Overview

Initially designed for treating hematological cancers, over the past 50 years, this technique has been widely utilized to treat aggressive hematological cancers, including leukemia and lymphoma (Appelbaum FR, 2017). This procedure has been modified for use in severe immune-mediated disorders such as MS (Fassas et al., 1997) (Burt et al., 2015) (Muraro et al., 2017) (Burt et al., 2021).

AHSCT is a stem cell therapy that uses the patient’s own cells to replace those in the immune system that mistakenly attacks the CNS. Chemotherapy is employed to reset the immune system by destroying certain types of cells, followed by reinfusion of the stem cells to help rebuild a healthier immune response.

AHSCT is a validated, one-off treatment and a multistep procedure that requires a coordinated, multidisciplinary team.

Table from Muraro et al.Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder — recommendations from ECTRIMS and the EBMT“. Nature Rev Neurol (2025).

The entire procedure consists of three main phases: pre-AHSCT, AHSCT and post-AHSCT (i.e., prophylaxis and vaccinations): 

Practical Guidelines

A guidance for practical management of AHSCT in MS has been published by a task force of German experts: the Clinical Competence Network Multiple Sclerosis (KKNMS), the German Working Group for Haematopoietic Stem Cell Transplantation and Cellular Therapy e.V. (DAG-HSZT), and the German MS Self-Help Association (DMSG) (Bayas et al., 2023).

Click here for the EBMT guidelines and recommendations about practical management of AHSCT.

Figure modified from Jessop et al.General information for patients and carers considering haematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (ADs): A position statement from the EBMT Autoimmune Diseases Working Party (ADWP), the EBMT Nurses Group, the EBMT Patient, Family and Donor Committee and the Joint Accreditation Committee of ISCT and EBMT (JACIE)” Bone Marrow Transplantation (2018).

Explore AHSCT in this brief video: learn how the procedure works and how it resets the immune system.

📌 For the full version of this video, click here.

Pre-AHSCT

Below a list of key points to consider before undergoing transplant, to be evaluated together with the multidisciplinary team.

First and foremost, eligibility criteria outline the required or acceptable patient characteristics necessary for suitability for transplant. This is a crucial aspect that needs careful consideration and in-depth discussion with the multidisciplinary team supporting the patient through the decision-making process.

Detailed information on these criteria is available in our AHSCT Eligible Patient section. Click on the “Types of MS & AHSCT” section for further information.

It is important to note that each AHSCT Center may have its own specific inclusion/exclusion criteria. Please note that, every patient should consult with their neurologist to discuss their individual case and determine the best course of action.

Neurologist and haematologist must inform pwMS before undergoing AHSCT. All the topics of the written Informed Consent form must be clarified and discussed possibly in the presence of relatives.

The AHSCT procedure, the opportunities but also the risks, especially the mortality risk, the risk to fertility, and the long-term risks of cancer and secondary autoimmune diseases must be addressed.

In order to reduce the risk of adverse effects the following investigations and screening for infections precede the AHSCT procedure: ECG (electrocardiogram), echocardiogram, chest X-ray, pulmonary function test, abdominal sonography, ENT (Ear, Nose, and Throat), dental presentation and negative pregnancy test.

Screening in all patients includes: CMV (Cytomegalovirus), EBV (Epstein-Barr virus), VZV (Varicella-zoster virus), HSV1 (Herpes simplex virus type 1), HSV2 (Herpes simplex virus type 2), HIV (Human immunodeficiency virus), hepatitis viruses (e.g., HBV, HCV) and toxoplasmosis.

Additional screenings, such as those for tuberculosis and COVID-19 may be required depending on geographical location and the patient’s clinical history (i.e., anamnesis).

Cy used in the AHSCT can lead to germline damage (oocytes and sperm). Therefore, fertile female patients should be advised about egg freezing prior to treatment, and male patients should be advised about sperm preservation.

Fertility preservation in males

Limited data are available on male infertility (Tichelli et al., 2014). AHSCT could represent a risk, depending on patient characteristics and the conditioning regimen used.

