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Pubmed Linki : http://www.docguide.com/bone-marrow-transplantation-shows-promise-adults-severe-sickle-cell-disease?tsid=5

Konu : Kemik İliği Nakli

Literatür İçeriği :  CHICAGO -- July 1, 2014 -- Use of a lower intensity bone marrow transplantation method shows promising results among 30 patients with severe sickle cell disease, according to a study published in the July 2 issue of JAMA.

Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but associated toxicity has made the procedure prohibitive for adults.

The development of nonmyeloablative conditioning regimens may facilitate safer application of allogeneic HSCT to eligible adults, according to Matthew M. Hsieh, MD, National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH), Bethesda, Maryland, and colleagues.

The researchers explored a nonmyeloablative approach in a pilot group of 10 adults with severe sickle cell disease, using a simplified HSCT regimen (with stem cell donation from a immunologically matched sibling) that had few toxic effects. All patients continued taking immunosuppression medication.

The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in patients with donor CD3 engraftment of >50% and normalisation of haemoglobin.

In the current report, the authors describe the outcomes for 20 additional patients with severe sickle cell disease, along with updated results from the first 10 patients. All 30 patients, aged 16 to 65 years, were enrolled in the study from July 2004 to October 2013.

As of October 25, 2013, 29 patients were alive with a median follow-up of 3.4 years, and 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease.

At 1 year, 25 patients (83%) had full donor-type haemoglobin and 15 engrafted patients discontinued immunosuppression medication and had no graft-vs-host disease.

The average annual hospitalisation rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant.

Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalised and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg 6 months after the transplant.

There were 38 serious adverse events including pain, infections, abdominal events, and toxic effects from the medication sirolimus.

“In this article, we extend our previous results and show that this HSCT procedure can be applied to older adults, even those with severe co-morbid conditions,” the authors wrote. “These data reinforce the low toxicity of this regimen, especially among patients with significant end-organ dysfunction.”

“In this series of patients who underwent a simplified HSCT regimen to date, reversal of sickle cell disease phenotype was achieved in the majority of patients,” the authors continued. “Engrafted patients continued to be disease-free and without graft-vs-host disease. Further accrual and follow-up is required to assess longer-term clinical outcomes, adverse events, and transplant tolerance.”

In an accompanying editorial, Allison A. King, MD, and John F. DiPersio, MD, Washington University School of Medicine, St. Louis, Missouri, wrote: “In a population of relatively older adults with sickle cell disease, these findings offer hope. Based on these exciting results, the role of age as a contraindication for offering adults with sickle cell disease and a matched sibling the chance of curative allogeneic stem cell transplant should be reconsidered.”

SOURCE: JAMA

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