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Stem cell therapy for relapsing MS proves effective and safe, study finds

(CNN)-An experimental stem cell therapy proved effective and safe in patients with a relapsing form of multiple sclerosis , an autoimmune disease that affects the central nervous system, new research finds.

A stem cell transplant using a lower-dose regimen of chemotherapy plus immune system suppressors is more effective at preventing disease progression compared to currently used disease-modifying therapies, according to the new study published Tuesday in the journal JAMA. (The stem cell treatment is known as “autologous hematopoietic stem cell transplantation” or HSCT.)

“I never use the word ‘cure’ — never,” said Dr. Richard K. Burt, lead author of the study and chief of Immunotherapy and Autoimmune Diseases at Northwestern University Feinberg School of Medicine in Chicago. However, only a minority of patients receiving HSCT relapse by the five year mark, he said. “The vast majority don’t.”

How does this experimental stem cell therapy work?

HSCT essentially reboots the immune system.

HSCT India“Out with the old, in with the new” is the goal, said Burt, adding that it is a “one-time treatment. You’re done, you’re off drugs.” First a patient’s blood stem cells are collected and then the patient is treated with chemotherapy drugs. Then, blood stem cells are returned to the patient to jump start the development of a new immune system.

In contrast, disease-modifying therapies work differently. These are a dozen or more drugs designed to be chronic, continuous treatment that targets and modulates the immune system. The new comparison study took place at medical centers in the US, UK, Sweden and Brazil, where 110 patients with relapsing-remitting MS participated in the randomized clinical trial, a gold standard medical test. Patients received either the HSCT protocol or a different class of disease-modifying therapy than they’d previously used.

HSCT proved to be the more effective treatment: Of 55 patients receiving HSCT, only three patients showed disease progression at one year, the study showed. Yet, 34 of 55 patients in the disease-modifying therapy group showed disease progression at one year. Disease progression was measured using the Expanded Disability Status Scale, a method for monitoring changes in symptoms over time.

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Among the HSCT group, the proportion of patients with disease progression was (roughly) 2% up to two years, 5% at three years, and 10% at 4 and 5 years. Meanwhile, the proportion of patients with no evidence of disease — defined as no progression, no relapses, and no new or enlarging lesions on MRI scans — was (nearly) 98% at one year, 93% at two years, 90% at three years, and 78% at four and five years.

By contrast, almost one quarter of the patients in the disease-modifying therapy group showed disease progression at one year, more than half at two years, and just under three-quarters at five years. And the proportion of patients with no evidence of disease was (about) 40% at six months, 21% at one year and 3% by years four and five.

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What are the side effects of HSCT?

Side effects of HSCT can include infertility, said Burt, who noted that women can choose to preserve their eggs before treatment. And some patients developed autoimmune thyroid disease, a treatable condition. He noted that the disease-modifying treatments also have side effects.

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Australian AHSCT Trial Results Released.

– The results of an observational study of 35 people with relapsing-remitting and secondary progressive MS who received the treatment in Sydney have just been released.

– Autologous haematopoietic stem cell therapy (AHSCT) uses a combination of chemotherapy and reinfusion of blood stem cells to rebuild and reset the immune system.

– In this study, 60% showed no evidence of disease activity for three years after the treatment and 13 participants showed improvements in their disability scores. 8 people had continued disability progression during the follow-up period.

– Immune cell analysis showed that after one year, attacking immune cells were still wiped out by AHSCT but cells that regulate the immune system were restored.


A Sydney team have published results from their study of Autologous Haematopoietic Stem Cell Therapy (AHSCT) in people with relapsing-remitting and secondary progressive MS.

AHSCT has been under investigation, worldwide and in Australia, as a treatment option for MS using different protocols and in different types of MS. Good results have been seen for many people with relapsing MS however, it is also a treatment with high risks and international clinical trials and studies have shown that it is not effective or suitable for everyone with MS.

AHSCT aims to reset the immune system using chemotherapy to wipe out most or all the immune cells and then the individual’s own blood stem cells are reinfused to rebuild the immune system. The hope is that the treatment puts MS into remission.

Researchers and clinicians at St Vincent’s Hospital in Sydney have been conducting a study of the treatment since 2010. Their results have been published in the Journal of Neurology, Neurosurgery and Psychiatry. The study included 20 people with relapsing-remitting MS and 15 people with secondary progressive MS, who have now been followed for an average of 3 years following the treatment.

This study used the “BEAM” chemotherapy protocol, which completely removes the immune system and is the one most commonly used in people with MS around the world, but with limited published clinical trial results.