Sperm cryopreservation is an established fertility preservation option for post-pubertal boys and men. Sperm can be used either for artificial insemination or, if the quantity and/or quality of sperm are insufficient, for intracytoplasmic sperm injections for in vitro fertilization.” (Salooja et al., 2024 – EBMT handbook). 

In the study Mariottini et al. (2021) 23 females (17 RRMS and 6 SPMS) and 6 males (3 RRMS and 3 SPMS) were monitored before undergoing AHSCT (27 with BEAM/ATG and 2 females received reduced-intensity regimens due to safety concerns.). 17 out of 29 had received chemotherapy-based immunosuppression prior to AHSCT.

All 6 male patients received BEAM+ATG regimen. “In males post-AHSCT testosterone levels were within normal range in 5 out 6 available cases. Testosterone levels at follow-up were not reduced compared to baseline in 2/3 (67%) cases who had the baseline assessment.”

AHSCT may affect AMH levels and ovarian reserve, as evidenced by persistent amenorrhea in 19 out of 23 females following the transplant. Recovery of menstrual function was more common in younger patients (Mariottini et al., 2021).

Fertility preservation in females

  • Embryo and Oocyte Cryopreservation: Carbone et al., 2023
  • Gonadotropin-Releasing Hormone Agonists (GnRHa): Several reports focus on the increasing risk of relapses with GnRHa; however, a recent review that included 225 women undergoing a total of 338 IVF procedures showed that there are no risks of relapses if DMTs are maintained until IVF (Mainguy et al., 2022).
  • Ovarian Tissue Cryopreservation (OTC): Colmorn et al., 2023

Burman et al. (2014) during the follow-up period (with a mean follow-up time of 47 months), there were a total of 8 pregnancies among 4 women (from a cohort of 26 wMS included in this study). Of these pregnancies: 5 resulted in healthy infants (including one set of twins). There were also 2 spontaneous abortions and 1 ectopic pregnancy. Additionally, one legal abortion was performed. Moreover, 1 man fathered a healthy child through IVF with cryopreserved semen, and 1 woman gave birth to a healthy infant following IVF with cryopreserved eggs after an otherwise normal pregnancy.

📌 Here an extended review on fertility preservation from an expert panel: “Assisted Reproductive Techniques in Multiple Sclerosis: Recommendations from an Expert Panel” (Oreja-Guevara et al., 2023).

AHSCT

During this phase, the patient’s own hematopoietic stem cells are collected and processed, followed by their reinfusion after targeted preparation. This process aims to restore the patient’s immune system, thereby reducing the autoimmune activity that characterizes MS.

Following, the phases that characterize AHSCT are described:

Mobilization

In the weeks or months leading up to the transplant, the patient undergoes a stem cell mobilization procedure to collect stem cells that will be used in the later transplantation process (Das et al., 2019, Roberts et al., 2020).

HSCs reside in the bone marrow. HSCs mobilization refers to the process of stimulating the release of stem cells from the bone marrow into the bloodstream, typically through the administration of granulocyte colony-stimulating factor (GSF), either alone or with cytotoxic chemotherapy, such as Cy (Muraro et al., 2017).

Figure from Mariottini et al.Hematopoietic Stem Cell Transplantation for the Treatment of Autoimmune. Neurological Diseases: An Update“. Bioengineering (2023) 

Harvest & Cryopreservation

Hematopoietic stem cells (HSCs) are now collected from peripheral blood through leukapheresis, a procedure that separates white blood cells from the bloodstream. In some cases, the graft is purified using CD34 immunomagnetic selection to remove mature immune cells.

After collection, HSCs are cryopreserved until transplantation. The recommended storage amount is 3–8 × 10⁶ CD34⁺ cells/kg, with an additional 2.5 × 10⁶ CD34⁺ cells/kg as a backup. A minimum of 3 × 10⁶ CD34⁺ cells/kg is required for reinfusion (Bayas et al., 2023).

Conditioning Regimen

The goal is to eliminate existing immune cells. The transplant conditioning regimen start generally more than 3 weeks after mobilization. Various conditioning regimens are available and are classified according to the guidelines set by the EBMT.

