Chemotherapy and self hematopoeitic stem cell transplant

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Chemotherapy and self hematopoeitic stem cell transplant

Postby rc_boro » Sat Oct 28, 2006 8:16 pm

I read somewhere within the last year of a study using high dose immuosuppresive therapy and self hematopoeitic stem cell transplanst. The results over 5 years was quite impressive. I believe the study was done in Europe and involved 18 pts. I believe the results showed out of those 18 post 5 yrs only one exacerbation out of the whole lot. Does anyone recall such a study? I might be off on some of the numbers since it is from memory.

I was searching around and found a chemo/hematopoeitic stem cell transplant study going on in Washington state. Is anyone here in that study? My MS specialist and I aren't very happy with my current state and will possibly be looking at significant changes i.e. Tysabri or chemo soon. If the need is there I was thinking of recommending this study instead of the above named therapies. If anyone has any info on this therapy I would greatly appreciate it.

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Postby bromley » Sun Oct 29, 2006 2:45 am


There are a number of chemo drugs that are being used / trialled. Mitoxantrone (Novantrone) is a licenced tretment for MS - see separate section on this site for individuals' experiences.

Campath and Rituximab are both cancer drugs and in trial (not yet licenced).

Here is a link to recent research on Cyclophosphamide.

HSCT is being used across different countries. There is also Bone Marrow Transplantation which is being trialled in nCanada (google Dr Freedman).

These are higher risk treatments but are used for a worsening disease course when other treatments have not been effective.

The positive is that they have been around for a while so the safety profile is known / safety monitoring mechanisms have been developed.

Best of luck

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Postby dignan » Sun Oct 29, 2006 12:13 pm


I don't know if I've found anything you didn't already know, and I'm not sure if the abstracts from Pubmed below refer to the study in which you are interested. The first 2 abstracts are from Italian studies (not sure if they refer to different studies or not). The next 2 are from Chinese studies. The last one is a review of autologous stem cell studies that shows an encouraging lack of fatalities over the last 3 years. Thought I'd throw it in there as it seems that though the procedure is still risky, they have made good progress on minimizing the risk.

Intense immunosuppression followed by autologous stem cell transplantation in severe multiple sclerosis.

Neurol Sci. 2005 Dec;26 Suppl 4:S200-3
Capello E, Saccardi R, Murialdo A, Gualandi F, Pagliai F, Bacigalupo A, Marmont A, Uccelli A, Inglese M, Bruzzi P, Sormani MP, Cocco E, Meucci G, Massacesi L, Bertolotto A, Lugaresi A, Merelli E, Solari A, Filippi M, Mancardi GL; Italian GITMO-Neuro Intergroup on ASCT for Multiple Sclerosis.
Department of Neurological Sciences Ophthalmology and Genetics, University of Genoa, Via De' Toni 5, I-16132, Genoa, Italy.

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.

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Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life.

Blood. 2005 Mar 15;105(6):2601-7. Epub 2004 Nov 16.
Saccardi R, Mancardi GL, Solari A, Bosi A, Bruzzi P, Di Bartolomeo P, Donelli A, Filippi M, Guerrasio A, Gualandi F, La Nasa G, Murialdo A, Pagliai F, Papineschi F, Scappini B, Marmont AM.
Bone Marrow Transplantation Unit, Careggi Hospital, University of Florence, Italy.

Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement.

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Autologous peripheral blood stem cell transplantation for severe multiple sclerosis.

Int J Hematol. 2006 Oct;84(3):276-81.
Su L, Xu J, Ji BX, Wan SG, Lu CY, Dong HQ, Yu YY, Lu DP.
Department of Hematology, XuanWu Hospital, Capital University of Medical Sciences, Beijing, P. R. China.

We describe the results of a clinical trial to evaluate the feasibility and toxicity of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with progressive multiple sclerosis (MS). Fifteen patients (all patients with secondary progressive MS) were enrolled. The median expanded disability status scale (EDSS) score at baseline was 6.0 (range, 4.5-7.5). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. In 9 patients, CD34+ cell selection was performed with a CliniMACS cell selection system, and 6 patients accepted infusion of unmodified peripheral blood stem cells. The modified BEAM (carmustine, teniposide, cytarabine, and melphalan) was the sole conditioning regimen used. The adverse effects included infections, mucositis, transient hepatotoxicity, and diarrhea. Three patients had flares of neurologic deterioration during mobilization, 8 patients had the same manifestation during transplantation, and 2 patients had similar flares within 3 months of transplantation. Six patients experienced continuous neurologic improvement after transplantation, 5 patients experienced neurologic progression, and 4 patients had stabilization of their disease. The confirmed progression-free rate was 63.8% at 49 months. The results of lymphocyte purging were no better than for no purging. Auto-HSCT proved to be safe and beneficial for some MS patients. Further studies are needed to establish the merit of this procedure for MS patients.

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Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients.

Clin Transplant. 2006 Jul-Aug;20(4):485-9.
Ni XS, Ouyang J, Zhu WH, Wang C, Chen B.
Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

OBJECTIVE: To observe the efficacy and toxicity of autologous hematopoietic stem cell transplantation (HSCT) in progressive multiple sclerosis (PMS). METHODOLOGY: Twenty-one patients with PMS were treated with autologous HSCT. Stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. After conditioning regimen of CY and total body irradiation or BEAM, stem cells were reinfused. CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion. The probabilities of confirmed progression-free survival and disease activity-free survival were used to assess the efficacy and the adverse experiences were recorded to detect the toxicities. RESULTS: The median follow-up time was 42 (6-65) months. The probabilities of confirmed progression-free survival and the disease activity-free survival were 75% and 33.3%, respectively. The principal adverse events included allergy, infection, elevation of liver enzymes, transient neurologic deterioration and depression. Two patients died of severe pneumonia and varicella-zoster virus hepatitis, at 4.5 and 15 months post-transplant, respectively. CONCLUSIONS: Autologous HSCT seems beneficial to PMS. However, more patients and longer follow up would be required to assess the risk/benefit ratio.

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Adult stem cells in the treatment of autoimmune diseases.

Rheumatology (Oxford). 2006 Oct;45(10):1187-93. Epub 2006 Jun 15.
van Laar JM, Tyndall A.
Department of Rheumatology, University of Basel, Felix Platter Spital, Burgfelderstrasse 101, Basel 4012, Switzerland.

During the past 10 yrs, over 700 patients suffering from severe autoimmune disease (AD) have received an autologous haematopoietic stem cell transplant as treatment of their disorder with durable remission being obtained in around one-third. The most commonly transplanted ADs have been systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. A fewer number of patients have received an allogeneic transplant. The initially reported overall treatment-related mortality of 7% has since fallen, with no further cases being reported in systemic sclerosis or multiple sclerosis in the past 3 yrs. This is thought to be due to more careful patient selection.The phase I/II data has led to currently running prospective randomised trials in systemic sclerosis, multiple sclerosis and systemic lupus erythematosus in Europe and North America. Immune reconstitution data suggests a 'resetting' of autoimmunity in those patients achieving stable remission, rather than simply prolonged immunosuppression. Recent results from in vitro experiments, animal models and early human experience in severe acute graft vs host disease suggest that multipotent mesenchymal stromal cells obtained from the bone marrow and expanded ex vivo, may exert a clinically useful immunomodulatory effect. Such cells are immune privileged and apparently of low toxicity. Further characterization of these cells and consideration of their possible clinical application in AD is underway.

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