Participants in this study had levels of disability that ranged from low to moderately severe (disability scores between 2 and 7 as measured by the expanded disability status score (EDSS)) and had failed to respond to at least two previous therapies for MS, including two thirds who had failed on natalizumab, a high potency MS medication.

The researchers tracked evidence of disease activity via relapses, brain lesions on magnetic resonance imaging (MRI) and disability progression. In this group of people with MS, 60% showed no evidence of disease activity for up to three years after the treatment. In the people with relapsing-remitting MS, the result was higher, with 70% showing no disease activity. 73% of participants had no disability progression during the follow-up period. In fact, 13 participants had improvements in their EDSS disability score of an average of 1.4 points – all but one of these had relapsing-remitting MS. However, eight participants had their disease continue to progress during the follow-up period, two with relapsing-remitting MS and six with secondary progressive MS.

83% of participants had no new or enlarging lesions at their last MRI scan and 96% showed no active lesions.

Participants experienced the expected side effects of high dose chemotherapy, including ulcers in the digestive tract, nausea and hair loss. One third required red blood cell transfusions and a half required platelet transfusions during their hospital stay. No-one died as a result of the treatment in this study which is in keeping with recent international AHSCT outcomes for people with MS receiving medium intensity chemotherapy where the treatment is provided at an experienced hospital centre

An important part of this study was the work conducted by MS Research Australia-funded PhD Student and clinician, Dr Jennifer Massey, who looked at the profile of immune cells in patients following the treatment. This work showed that the attacking types of T immune cell were still wiped out and that there was a sustained rise in other immune cells that work to calm and regulate the immune system. By comparison, these changes were not seen in patients who received the same AHSCT for lymphoma. This suggests that in people with MS, AHSCT may work by turning off the attacks as well as restoring the immune system’s ability to regulate itself. These results may help us work out how to better treat MS without needing to use intensive chemotherapy treatments.

This study shows that AHSCT can provide good outcomes for people with relapsing MS who do not respond to other types of MS treatments. The results are similar to those seen in other international studies and confirm that people with relapsing-remitting MS respond better to AHSCT than those with secondary progressive MS.

Each person’s situation is unique and decisions about any MS treatments, taking into consideration the potential benefits, risks and side effects, should be made in careful consultation with your medical team. A small number of Australian hospitals are currently providing this treatment for people with MS, but can only do so for patients who have failed to respond to other MS therapies and with a referral from a neurologist.

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Stem Cell Transplant Enabled This Wheelchair-bound MS Patient To Walk Again

 

A small, preliminary study in JAMA has found that hematopoetic stem cell transplant (HSCT) may be more effective than disease modifying drugs in patients with highly active relapsing-remitting multiple sclerosis (MS).1 The study is the first randomized trial of HSCT in relapsing-remitting MS. Findings were published online on January 15, 2019 in JAMA.

Roy Palmer, 49, was confined to a wheelchair for several years. He was an MS patient and suffered from multiple sclerosis many years ago due to which he couldn’t walk again. When the radical stem cell treatment emerged, he decided to give it a shot. Palmer went through a hematopoietic stem cell transplant (HSCT) after seeing a documentary about it on a program called Panorama on BBC. He said in an interview, “If they can have that done, on a trial, why can’t I have it done?” HSCT is performed by taking a patient’s own stem cells and destroying the immune system with radiation or chemotherapy. After performing all these steps, hematopoietic stem cells are transplanted back into the body.

The National Multiple Sclerosis Society has listed the treatment as risky and is still in the experimental stages. The procedure is yet to be approved by the Food and Drug Administration. The long-term side effects of the procedure include infections and infertility in both genders. Palmer decided to take the risks as they were worth a shot. He said that two days after the surgery he regained the feeling in both his legs and learned how to walk again. He said, “I’ve been given a second chance at life and I started volunteering at my local police station. We went on holiday not so long ago to Turkey and I walked on the beach. Little things like that, people do not realize what it means to me.”

Multiple sclerosis cripples millions of patients all over the world. It is also known as MS. The disease tricks the body to attack the protective coverings of nerves. This causes extensive damage to the spinal cord and the brain. Often the mobility of patient degrades from walking to vision loss, paralysis, and reduced brain functions. The issue is that the treatment of the disease has not been discovered yet. The Mayo Clinic says, “We went on holiday not so long ago to Turkey and I walked on the beach. Little things like that, people do not realize what it means to me.”