According to the EBMT guidelines, the conditioning regimens for AHSCT in MS are classified as high, intermediate and low conditioning regimens. However, due to the unacceptable morbidity, high TRM, and short- and long-term toxicity associated with high-intensity protocols, they are no longer recommended for AIDs.
 
Instead, less toxic regimens have been adopted. The EBMT registry indicates (Sharrack et al., 2019) that two intermediate-intensity regimens are the most commonly used: Cy 200 mg/kg + ATG and BEAM+ATG. See figure here.
 

Types of conditioning protocols:

All the following images were designed and kindly provided by Bram Platel from msinbeeld.nl.

The protocols may vary slightly depending on the AHSCT Center performing the transplant and the specific conditioning regimen chosen. For the AHSCT centers accredited by EBMT (JACIE), here. The following are the most common conditioning regimens used for MS:

Figure from msinbeeld.com

For the source article on the intermediate intensity protocol: Mancardi et al.Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis” (2017)

Figure from msinbeeld.com

For the source article on the low-intensity protocol: Laureys et al. A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis” (2018). 

More useful information:

🔍 A total of 65 centres have achieved JACIE accreditation in 2023, click here.

🔍 A report on centres in the process of being accredited, click here.

Figure from Mariottini et al. ” Hematopoietic Stem Cell Transplantation for the Treatment of Autoimmune Neurological Diseases: An Update”. Bioengineering (2023)

 

Reinfusion

Immediately after completion of the conditioning regimen, patients develop pancytopaenia and a transient bone marrow aplasia, and intravenous infusion of the stored HSCs (transplantation) is required to enable bone marrow repopulation, recovery of haematopoiesis, and immune reconstitution.” (Muraro et al., 2017).

This phase is considered as day “0” of the transplant. The patient’s own HSCs are reinfused, initiating the gradual recovery from the aplastic phase and promoting the reconstitution of the immune system.

Post-AHSCT

The post-AHSCT phase is critical period for the long-term success of the transplant and the prevention of complications. During the first months, continuous care and follow-up are essential to minimize the risk of TRM and ensure optimal recovery.

After reinfusion, patients remain in hospital until engraftment is confirmed according to site guidelines.” (Bayas et al., 2023). 

This is the period with the highest risk of infections. Read more on infections here or about transplant-related mortality here

If required, transfusions should be administered. “All blood products for administration in the first year after transplantation must be irradiated. CMV-negative patients should be transfused only with CMV-negative blood products or with an appropriately adapted system” (Bayas et al., 2023). 

All patients should remain under the direct routine care of the transplant programme specialist for at least 100 days post-transplant, or longer if needed, until clinically stable.

After discharge, all AHSCT patients are monitored weekly as outpatients for up to 1 month after transplantation. All patients are monitored weekly for CMV and EBV by PCR in peripheral blood until day 30 and at every visit thereafter”. (Bayas et al., 2023)

Prophylaxis is performed for herpes simplex virus reactivation and against Pneumocystis jirovecii infections.

Other infection prophylaxis is given according to local protocols and in case of persistent neutropenia.

As noted by Bayas et al., vaccination protection for all vaccinations is usually lost after AHSCT. Vaccination recommendation, and a comprehensive study covering various aspects of immune reconstitution after transplant for MS was published on behalf of the EBMT Autoimmune Disease Working Party (Cencioni et al., 2022).

“Post-transplant vaccinations should be given according to the recommendations of the transplant societies with individual risk assessment in the MS context.” Bayas et al., 2023.

Post-transplant vaccinations should be started 3 months after transplant with inactivated vaccines and 24 months after transplant with live attenuated vaccines, according to guidelines.

According to EBMT guidelines, titre checks before vaccination are not recommended, and vaccinations can be carried out according to local standards.

The following a detailed table of vaccination by (Bayas et al., 2023): 

 

Long-Term Monitoring

Typically, three months after the transplant, the patient undergoes an initial MRI, followed by subsequent MRI every six months.

From the second year onward, the frequency is reduced to once per year, accompanied by both neurological and hematological evaluations. Specific blood tests are not required at this stage.

In the event of suspected relapse, a neurological evaluation is mandatory.

