repeated treatments without cumulative body damage.
Unlike HSCT, which is a high-dose immunosuppressive therapy, MSCT provides similar outcomes without aggressive drugs. Additionally, cord tissue-derived MSCT is notable for its low risk of immune rejection, enhancing the body's healing capabilities with strong anti-inflammatory and immunosuppressive effects.
Graft Versus Host Disease and Bone Marrow Transplant
Graft Versus Host Disease can occur when the HSCs from the donor (the "graft") recognize the recipient's body (the "host") as foreign and launch an immune response against it. This can lead to the destruction of healthy cells in the host's body, leading to a range of symptoms, including skin rash, diarrhea, liver damage, and difficulty breathing. Graft Versus Host Disease (GVHD) can be severe or even life-threatening in some cases.
To reduce the risk of Graft Versus Host Disease (GVHD), doctors will often try to match the donor and recipient as closely as possible in terms of their human leukocyte antigens (HLAs), which are proteins found on the surface of cells that help the immune system distinguish between self and non-self. However, even when the donor and recipient are well-matched, there is still a risk of GVHD occurring.
So does the immune system need to be destroyed to effectively help neurological conditions such as MS?
No, it does not. Published studies have found that Mesenchymal stem cell therapy (MSCT) can reduce inflammation and regulate the immune system, without the need for invasive immunosuppressive treatments (chemotherapy). MSCs derived from umbilical cord tissue also offer intrinsic benefits that hematopoietic stem cells do not, such as the ability to differentiate into a variety of cell types, release of immunoregulatory molecules, promote the release of exosome and growth factors.
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Glossary:
Hematopoietic: relating to, or involved in the formation of blood cells
Autologous: derived from the same individual, or involving one individual ad both donor and recipient
Allogeneic: involving, derived from, or being individuals of the same species that are sufficiently unlike genetically to interact antigenically
References:
(1) Burman, J., Tolf, A., Hägglund, H., & Askmark, H. (2018, February). Autologous haematopoietic stem cell transplantation for neurological diseases. Retrieved December 09, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800332/
(2) Hematopoietic Medical Definition. (n.d.). Retrieved December 09, 2020, from https://www.merriam-webster.com/medical/hematopoietic
(3) NCI Dictionary of Cancer Terms. (n.d.). Retrieved December 10, 2020, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hematopoietic-stem-cell
(4) Bhatia, M., & Sheth, S. (2015, July 10). Hematopoietic stem cell transplantation in sickle cell disease: Patien: JBM. Retrieved December 10, 2020, from https://www.dovepress.com/hematopoietic-stem-cell-transplantation-in-sickle-cell-disease-patient-peer-reviewed-article-JBM
(5) Bone Marrow Stem Cell Transplant – HSCT. (2020, December 04). Retrieved December 11, 2020, from https://www.nationalmssociety.org/Research/Research-News-Progress/Stem-Cells-in-MS/Bone-Marrow-Stem-Cell-Transplant-%E2%80%93-HSCT
(6) National MS Society Releases Recommendations for HSCT-Bone Marrow Transplant for MS. (2020, November 11). Retrieved December 11, 2020, from https://www.nationalmssociety.org/About-the-Society/News/National-MS-Society-Releases-Recommendations-for-a
(7) Sundin, M., Barrett, A., Ringdén, O., Uzunel, M., Lönnies, H., Dackland, A., . . . Blanc, K. (2009, September). HSCT recipients have specific tolerance to MSC but not to the MSC donor. Retrieved December 11, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747778/
(8) Shobha Regmi, Shiva Pathak, Jong Oh Kim, Chul Soon Yong, Jee-Heon Jeong, Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives, European Journal of Cell Biology, Volume 98, Issues 5–8, 2019, 151041, ISSN 0171-9335, https://doi.org/10.1016/j.ejcb.2019.04.002. (http://www.sciencedirect.com/science/article/pii/S0171933519300378)
(9) Long-Term Side Effects of Cancer Treatment. (2020, December 10). Retrieved December 11, 2020, from https://www.cancer.net/survivorship/long-term-side-effects-cancer-treatment
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