It is currently treated with corticosteroids like oral prednisone or with plasma exchanges if the steroids are not working on the patient. The disease was first highlighted in 2015 when a team from Chicago’s Northwestern Memorial Hospital performed first HSCT for an MS patient. The success of the treatment brought hope into the research for a cure to MS. HSCT is a life-saving treatment as well as cost effective. Most estimates show that MSCT treatments cost around $125,000. The FDA-approved drug for the treatment of MS cost around $5000 per month. MS patients are treated with one or more of those drugs.

The researchers from Northwestern Memorial Hospital has also advised MS patients that MSCT is not for everyone. Dr. Richard Burt explained, “If you’re doing well on first-line therapies, interferons or Copaxone, good, that’s where you should stay. But if you’re having frequent relapses, two or more a year despite those therapies … I think that’s the group that, rather than going to Tysabri or Fingolimod, should be given this therapy because it’s so much more beneficial. Plus, if you wait until you’ve had all those other [DMTs] then you increase the risk of this treatment.”

However, Palmer has huge gratitude for the procedure. In an August opinion piece, raising money for the Imperial Healthy Charity’s Blood Fund he wrote, “It might not be a cure for my MS, but this stem cell transplant has changed my life. I’m now able to walk unaided again. It can still be very painful, so I’m continuing to have physiotherapy to strengthen my legs. Some of the exercises are really hard but I’m hoping it improves.”

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bbbs-panorama-programme

Cancer treatment for MS patients gives ‘remarkable’ results

UK doctors in Sheffield say patients with multiple sclerosis are showing “remarkable” improvements after receiving a treatment usually used for cancer.

About 20 patients have received bone marrow transplants using their own stem cells. Some patients who were paralysed have been able to walk again. Prof Basil Sharrack, of Sheffield’s Royal Hallamshire Hospital, said: “To have a treatment which can potentially reverse disability is really a major achievement.” Around 100,000 people in the UK have MS, an incurable neurological condition. Most patients are diagnosed in their 20s and 30s. The disease causes the immune system to attack the lining of nerves in the brain and spinal cord.

Immune system ‘rebooted’

The treatment – known as an autologous haematopoietic stem cell transplant (HSCT) – aims to destroy the faulty immune system using chemotherapy. It is then rebuilt with stem cells harvested from the patient’s own blood. These cells are at such an early stage they’ve not developed the flaws that trigger MS. Prof John Snowden, consultant haematologist at Royal Hallamshire Hospital, said: “The immune system is being reset or rebooted back to a time point before it caused MS.” About 20 MS patients have been treated in Sheffield in the past three years. Prof Snowden added: “It’s clear we have made a big impact on patients’ lives, which is gratifying.”

Multiple Sclerosis

In MS the protective layer surrounding nerve fibres in the brain and spinal cord – known as myelin – becomes damaged. The immune system mistakenly attacks the myelin, causing scarring or sclerosis. The damaged myelin disrupts the nerve signals – rather like the short circuit caused by a frayed electrical cable. If the process of inflammation and scarring is not treated then eventually the condition can cause permanent neurodegeneration.

The BBC’s Panorama programme was given exclusive access to several patients who have undergone the stem cell transplant. Steven Storey was diagnosed with MS in 2013 and, within a year, went from being an able-bodied athlete to needing a wheelchair and losing sensation in much of his body. BBC’s panoramn programmeHe said: “I went from running marathons to needing 24-hour acute care. At one point I couldn’t even hold a spoon and feed myself.” Within a few days of the transplant he was able to move his toes, and after four months he could stand unaided. Steven still needs a wheelchair but is astounded at his progress: “It’s been incredible. I was in a dire place, but now I can swim and cycle and I am determined to walk.” Holly Drewry was just 21 when she was diagnosed with MS and her condition deteriorated after she gave birth to her daughter Isla.

She said “Within a couple of months I got worse and worse. I couldn’t dress or wash myself; I didn’t even have the strength to carry my daughter.” Holly needed a wheelchair before her transplant, but after the treatment she walked out of hospital. She said: “It’s been a miracle. I got my life and my independence back and the future is bright again in terms of being a mum and doing everything with Isla.” Two years on she has suffered no relapses and there is no evidence of active disease on her scans. Doctors describe her MS as dormant, but there is hope that the transplant might be a permanent fix.

