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Haematopoietic Stem Cell Transplantation (HSCT): Defined (2023)

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Haematopoietic Stem Cell Transplantation (HSCT): Defined (2023)

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The article analyzes the use of HSCT to reboot the immune system for treating neuroinflammatory diseases. It evaluates the procedure's steps, compares its effectiveness to alternative treatments like Mesenchymal Stem Cell Therapy, and discusses the legal and health risks involved, including lack of FDA approval and potential for Graft Versus Host Disease.

Defining HSCT

HSCT stands for hematopoietic stem cell transplantation, a medical procedure that involves the transplantation of stem cells, usually from bone marrow, peripheral blood, or umbilical cord blood, to replace damaged or diseased bone marrow.

The procedure is used to treat various blood and immune system disorders, such as leukemia, lymphoma, and multiple myeloma, as well as some non-cancerous conditions, such as sickle cell anemia and thalassemia. HSCT can be autologous, where the patient's own stem cells are used, or allogeneic, where stem cells from a donor are used.

According to a study, in 2007, 4239 HSCT transplantations were performed in France, and in Europe, in 2006, 25,050 grafts were performed, of which 61% were autologous and 39% were allogeneic.

Haematopoietic Stem Cell Transplantation (HSCT) is a potent therapeutic approach that involves the complete elimination of the immune system using cytotoxic drugs, followed by an infusion of blood-derived stem cells to reconstruct the devastated immune system. Because of their potential to develop into a variety of cell types, these distinct stem cells are a crucial component in the effective treatments of numerous diseases, particularly those of neurological nature.

HSCT infographic

What is the Therapeutic use of HSCT?

HSCT has a wide range of therapeutic uses, including the treatment of various blood and immune system disorders, such as leukemia, lymphoma, and multiple myeloma, as well as some non-cancerous conditions, such as sickle cell anemia and thalassemia [1][2]. HSCT can be autologous, where the patient's own stem cells are used, or allogeneic, where stem cells from a donor are used. In addition to these uses, recent research has explored the potential of HSCT for a variety of other nonmalignant conditions, including cardiovascular, musculoskeletal, and neurologic diseases [2].

Other therapeutic uses of HSCT include the generation of red blood cells, granulocytes, or platelets ex vivo for transfusion into difficult-to-transfuse patients [1]. Additionally, the use of regulatory T cells (Treg cells) has been explored for the prevention and treatment of graft-versus-host disease (GvHD) in HSCT recipients [5]. Finally, CAR T-cell therapy has been evaluated as a treatment for acute lymphoblastic leukemia (ALL) [6].

Process of HSCT: Mobilization, Harvesting, Conditioning, and Infusion

The HSCT process involves four stages: Mobilization, Harvesting, Conditioning, and Infusion. During Mobilization, the patient produces stem cells within the bone marrow which later move into the bloodstream. These cells are then harvested in an autologous cell extraction procedure, collected for later use. Conditioning, the next step, involves the use of cytotoxic drugs or radiation to remove harmful elements from the immune system. Lastly, the infusion of Hematopoietic stem cells is performed to accelerate the recovery process.

Role of the immune system in HSCT

The principles that underpin HSCT are closely linked to the immune system and its immunological memory. By manipulating the immune system and its functionalities, HSCT facilitates the reconstruction of a more favorable immune environment.

HSCT in Treating Neurological Conditions

The belief behind using HSCT in treating neurological disorders

The argument for applying HSCT in treating neurological disorders hinges on the belief that the root cause of these conditions lies fundamentally within the workings of the immune system. As such, by modifying the immune functions through HSCT, the progression of these disorders could potentially be arrested.

Common neurological conditions treated with HSCT: Multiple Sclerosis (MS), Neuromyelitis Optica, Chronic Inflammatory Demyelinating PolyNeuropathy, Myasthenia Gravis, and Sickle Cell Disease

HSCT has seen use in the treatment of various neurological or neuroinflammatory conditions. Among these are Multiple Sclerosis (MS), Neuromyelitis Optica, Chronic Inflammatory Demyelinating PolyNeuropathy, Myasthenia Gravis, and Sickle Cell Disease. These conditions share common characteristics of inflammation and degeneration within the nervous system, for which HSCT has shown potential benefits.

Effectiveness of HSCT in treating these conditions

The outcomes of HSCT application in these conditions are patient-specific and depend on the individual's response to therapy. Nonetheless, it has been suggested through numerous clinical studies that HSCT may bring about a control in disease activity and a potential reduction in disability, particularly in individuals with aggressive and refractory disease forms.

Potential Side Effects of HSCT

Short-term side effects: hair loss, anemia, lowered white blood cell count, fever

In the course of HSCT treatment, several short-term side effects may occur. These include hair loss, anemia, a decrease in white blood cell count, and fever. Such effects are typically due to the high-dose chemotherapy used in the conditioning phase of the treatment.

Long-term effects: viral reactivations, secondary autoimmunity, malignancies, impaired fertility

Long-term side effects of HSCT are also considerable, with possible occurrences such as viral reactivations, secondary autoimmunity, malignancies, and impaired fertility. These side effects largely stem from both the immediate and long-term consequences of the high-dose immunosuppressive therapy.

Managing these side effects

The management of these side effects generally involves supportive care and the use of medications that counteract specific side effects. For example, antibiotics or antiviral medications can be administered to manage infections resulting from lowered white blood cell counts.