AHSCT Centers & Costs

Availability and reimbursement of AHSCT worldwide (list in progress)

Reimbursement criteria and availability vary between countries and may change over time. 

Germany 2023: “In Germany, AHSCT for MS in general is not paid for by insurance companies and hence is only performed on an individual basis and expert opinion. Therefore, coverage needs to be negotiated from case-to-case and after rejection of compensation from insurance companies, patients need to pay on their own. Some try to reach out for a social court verdict.” (Bayas et al., 2023)

Italy: AHSCT is available and paid by the National Health Service (Mariottini et al., 2024)

Since December 2022, AHSCT is covered by basic health insurance but only for a highly specific patient group. Strict eligibility criteria apply: age 18-55, RRMS with disease duration <10 years, EDSS 3.0-6.5, and failed response to at least one highly effective DMT despite 6 months of treatment. Treatment is currently performed in two centers (Amsterdam UMC and St. Antonius Hospital Nieuwegein) following mandatory review by a National Indication Committee (Zorginstituut Nederland, 2022).

Poland 2021: “AHSCT is fully financed by the National Health Found for patients with MS owing to the structure of AHSCT reimbursement in Poland” (Orlewska et al., 2021)

Sweden 2025:In Sweden, AHSCT is approved by the Swedish Board of Health and Welfare for use in aggressive RRMS, whereas SPMS and PPMS are not endorsed.” (Mitrache Desaga et al., 2025)

Switzerland 2021: Since 2018, AHSCT is available and reimbursed by the health care providers as long as patients agree to be enrolled in a registry study (BASEC-Nr. 2018-01854). (Stathopoulos et al., 2021)
UK 2024: In the UK, AHSCT can be covered by the NHS. For more details click MS Trust, UK.

USA: “The average total cost of care for inpatient aHSCT in the U.S. is $150,000. This usually includes the care required before and after the procedure. However, the cost of aHSCT varies widely. Prices are based on the patient and their treatment plan.Most insurance companies will probably not cover this procedure. Expect to pay for it out of pocket or enroll in a clinical trial where the costs are covered by the trial.” ” (National MS Society, 2025)

HSCT mean total costs, based on our own hospital [Northwestern Memorial Hospital in Chicago], were $85,184 (range $70,635 to $120,260). Mean revenue collected was $95,268 (range $16,544 to $173,204). In comparison, according to the literature, 2019 DMT costs in the USA ranged from $80,000 to $100,000 per year per patient.” (Burt et al., 2020).

A detailed description of the procedure for obtaining a possible reimbursement is provided in Prof. R.K. Burt’s book (page 105: “Insurance approval” section).

Some Neurological and Hematological Centers that performed AHSCT in MS

The following is a list of centres worldwide that, to the best of our knowledge, perform AHSCT in MS (the list is not exhaustive and is continuously updated).

A center to be included in the list must satisfy the following criteria:

  • Certification: by the European EBMT-JACIE, or equivalent international accreditation, such as the Joint Commission International (USA).
  • Conditioning regimen: use intermediate-intensity regimens such as CY-ATG (non-myeloablative, also called lymphoablative) or BEAM-ATG (myeloablative), as reported in the consensus statement (Muraro et al., 2025).

The year of the latest scientific publication and the trial, if the center is involved, are reported in bold.

✅ Useful link: ongoing AHSCT trials here

Country

Hospital

Australia Department of Neurology, St. Vincent’s Hospital, Darlinghurst, 2023
Canada Department of Medicine (Neurology), The University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, 2025
Czech Republic Department of Neurology, University Hospital Ostrava, 2023
Denmark Danish Multiple Sclerosis Center (DMSC), Copenhagen University Hospital – Rigshospitalet (Copenhagen), 2023 RAM-MS Trial
Germany University Medical Center Hamburg-Eppendorf, 2025
India
  • HSCT Hospital, New Delhi NCR
  • Department of Hematology and BMT, Fortis Memorial Research Institute, Gurgaon, Haryana, 2020
Israel