Cost-Effective

United statesThe Royal Hallamshire Hospital – together with hospitals in the United States, Sweden and Brazil – is part of an international trial, MIST, which is assessing the long-term benefits of the stem cell transplant. All those on the trial have relapsing remitting MS, where patients experience attacks – or relapses – followed by periods of remission. The treatment involves intensive chemotherapy, so patients are warned that there are side-effects such as nausea and hair loss. Paul Kirkham, another MS patient, said he was glad to have had the transplant but added: “It does knock you. I’d rather have done 10 rounds with Mike Tyson.” The transplant involves a one-off cost of around £30,000, which is comparable to the yearly cost of some MS treatments.

Because the procedure involves no new and instead re-purposes an existing therapy using the patient’s own cells, there is little profit incentive for companies to get involved. Prof Richard Burt, Northwestern University, Chicago carried out the first HSCT for MS as long ago as 1995 and is coordinating the international trial which began in 2006. He said: “There has been resistance to this in the pharma and academic world. This is not a technology you can patent and we have achieved this without industry backing.” A study published last year involving MS patients in Chicago showed significant reductions in neurological disability, and for some the improvements persisted for at least four years, although there was no comparative control group.

The outcome of the more detailed MIST trial – which will report in a couple of years – could determine whether the stem cell transplant becomes a standard NHS treatment for many MS patients. Dr Emma Gray, head of clinical trials at UK’s MS Society , said: “Ongoing research suggests stem cell treatments such as HSCT could offer hope, and it’s clear that in the cases highlighted by Panorama they’ve had a life-changing impact. “However, trials have found that while HSCT may be able to stabilise or improve disability in some people with MS it may not be effective for all types of the condition.” Dr Gray said people should be aware it was an “aggressive treatment that comes with significant risks”, but called for more research into HSCT so there could be greater understanding of its safety and long term effectiveness.

Panorama is broadcast on BBC One at 20:30 on Monday 18 January 2016.…

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Intense Stem Cell Therapy Shows Promise as MS Treatment

A therapy known as HSCT performed well in a clinical trial, but experts caution the treatment might not be for everybody.

HSCT IndiaStem cells may be an important pathway for the successful treatment of multiple sclerosis, although it can be a long and painful road getting there.

A recent clinical trial bore this out

In the trial, people with multiple sclerosis (MS) using nonmyeloablative hematopoietic stem cell transplantation (HSCT) performed better than those on disease-modifying treatments (DMTs).

The randomized clinical trial is the first to compare HSCT to DMTs.

Researchers said a significant number of patients on HSCT treatment were able to slow disease progression, compared to those using DMTs.

Of the 103 participants, only three of those on HSCT saw disease progression compared to 34 of those on DMTs.

The research team concluded that HSCT slows progression better than DMT, but they added it is imperative to find the right type of patient to undergo what is a rigorous and sometimes dangerous therapy.

The study was led by Dr. Richard Burt, chief of immunotherapy and autoimmune diseases at the Northwestern Feinberg School of Medicine in Illinois.

“This important study is the first randomized trial of HSCT vs. DMT, and demonstrated that HSCT was superior to conventional DMT in stabilizing persons with relapsing MS with respect to relapses and progression and improving some functions,” said Dr. Barbara Giesser, professor of clinical neurology at the David Geffen School of Medicine at the University of California Los Angeles (UCLA) and clinical director of the UCLA MS program.

An intense treatment

HSCT uses chemotherapy to help cells “forget” they have MS.

In doing so, the immune system is stripped down to vulnerable levels. Patients must be hospitalized and treated with extreme care.

“HSCT is not one therapy but a range of therapies from a more mild type of chemo to a stronger type,” Bruce Bebo, PhD, executive vice president of research at the National Multiple Sclerosis Society, told Healthline. “Dr. Burt practices a more mild form of chemotherapy — more mild form of immunosuppression — so the risks are lower.”

Trial participants had relapsing MS with mild to moderate disabilities, ranging from 2 to 6 on the Expanded Disability Status Scale (EDSS).

“This study stands above the others — first controlled randomized autologous stem cell transplant. Burt and his team should be applauded for taking this on. It’s what everyone was asking for,” Bebo said.

“A lot of groups are experimenting with this type of treatment — case studies and evidence is accumulating for its positive benefit and accumulating info for the best patient and approach for success,” he added.

Bebo explained how difficult this study was to perform and how Burt and his team created an unbiased way to compare HSCT to DMTs, excluding ocrelizumab and alemtuzumab, which were not included.

Due to potential visible side effects with the chemo such as hair loss, a “blind reader” reviewed the results of the tests during the trial. This reader was off site and had no access to the participants.

