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School of Medicine
Leukemia, multiple myeloma and blood disorders
Physician-scientists at Johns Hopkins have developed a procedure called a half-matched bone marrow transplant that has been successful in “curing” patients of some cancers and blood disorders like sickle cell anemia. Rather than wiping out a patient’s immune system before transplanting donor bone marrow, doctors administer just enough chemotherapy to suppress the immune system, which keeps patients from rejecting the donated marrow without harming their organs. As a result, the side effects are much milder; only about half of patients may need to be admitted to the hospital. This procedure also greatly expands the potential donor pool, making more patients eligible for the transplant. Since developing the treatment more than a decade ago, Kimmel Cancer Center experts have performed more than 600 half-matched transplants for adult and pediatric leukemia and lymphoma. Johns Hopkins is currently the only center offering this type of transplantation for chronic leukemias, multiple myeloma and myeloproliferative disorders; other centers consider this treatment only for acute leukemias or lymphomas. Research results were reported in July 2011.
How it works
Three days after the transplant, a patient is given a high dose of a drug called cyclophosphamide, which “re-boots” the immune system. The cyclophosphamide spares the donor's stem cells and allows them to establish new blood cells and a new immune system. The budding immune system is re-trained to see the patient's body as friend, preventing the patient from rejecting the transplanted bone marrow. Doctors speculate the procedure works because with a higher level of mismatch between the donor and recipient, the immune system reacts more strongly against the cancer and lowers the chance of relapse, explains Dr. Ephraim Fuchs, associate professor of oncology, who helped develop the procedure.
Normally, doctors look for a donor who matches a patient's tissue type, specifically their human leukocyte antigen (HLA) tissue type. HLAs are proteins — or markers — found on most cells in the body. The immune system uses these markers to recognize cells that belong in the body versus those that do not. The closer the match between a patient's HLA markers and the donor’s, the better for the patient. In most cases of sickle cell disease, for example, doctors looked for a nearly full match prior to bone marrow transplantation. This was extremely difficult because in many cases, the person with the closest match, such as a sibling, may also have carried the sickle cell gene. The Hopkins procedure requires just a half-match, meaning that a patient’s parents or children could be suitable donors. With this option, doctors estimate that more than half of sickle cell patients, and nearly all patients with other blood cancers or autoimmune disorders, have potential matches.
Older age or match are not barriers
Kimmel Cancer Center researchers demonstrated that advanced age should no longer be a barrier to patients in need of bone marrow transplants. A study of 273 bone marrow transplants, in which a family member with partially-matched marrow was the donor, showed no difference in outcomes for patients aged 50 to 75, including graft-versus-host disease, mortality, and overall survival. As previously shown, the related haploidentical transplant did as well as matched donor transplants. These data demonstrate that bone marrow transplants are available to everyone in need regardless of match or age.
Johns Hopkins researchers are studying the use of half-matched transplants to improve the effectiveness and safety of solid organ transplants with living donors. Kimmel Cancer Center researchers are collaborating with transplant surgeons to begin a combined kidney/half-identical bone marrow transplant. If the research proves successful, the procedure could essentially eliminate organ rejection and a lifetime of antirejection drugs, since the patient and donor would have the same immune system.