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LUPUS! Stem Cell Transplant Benefits Severe Lupus

Posted Jul 11 2010 12:00am

I can’t believe it! I was talking with not one, not 2, but 3 separate people yesterday about the treatment of Lupus and Severe Lupus.  I relayed some general information and this article from June 7th – http://repairstemcell.wordpress.com/2010/06/07/lupus-study-shows-promising-results-using-umbilical-cord-mesenchymal-stem-cells-scimitar-equity-blog/

My final point to each was: check back with me often, things change all the time…

So as I was swilling my coffee this morning and rubbing my eyes; what article do I see at the top of my reading list?

Stem Cell Transplant Benefits Severe Lupus!!

Wow, I can’t believe it!  SO…how much benefit was there?A little, a lot?

  • 12 patients fell to 3.2 from a baseline score of 12.1 and 4 of them showed “remarkable improvement” with scores of zero!!
  • All patients experienced a reduction in 24-hour proteinuria, which decreased significantly by one week from 2,538 mg to 1,430 mg (P<0.01).
  • 8 of 11 patients no longer had fatigue, weight loss, or low-grade fever, three months after transplantation.
  • 4 of 8 patients with cutaneous manifestations had their severe lesions healed completely.
  • 4 of 8 patients with cutaneous manifestations had their severe lesions healed partially.
  • Arthritis improved in four of six patients who had musculoskeletal involvement, serositis resolved in two, neurologic manifestations cleared in one, and refractory hypertension became controllable in five.
  • Antibody levels also fell, with serum titers of anti-double stranded DNA antibodies reaching a statistically significant difference from baseline at one and three months (P<0.05).
  • Two patients relapsed, one at six months and the other at 24 months.
  • No serious adverse events were seen during followup.

I’m so excited to share this information with my friends.  Enjoy everyone and when you finish reading below, you can lick here to read the technical data of the study. -dg

By Nancy Walsh, Staff Writer, MedPage Today
Published: July 29, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

Allogeneic mesenchymal stem cell transplantation resulted in improvements in disease activity, serologic markers, and renal function in patients with refractory systemic lupus erythematosus (SLE), a pilot study conducted in China found.

Twelve months after stem cell transplantation, scores on the SLE disease activity index among 12 patients fell to 3.2 from a baseline score of 12.1 (P<0.05), according to Jun Liang, MD, of Nanjing University, and colleagues.

Four of those patients showed “remarkable improvement” at one year, with scores of zero, the researchers reported online in the Annals of the Rheumatic Diseases.

Action Points <! –>


Some patients with refractory SLE remain symptomatic and at risk for progressive organ damage, including lupus nephritis, even with highly potent immunosuppressive regimens.

Hematopoietic stem cell transplantation has been tried in a few cases and led to some improvement, but was associated with mucositis, infections, and pulmonary injury.

Mesenchymal stem cells are less immunogenic then hematopoietic stem cells, because they lack the expression of costimulatory molecules and can escape alloantigen recognition.

Recent studies have suggested that mesenchymal stem cells from patients with SLE are defective in several ways, including their cytokine secretion, phenotype, growth, and immunomodulatory activities.

Liang and colleagues therefore hypothesized that SLE is a mesenchymal stem cell-mediated disease, and suggested that allogenic, rather than autologous, bone marrow mesenchymal stem cell transplantation might be an effective treatment.

So between March 2007 and November 2008 they enrolled 15 patients (14 women) with refractory disease along with healthy family member donors. The patients’ average age was 28.3 years, and average disease duration was 91.1 months.

Maintenance treatment one month after the transplantation included prednisone, 5 to 10 mg/day, and cyclophosphamide, 0.4 to 0.6 g every two to three months.

No other immunosuppressive medications were permitted unless a patient relapsed.

Mean follow-up was 17.2 months, and 13 of the patients had been followed for at least one year.

All patients experienced a reduction in 24-hour proteinuria, which decreased significantly by one week from 2,538 mg to 1,430 mg (P<0.01).

Among 11 patients who had longstanding fatigue, weight loss, or low-grade fever, eight no longer had these symptoms three months after transplantation.

Additionally, in eight patients who had cutaneous manifestations, severe lesions healed completely in four and at least partially in the other four.

Arthritis improved in four of six patients who had musculoskeletal involvement, serositis resolved in two, neurologic manifestations cleared in one, and refractory hypertension became controllable in five.

Antibody levels also fell, with serum titers of anti-double stranded DNA antibodies reaching a statistically significant difference from baseline at one and three months (P<0.05).

Two patients relapsed, one at six months and the other at 24 months.

No serious adverse events were seen during followup.

Possible mechanisms by which allogeneic mesenchymal stem cell transplantation might improve lupus include altering the cytokine profile toward a Th1 phenotype and expansion of regulatory T cells, which suppress the activity of autoreactive T cells, according to the researchers.

In this study, the effect of transplantation on regulatory T cells was assessed by flow cytometric analysis of the Foxp3+ CD4 T-cell subset, determining that the percentage of these cells increased to 4.58 from 2.56 (P<0.05) at baseline.

Another possible mechanism involves the ability of mesenchymal stem cells to differentiate into endothelial cells. Patients with lupus exhibit excessive endothelial cell apoptosis by serum IgG, and alterations in endothelial cells are thought to contribute to nephron damage.

“We hypothesize that, to some extent, differentiation of [mesenchymal stem cells] to endothelial cells reconstructs the structure of the nephron and improves renal function,” Liang and colleagues wrote.

However, they added, there are as yet no data to confirm or refute this hypothesis.

They noted that their follow-up was short, and that randomized trials will be needed to test this approach against more conventional therapies and to clarify clinical response criteria, post-transplant immunotherapy, and treatment of relapses.

The study was supported by the National Natural Science Foundation of China, Jiangsu Province Talent Foundation, and Jiangsu Province Natural Science Foundation.

No other disclosures were provided.

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