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Greater Benefits for Relapsing-Remitting MS Found with HSCT Therapy

 

Nonmyeloablative hematopoietic stem cell transplantation (HSCT) was associated with prolonged time to disease progression when compared to disease-modifying therapies (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS), according to results published in Journal of the American Medical Association (JAMA).

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Nonmyeloablative hematopoietic stem cell transplantation (HSCT) was associated with prolonged time to disease progression when compared to disease-modifying therapies (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS), according to results published in Journal of the American Medical Association (JAMA).

HSCT IndiaIn a randomized controlled trial, participants who met inclusion criteria for the trial (N=110) were randomized into the HSCT group (n=55) and continuation of DMT group (n=55). There were no significant differences between the HSCT and DMT groups in terms of sex, age, baseline expanded disability status scale (EDSS) scores, number of gadolinium-enhancing lesions, T2-weighted lesion volume on MRI before randomization, number of prior DMTs, or type of prior DMT or immune treatments.

Participants in the DMT group received a DMT of higher efficacy or a different class than the therapy taken at the time of randomization (based on decision of their treating neurologist). For patients in the HSCT group, DMT use was discontinued, followed by variable washout periods before admission for HSCT.

Peripheral blood stem cells were collected 10 days after intravenous cyclophosphamide (2 g/m2) and 5 to 10 μg/kg per day of subcutaneous filgrastim beginning 5 days after cyclophosphamide. The immune ablative regimen was intravenous cyclophosphamide, 50 mg/kg per day on days −5 to day −2 before stem cell infusion (day 0) and rabbit antithymocyte globulin, .5 mg/kg on day −5, 1 mg/kg on day −4, and 1.5 mg/kg on days −3, −2, and −1. Blood products were irradiated, cytomegalovirus safe, and leukocyte depleted. Filgrastim (5-10 μg/kg per day) was started on day +4 and continued until engraftment.

The primary endpoint, defined as an increase in disease progression (EDSS score increase of ≥1) of at least 1 point on 2 evaluations 6 months apart after at least 1 year of treatment, occurred in 3 patients in the HSCT group and 34 patients in the DMT group, with a median follow-up of 2 years. The proportion of patients in the HSCT group with disease progression was 1.92% (95% confidence interval [CI], .27%-12.9%) at 1 year and 2 years, 5.19% (95% CI, 1.26%- 20.1%) at 3 years, and 9.71% (95% CI, 3%-28.8%) at 4 and 5 years.

The proportion of patients in the DMT group with disease progression was 24.5% (95% CI, 14.7%-39.1%) at 1 year, 54.5% (95% CI, 40.7%-69.4%) at 2 years, 62.5% (95% CI,48.3%- 76.7%) at 3 years, 71.2% (95% CI, 56.8%-84.2%) at 4 years, and 75.3% (95% CI, 60.4%-87.8%) at 5 years.

Mean EDSS score decreased (improved) in the HSCT group, from a pre-HSCT score of 3.38 to 2.36 at 1 year (mean change, −1.02 points), while the mean EDSS score increased (worsened) in the DMT group, from 3.31 to 3.98 at 1 year (mean change, +.67 points). The difference between the HSCT group and DMT group in the change in EDSS scores from baseline to 1 year was −1.7 (95% CI, −2.03 to −1.29; P <.001).

Notably, there was significant improvement in EDSS scores, NRS scores, and T2-weighted lesion volume percentages in the 31 patients who crossed over from the DMT group to receive HCST, suggesting that current definitions of progression for RRMS may not accurately assess irreversible disease progression for all patients.

Investigators noted this study was limited by its small sample size and the limited ability to collect follow-up data for patients receiving DMT and to assess longer-term secondary outcomes due to a study design that allowed patients in the DMT group in whom that treatment failed to cross over to receive HSCT.

HSCT is designed to eliminate autoreactive lymphocytes and “reboot” the immune system in a non-inflammatory environment. In an observational study of long-term disability outcomes of patients with relapsing and progressive forms of MS, researchers found that nearly half of these patients were free of neurological progression 5 years after receiving autologous HSCT1. Better outcomes were associated with younger age, relapsing form of MS, fewer prior immunotherapies, and lower EDSS score at baseline.

“We think what happens in HSCT is that the immune response is exposed to myelin in the absence of the danger signal,” Richard K. Burt, MD, principle investigator and chief, division of immunotherapy at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois, said in an interview with the National MS Society. “What we’re doing is stopping inflammation you need to treat when the disease in its inflammatory stage.”

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