After a median follow-up of two years, the transplants successfully eliminated sickle cell disease in 11 of 17 patients. Three were fully matched to their donors and eight received half-matched donor marrow. All 11 patients are free of painful sickle cell crises and 10 no longer have anemia. There were no deaths and no unexpected toxicities.
Six of the 11 patients (all half-matched) have stopped taking immunosuppressive drugs, although some still require narcotics for chronic pain because of sickle cell-related organ damage. Blood tests on the six patients show that their red cells are now completely derived from their donor's marrow.
Patients with severe sickle cell disease (SCD) face shortened life spans, intractable pain and eventual organ damage as a result of their disease, an inherited disorder caused by a mistake in the oxygen-carrying hemoglobin molecules in red blood cells. The flawed genetic code stiffens red cells, and shapes them into a pronged "sickle" that clump and stick into blood vessel walls, cutting off blood and oxygen to tissues and organs throughout the body.
SCD occurs in approximately one in 400 African Americans, and rarely in Caucasians. An estimated 100,000 people are currently living with sickle cell disease in the U.S.
Most patients die before age 50, and many suffer poor quality of life with frequent episodes of "off-the-charts" pain, and an increased risk for kidney failure, stroke, deep-vein thrombosis, and lung disease.
Treatments include blood transfusions and a drug, hydroxyurea. Many patients use narcotics to control severe pain and have repeat hospitalizations. Bone marrow transplants have been successful in curing some cases, but matching donors are rare and the procedure itself poses risk.
In the current study, 17 patients at the Johns Hopkins Hospital were offered bone marrow transplant options, including the use of half-matched donor marrow to try and replace their "sickled" blood cells with new, healthy ones. The transplants were successful in 11 of the patients, of whom eight were only half-matches. Results of the trial were published in the Sept. 6 early online edition of Blood.
"We're trying to reformat the blood system and give patients new blood cells to replace the diseased ones, much like you would replace a computer's circuitry with an entirely new hard drive," says Robert Brodsky, M.D., director of the Division of Hematology at Johns Hopkins and The Johns Hopkins Family Professor of Medicine and Oncology. "While bone marrow transplants have long been known to cure sickle cell disease, only a small percentage of patients have fully matched, eligible donors."
National registries often are of little help in finding donors for sickle cell patients, because most of those in need are African American and other minorities who are vastly underrepresented in registries, say the Johns Hopkins researchers.
To overcome the shortage of donors, investigators at Johns Hopkins developed techniques, recently tested in leukemia and lymphoma patients, to transplant with bone marrow that is half-identical or "haploidentical" to the patient's tissue type. Half-matched bone marrow can be obtained from parents, children and most siblings, and is extracted by needle from the hip bone.
For the study, the Johns Hopkins team screened 19 patients to find bone marrow donors with either half-identical or fully matched tissue. Each transplant candidate had experienced many severe pain crises, significant organ problems, or had failed hydroxyruea, the only drug known to curtail sickle cell symptoms. The team found donors for 17 of the 19 patients: 14 were half-identical and three were fully matched siblings. The youngest patient was 15; the oldest 46.
Before each transplant, sickle cell patients received a "conditioning" regimen of low-dose immunosuppression drugs, low toxicity chemotherapy, and low-dose total body irradiation. Brodsky says this gentler approach to pre-transplant therapy has made transplant possible for sickle cell patients whose tissues and organs have been ravaged by the disease.
After the transplant, all patients received high doses of the chemotherapy drug cyclophosphamide, which kills remaining blood cells, including diseased sickled cells, and preserves the donor's stem cells responsible for making new, healthy cells.
Of the 17 patients, six transplants were not successful; however, because of the reduced intensity of the conditioning regimen, all of these patients recovered their own blood cells.
There were no deaths, some infections, and only slight skin-related graft versus host disease symptoms in one patient, which cleared without therapy, the researchers reported. Some brain swelling occurred in three patients during the conditioning period and resolved without neurologic damage.
The Johns Hopkins doctors say that while the majority of patients in the trial had successful transplants, about less than half did not.
"Sickle cell disease patients undergo multiple blood transfusions throughout their lives and may have acquired antibodies against many different blood types, making it more difficult than usual to give patients donated bone marrow." says Javier Bolaños-Meade, M.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center and principal investigator of the study.
Improving the rate of engraftment in haploidentical transplants for sickle cell disease remains a challenge, they say, but the researchers are looking for additional ways to overcome it, including increasing the number of stem cells transplanted and using other immunosuppressant drugs during the transplant.
In addition to Bolaños Meade and Brodsky, researchers contributing to the study included Ephraim Fuchs, M.D., Leo Luznik, M.D., Sophie Lanzkron, M.D., Christopher Gamper, M.D., Ph.D., and Richard Jones, M.D., at Johns Hopkins.
Funding for the research was provided by the National Cancer Institute and National Institutes of Health (P01CA15396 and K23HL083089) and Sistema Nacional de Investigadores (Mexico).
Fuchs, Luznik, Brodsky and Jones are listed as inventors on a patent application regarding the "use of high-dose, post-transplantation oxazaphosphorine drugs for reduction of transplant rejection." Lanzkron served in a scientific advisory board for Hemaquest.On the Web:
Richard Jones, M.D., discusses bone marrow transplants and haploidentical transplants: http://www.youtube.com/watch?v=c8s7mC_X_Zo&feature=share&list=PL60C509D56B1E0674
Vanessa Wasta | EurekAlert!
TSRI researchers develop new method to 'fingerprint' HIV
29.03.2017 | Scripps Research Institute
Periodic ventilation keeps more pollen out than tilted-open windows
29.03.2017 | Technische Universität München
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences