Our tax dollars are at work and paying off in chances for new cures for a host of genetic diseases by using new less toxic and less fatal techniques to fix our immune systems.
Where is it happening? At a division of the National Institute of Health called the National Institute of Diabetes, Digestive and Kidney Disease
What is happening? The researchers at this institute and the Institutional Review Board had the courage to try a new kind of stem cell transplant that can cure without the patient's immune system being destroyed in its entirety. The patient/recipient's bone marrow is only partially destroyed to give room for HEALTHY donor cells to grow. The two bone marrows grow together as one in a process called mixed chimerism. The healthy part of the new bone marrow/immune and blood system cures the defective part of the patient's immune system.
The procedure written about below is being used in this case for a blood disorder, sickle cell anemia, but it could just as well be used for an autoimmune disease.
For most of us only need a few healthy immune cells to stop our disease.
In traditional therapies the bone marrow, the seat of the blood and immune system in a patient/recipient's body, is TOTALLY destroyed by radiation and/or drugs before donor blood and immune system cells are given to the patient/recipient. The donor cells can then have room in the now empty patient/recipient's bone marrow to reproduce and fully replace the destroyed immune system in the patient. Most of the time that happens, but not always.
Sometimes there is only
(1) partial replacement and the patient/recipient is left with a less than fully functioning immune system for the rest of their lives.
(2)Sometimes an infection appears in the patient/recipient before the immune system has time to fully regrow. The infection then often kills the patient/recipient.
(3)Sometimes GvHD starts a few years later after an apparently completely successful transplant. For unknown reasons the new immune system of the donor starts attacking the patient recipient's body. This horrible process is called Graft Versus host Disease or GvHD. The skin and mucous membranes of the patient/recipient are dissolved away by the donor's immune system. Overwhelming infection results, the patient often dies.
The lifetime success rate for full replacement of bone marrow and immune system is about 75% at best which is far better than zero chance for a cure. This full replacement procedure does work and is a life saver.
A teacher friend of mine contracted leukemia in the early 1990's and was given a full bone marrow/immune system replacement using her siblings bone marrow cells. That teacher is alive and well today. She would have died of the leukemia, more than 15 years ago without the full replacement of her bone marrow. In cancer full replacement is necessary to make sure all the cancer cells are gone.
In autoimmune diseases and blood disorders without cancer, only a relatively small number of healthy cells are needed.
While full replacement can work, researchers continue to look for better methods with higher life time success rates. This mini transplant protocol at NIDDK looks like a good one.
The idea of not completely destroying the patient's immune system has been used before with different drugs and amounts of radiation. Read about recent try with this technique at Johns Hopkins here:
If a best practices procedure can be found and codified, then many other hospital bone marrow centers might FINALLY have the courage to give it a try. I am hoping for someone at the UCLA or UCSD bone marrow transplant centers here in Southern California to have this kind of courage soon. I would like to see my youngest son walk and run again.
I especially hope they take note of the remarkable success of the Italian and Israeli teams of researchers in using massive infusions of donor T regs days before the donor's immune cells are given to the patient. Read more here:
Here is the article from NIDDK a division of our NIH paid for by our federal income tax dollars. Hooray for the federal government!
N Engl J Med. 2009 Dec 10;361(24):2309-17.
Allogeneic hematopoietic stem-cell transplantation for sickle cell disease.
Hsieh MM, Kang EM, Fitzhugh CD, Link MB, Bolan CD, Kurlander R, Childs RW, Rodgers GP, Powell JD, Tisdale JF.
Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
BACKGROUND: Myeloablative allogeneic hematopoietic stem-cell transplantation is curative in children with sickle cell disease, but in adults the procedure is unduly toxic. Graft rejection and graft-versus-host disease (GVHD) are additional barriers to its success. We performed nonmyeloablative stem-cell transplantation in adults with sickle cell disease.
METHODS: Ten adults (age range, 16 to 45 years) with severe sickle cell disease underwent nonmyeloablative transplantation with CD34+ peripheral-blood stem cells, mobilized by granulocyte colony-stimulating factor (G-CSF), which were obtained from HLA-matched siblings. The patients received 300 cGy of total-body irradiation plus alemtuzumab before transplantation, and sirolimus was administered afterward.
RESULTS: All 10 patients were alive at a median follow-up of 30 months after transplantation (range, 15 to 54). Nine patients had long-term, stable donor lymphohematopoietic engraftment at levels that sufficed to reverse the sickle cell disease phenotype. Mean (+/-SE) donor-recipient chimerism for T cells (CD3+) and myeloid cells (CD14+15+) was 53.3+/-8.6% and 83.3+/-10.3%, respectively, in the nine patients whose grafts were successful. Hemoglobin values before transplantation and at the last follow-up assessment were 9.0+/-0.3 and 12.6+/-0.5 g per deciliter, respectively. Serious adverse events included the narcotic-withdrawal syndrome and sirolimus-associated pneumonitis and arthralgia. Neither acute nor chronic GVHD developed in any patient.
CONCLUSIONS: A protocol for nonmyeloablative allogeneic hematopoietic stem-cell transplantation that includes total-body irradiation and treatment with alemtuzumab and sirolimus can achieve stable, mixed donor-recipient chimerism and reverse the sickle cell phenotype. (ClinicalTrials.gov number, NCT00061568.) 2009 Massachusetts Medical Society