Adding irradiation before transplant improves long-term results and should change practice
Scleroderma with internal organ involvement is a debilitating and lethal autoimmune disorder with few effective treatments. But a study led by Duke Health researchers has found new cause for optimism using an aggressive stem cell transplant regimen.
The researchers, publishing in the Jan. 4 issue of the New England Journal of Medicine, found significantly improved survival among patients with a severe form of scleroderma who underwent chemotherapy, whole body radiation and a stem cell transplant. Patients also had less need for immune suppressant drugs after transplant.
“Scleroderma hardens the skin and connective tissues and in its severe form leads to fatal organ failure, most often the lungs” said lead author Keith Sullivan, M.D., James B. Wyngaarden Professor of Medicine and Cellular Therapy at Duke. “In these severe cases, conventional drug therapies are not very effective long-term, so new approaches are a priority.”
Earlier publications suggested that stem cell transplant might be a viable treatment, using less intensive treatment without irradiation. These studies showed that reduced-intensity stem cell transplant improved survival, but the disease often returned and patient safety remained a concern. As a result, conventional immunosuppressive drug treatment remained the standard of care in the U.S.
In the current study, Sullivan and colleagues developed a transplant conditioning regimen that included high-dose chemotherapy plus whole-body radiation to fully wipe out the patient’s defective immune-forming system, with the aim of improving survival and diminishing the effects of the disease. They limited radiation by shielding patients’ kidneys and lungs while repopulating the blood and immune system.
Thirty-six scleroderma patients were randomly assigned to receive transplant. The regimen was designed to destroy the patients’ defective autoreactive immune system and replace it with their own blood stem cells that had been removed and treated to eliminate self-reacting lymphocytes.
For comparison, 39 additional patients were randomized to receive 12 monthly intravenous injections of cyclophosphamide, a conventional immune suppressing treatment for severe scleroderma.
“These results show that individuals with poor-prognosis scleroderma can improve and live longer and that these advances appear durable.”
The study was conducted over a 10-year period at 26 universities in the United States and Canada. The primary study endpoint at 54 months was a global rank composite score based on a hierarchy of scleroderma features including survival, organ function, quality of life and skin hardening. Results showed significant benefit with transplant: 67 percent of 1,404 pairwise comparisons favored transplant vs. 33 percent favoring cyclophosphamide.
By study endpoint, fewer transplant recipients resumed use of anti-scleroderma drugs (9 percent vs. 44 percent of controls). Overall survival at 72 months was 86 percent after transplant vs. 51 percent after cyclophosphamide — a highly significant benefit.
“These results show that individuals with poor-prognosis scleroderma can improve and live longer and that these advances appear durable,” Sullivan said.
Treatment-related mortality at the study endpoint of 54 months was 3 percent among transplant recipients while cyclophosphamide recipients had no treatment-related deaths. In the short term, transplant recipients also had more serious side effects, such as low blood counts and infections.
“Patients and their doctors should carefully weigh the pros and cons of intensive treatment with stem cell transplant, but this may hopefully set a new standard in this otherwise devastating autoimmune disease,” Sullivan said. “These advances show the value of medical research and clinical trials in finding better therapies to advance health.”
The Latest on: Stem cell transplant
- Elk Grove Man Selling Memorabilia to Help Pay for Stem Cell Therapyon September 6, 2019 at 10:33 pm
ELK GROVE -- A few years ago, a young Elk Grove father turned to social media to fundraise for a family friend whose son needed a heart transplant ... the cost for stem cell therapy.
- A live-saving stem cell match has been found for a 7-year-old boyon September 6, 2019 at 5:23 am
Finley will receive his much needed transplant. But Jo is hopeful and said if all goes well Finley could lead a normal life. It comes after the family endlessly held stem cell donor drives in a bid to ...
- The Berlin Patient: Cured of HIV with a stem cell transplant, Timothy Brown visits Vancouveron September 5, 2019 at 5:12 pm
An anonymous stem cell donor cured Timothy Ray Brown of both his leukemia and his HIV. For years, experts wondered whether it was a cure or just a temporary remission. It’s been 11 years.
- Outcomes of allogeneic hematopoietic cell transplant for acute myeloid leukemia in adolescent patientson September 5, 2019 at 10:29 am
We studied the impact of disease type, remission status, ELN risk group, ABO mismatch, time from diagnosis to transplant, patient and donor age, conditioning type, stem cell source, and the year of ...
- Study Shows Stem Cells May Be Better Choice Than Tissue Transplantation for Treating LSCDon September 5, 2019 at 8:30 am
indicate that a limbal stem cell (LSC) transplantation is superior to a tissue graft in treating limbal stem cell deficiency syndrome (LSCD). This could result in a new and better treatment for LSCD, ...
- Boy beats blood cancer with 2nd shot at stem cell transplant in Gujaraton September 2, 2019 at 7:37 pm
AHMEDABAD: Priyanshu Vasava,15, now has his father’s blood, cent percent! The boy — hailing from a tribal district of Narmada — was recently declared free of Hodgkin’s lymphoma, or blood ...
- Woman regains sight after stem cell transplanton August 30, 2019 at 11:52 pm
A patient who was almost blind in one eye has had her sight restored after undergoing the world’s first transplant of corneal tissue created from stem cells. The breakthrough by doctors at Osaka ...
- Pancreas on a chip: Organ-on-a-chip and stem-cell tech combinedon August 30, 2019 at 1:36 pm
But like all transplants, there is a lot involved in making sure that ... The device makes it easier to screen drugs that stimulate insulin secretion, test stem cell-derived beta cells, and study the ...
- How Stem Cell Therapy Saved One Man's Lifeon August 30, 2019 at 3:03 am
About eight years ago, he had been diagnosed with chronic kidney disease, but at the time of his diagnosis he was told that if he kept his weight down, he would never need a transplant ... Joseph ...
- 3-year-old Texas girl in urgent need of transplant after two attempts with family members failon August 29, 2019 at 2:51 pm
HOUSTON — A 3-year-old girl from Magnolia is fighting for her life in a Houston-area hospital, waiting desperately for a blood stem cell transplant to fight her rare and deadly blood disorder. Addyson ...
via Google News and Bing News