Identifying Potential Candidates for HSCT

Criteria set by the National MS Society

The evaluation for potential candidates for HSCT is a rigorous process that aims to determine the patient’s potential for benefiting from the treatment. The National MS Society provides criteria for candidacy that include age below 50, less than 10 years duration of MS, evidence of inflammatory disease activity, and a relapsing form of MS.

Evaluation process for potential candidates

The comprehensive evaluation process involves an in-depth assessment of patient's disease characteristics, comorbidities, and performance status as well as careful consideration of the potential benefits and risks associated with HSCT.

What happens if a patient is not considered a suitable candidate

For patients who do not meet these specified criteria, other therapeutic options may be explored. These include other pharmacological treatments, therapeutic exercises, and symptom management strategies.

Using Cord Blood in HSCT

What makes cord blood a viable source for HSCT

Cord blood, rich in haematopoietic stem cells, represents a viable source for HSCT. The unique property of these stem cells to develop into all types of blood cells makes them valuable in this context.

Process of extracting haematopoietic stem cells from cord blood

The extraction process involves procuring cord blood shortly after birth. This blood is a rich source of stem cells that can be preserved and used in the future for transplantation procedures, including HSCT.

Benefits and risks of using cord blood in HSCT

Cord blood offers numerous advantages such as the immediate availability of cells and lower risks of complications associated with graft-versus-host disease. However, potential risks including graft failure and serious infections may also occur.

Regulatory Status of HSCT

Current FDA stance on HSCT

Despite individual medications and procedures encapsulating HSCT receiving FDA approval, HSCT as a complete treatment has not been sanctioned yet by the authoritative body.

Reasons behind lack of approval

The hesitation in granting approval could be attributed to the complex nature of HSCT, from the procedure itself to the potential side effects and complications. Moreover, the diverse range of diseases it aims to treat raises further concerns about its applicability and efficacy.

How this affects treatment possibilities

Without regulatory approval, the use of HSCT as a standard treatment option becomes limited. Despite some promising results in clinical trials and individual case studies, these interventions' recognition as standard care for certain conditions has yet to be officially sanctioned.

Comparing HSCT to Mesenchymal Stem Cell Therapy (MSCT)

Contrasting goals of HSCT and MSCT

HSCT and Mesenchymal Stem Cell Therapy (MSCT) represent contrasting therapeutic strategies. HSCT aims to entirely replace the immune system with an entirely new one, while MSCT targets reducing inflammation and regulating the immune system without the need for highly invasive treatments.

Comparing the procedures of HSCT and MSCT

While both HSCT and MSCT involve the use of stem cells, the procedures greatly differ. HSCT is more invasive, involving high-dose chemotherapy and stem cell infusion, while MSCT typically involves stem cell extraction, cultivation, and re-injection into the patient, often through minimally invasive procedures.

Side effects of MSCT compared to HSCT

MSCT generally presents fewer side effects compared to HSCT, mainly because it does not involve the harsh interventions of chemotherapy and radiation.

Therapeutic benefits of HSCT vs MSCT

Both HSCT and MSCT can offer unique therapeutic benefits. While HSCT could completely reset the immune system, MSCT may serve as a treatment alternative offering comparable benefits via a less invasive procedure.

Current evidence and clinical trials comparing both therapies

Current evidence and clinical trials therefore play a pivotal role in distinguishing between the two therapies. Comparative studies are essential in assessing the relative benefits and drawbacks of each treatment.

Risk of Graft Versus Host Disease in HSCT

What is Graft Versus Host Disease

Graft Versus Host Disease can occur in HSCT in instances where the stem cells from an allogeneic donor embark on an attack on the recipient's body, recognizing it as foreign.

How it arises in HSCT

This undesirable outcome can emerge following the infusion of donor stem cells into the patient during the HSCT procedure.

Strategies to minimize this risk

Strategies to circumvent this risk typically revolve around the careful selection of a donor whose human leukocyte antigens (HLAs) closely match those of the recipient. The development of new immunosuppressive drugs and prophylactic regimens may also aid in reducing the risk of Graft Versus Host Disease.

Looking Towards the Future: Innovations and Developments in HSCT

Current research being undertaken to improve HSCT

Presently, numerous research initiatives are dedicated to enhancing the safety and efficacy of HSCT. These efforts range from developing improved conditioning regimens, managing the long-term complications of HSCT, streamlining the procedure, and enhancing patient selection and care.

Potential new applications for HSCT

The potential for new applications of HSCT suggests an exciting future for this therapy. From advancing its use in other autoimmune and inflammatory diseases to exploring potential benefits in genetic disorders, the scope for implementing HSCT may be broadened.

Barriers to further development and how these might be overcome

Barriers to further development include complexities in regulation, high costs associated with the procedure, and potential health risks which all adversely impact the widespread accessibility of HSCT. However, with continuous research and technological advancements, these obstacles may be overcome.

Conclusion: Weighing The Potential Against The Challenges of HSCT

Summarizing the potential benefits of HSCT for neurological conditions

While HSCT holds immense potential for treating numerous neurological conditions, it is crucial to carefully weigh the benefits against the considerable challenges that come with it.

Reflecting on the challenges and limitations of HSCT

These challenges range from identifying suitable patients, managing the short-term and long-term side effects, ensuring the procedure's safety, and securing the widespread accessibility of HSCT to patients.

What the future holds for HSCT in treating neurological conditions

Despite these challenges, the future of HSCT in managing neurological conditions appears promising, provided that innovations continue to make the procedure safer, more effective, and more accessible to patients worldwide. It is, therefore, a matter of continuous research, clinical experience, and technological developments that can harness the full potential of HSCT.

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