Hadassah University Hospital, Jerusalem, Ein-Kerem, 2020

Italy
  • Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università di Genova/Italy, 2025 | NET-MS Trial
  • Neurology II Department & Cell Therapy and Transfusion Medicine Unit, University Hospital Careggi, Florence/Italy, 2025 | NET-MS Trial
  • Neurology I Department & Cell Therapy and Transfusion Medicine Unit, University Hospital Careggi, Florence/Italy,  2025 | NET-MS Trial  
  • Department of Neurology, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan/Italy, 2025 | NET-MS Trial
  • Struttura Complessa di Neurologia & Struttura Complessa di Ematologia, Ospedale Santa Croce e Carle, Cuneo, 2023
  • Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95125 Catania/Italy, 2022
  • Department of Neurology, Ospedale Generale Regionale “F. Miulli”, Acquaviva delle Fonti, Bari/Italy, 2021
  • Multiple Sclerosis Center, Department of Medical Sciences and Public Health University of Cagliari, Binaghi Hospital Cagliari/Italy, 2021
  • Department of Neurology, CRESM, San Luigi Gonzaga Hospital, Orbassano/Italy, 2021 | NET-MS Trial
  • Department of Neurology, ARNAS Civico di Cristina Benfratelli, Villa Sofia Hospital, Palermo/Italy, 2021 | NET-MS Trial
  • UO Neurology, AUSL della Romagna, Ravenna/Italy | NET-MS Trial
  • SC Neurologia 1 U (Struttura Semplice Centro Sclerosi Multipla). Molinette Hospital, Turin/Italy
  • Ospedale Gemelli – Rome | NET-MS Trial
Lithuania

Hematology, Oncology and Transfusion Medicine Center of Vilnius University Hospital Santaros Klinikos, Vilnius, 2020

Netherlands
  • Amsterdam UMC
  • St. Antonius Hospital Nieuwegein

Norway

Haukeland University Hospital, Bergen, 2025 RAM-MS Trial

Russia

Pirogov National Medical and Surgical Center, Moscow, 2022

Spain

Hospital Universitari La Fe Valencia and Hospital Clínic Universitari of Valencia, 2017

Sweden
  • Department of Medical Sciences, Neurology, Uppsala University, 2025RAM-MS Trial
  • Sahlgrenska University Hospital, Göteborg, 2021 
Switzerland

Department of Hematology, University Hospital of Lausanne (CHUV), and University of Lausanne, Lausanne, Switzerland, 2023

Turkey Erciyes University Faculty of Medicine, Department of Internal Medicine Hematology, Kayseri, Turkiye, 2024
United Arab Emirates

Abu Dhabi Stem Cell Center, Abu Dhabi, United Arab Emirates, 2023

UK
  • Sheffield Institute for Translational Neuroscience, University of Sheffield, UK/Academic Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, 2025 | STAR-MS Trial
  • Kings College Hospital (KCH), 2025 | STAR-MS Trial
  • Hammersmith Hospital (HH) (London), 2021
USA
  • Mellen Center for Multiple Sclerosis Treatment and Research – Cleveland Clinic, 2025 | BEAT-MS Trial
  • Division of Immunotherapy, Northwestern University Feinberg School of Medicine, Chicago, IL, 2022 | BEAT-MS Trial

WARNING: SHAM STEM CELL CENTERS AND STEM CELL TOURISM

As suggested by the National MS Society USA (link here): “Some clinics in the U.S. and abroad do not have the necessary experience performing aHSCT on MS patients.

Some clinics overstate their experience online with testimonials to attract patients.

Make sure the clinics can back up their claims with peer-reviewed research. And consult your MS specialist. They can help ensure that the clinic follows strict health and safety standards.”

AHSCT: Patients' Stories

Below first-hand accounts of pwMS who have undergone AHSCT, as documented in the scientific literature:

Tolf et al., 2024: “Experiences of being treated with autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: A qualitative interview study“. PLOS ONE.

All 10 patients included in this qualitative interview study underwent AHSCT for MS at Uppsala University Hospital in Sweden between 2004 and 2007.

Melissa, sharing her experience, says that: “So I felt, I wasn’t scared or anything when he started talking about, like, there were, well, dangers, but I, like: . . . “I’ll do it, since I’ve got nothing to lose.” Since it was just getting worse and worse.”

As reported by the Authors: “The treatment itself was described as a transformative passage where life had to be temporarily suspended. After AHSCT, previously lost functions returned, with recovery of autonomy, identity, and a sense of normality in most of the participants.” (Tolf et al., 2024)

Volz et al., 2024: “A second birthday”? Experiences of persons with multiple sclerosis treated with autologous hematopoietic stem cell transplantation-a qualitative interview study“. Front. Neurol.

AHSCT represents a promising treatment for pwMS. This qualitative study explores the challenges faced by 12 patients undergoing AHSCT. Three major themes were identified: (1) preparing for aHSCT, (2) experiencing the procedure, and (3) post-treatment time.

The Authors concluded that “AHSCT had a clear impact on patients’ physical and psycho-social health, influencing their perception of life and its quality. Assessing and attending to unmet needs of patients before, during, and after transplantation may positively influence their experience of AHSCT”. 

Read the full article here.

Davenport et al., 2024: “A qualitative study on the experiences of autologous haematopoietic stem cell transplant for Multiple Sclerosis”. Multiple Sclerosis and Related Disorders.

In this study, 12 patients were included: 9 with RRMS and 3 with SPMS. Three main themes were identified to capture patients’ experiences:

(1) Balancing hope and fear explores the decision-making process prior to AHSCT; (2) Distinct emotional experiences highlights the challenges faced at all stages of the treatment journey; and (3) Adjusting to outcomes examines post-AHSCT experiences.

As indicated by the authors: “To date, research has predominantly focused on disease-specific outcome measures. There is a lack of research exploring patient experiences of this complex treatment. The study aims to explore the experience of considering and receiving HSCT treatment for MS.”

Read more here.

Other Patients' Experiences

Below is a series of additional direct experiences shared by patients and collected from various MS Association websites:

Serena, an Italian biotechnologist, researcher and mother, tells us her family story. MS has always been present in her life: first through her father’s experience, then as a researcher in an MS lab, and finally as a patient.

Here are some highlights from her interview for AISM (Italian MS Association), which you can watch here:

Then the time came when I had to make a decision. I was offered to undergo AHSCT. It was the only treatment that made me think about the future in a much more hopeful way. [ ] I have always had faith in the future. But the confidence I gained [after AHSCT was boundless”.

This patient shares various negative aspects of his AHSCT journey. Despite the treatment not being successful, Dan mentions that he would still opt for the procedure again. “Overall, I made a tough decision backed by clinical findings, data, months of research and anecdotal experiences. I do regret my choice. However, I would’ve always wondered if I didn’t try HSCT.” Read more here.

Chris has shared his personal journey through a series of YouTube videos (here). When asked what he would say to someone considering the transplant, Chris replied “Do as much research as you possibly can.”. Read more here.

Dan didn’t know what MS was before his diagnosis in 2020. When it came time to evaluate the transplant and its associated risks, Dan stated that “There are risks but for me, the reward of stopping my MS from getting any worse and having a sustained quality of life is well worth it.”. Read more here

This Australian podcast episode (by The Raw Nerve) discusses AHSCT, focusing on the treatment and associated adverse events, featuring the testimony of a patient (Michael).

Regarding his personal assessment of the potential benefits and risks, Michael states that “To be totally honest with you, I wasn’t really concerned about the risks to the point where I didn’t even start googling like a lot of people do and try and look at the doom and gloom. I was just trying to look for what was the best option to be able to move forward.”. Read more here.

Below are presented personal accounts through video narratives collected online: 

Amanda and Trudee underwent AHSCT in Chicago, and they shared their positive experiences in a CBS America report featuring Dr. Burt. See the video here.
American actress Selma Blair underwent AHSCT in the USA. Here is a touching documentary capturing Blair’s experiences before and after the procedure.

For an immersive insight into patient’s journeys, we highly recommend reading “Everyday Miracles: Curing Multiple Sclerosis, Scleroderma, and Autoimmune Diseases by Hematopoietic Stem Cell Transplant” by Prof. R.K. Burt describes AHSCT patient’s journeys, following some testimonials of MS.