Marrow and More

Once considered a desperate Hail Mary pass at the end of a losing battle against an incurable disease, bone marrow transplantation has become an integral part of the treatment plan for many children and adults with leukemia and other blood disorders.

Newer agents and drug combinations, new capability to detect the need for earlier transplants, new sources of blood stem cells, better donor matching and improved supportive care have contributed to improved outcomes for people diagnosed with blood cancers, said George B. Selby, MD, professor of medicine, director of the OU Blood and Marrow Transplant Program and holder of the Gary McKinney Chair of Bone Marrow Diseases. 

Since the first successful use of bone marrow stem cells in 1968 in Seattle by a pioneering team that included Robert Epstein, MD, OU emeritus professor of oncology-hematology, this relatively recent procedure saves thousands of lives every year. 

Epstein joined the OU faculty in 1981, "and we did the first transplant here in 1982," said Selby , who has been involved with the bone marrow transplant program since it began.  Since then, the OU program has performed more than 2,000 transplants for both adults and children. 

As the state's only comprehensive bone marrow and peripheral blood stem cell transplant program, it offers OU Cancer Institute patients a complete palette of options:

  • Autologous transplantation of the patient's own cells.
  • Allogeneic transplants of cells from siblings
  • Allogeneic transplants of cells from unrelated donors
  • Umbilical cord blood transplants
  • Transplantation in children, a program Selby established in 1993, is directed by Laura Rooms, MD

Healthy stem cells from bone marrow, peripheral blood or umbilical cord blood give patients a new immune system by replacing the damaged or destroyed marrow in adults who have acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CM)< Hodgkin's Disease or lymphomas and in children who have ALL, AML, Hodgkin's Disease, lymphomas or other diseases, such as aplastic anemia and neuroblastoma.

"When we first started, the only stem cell source we used was bone marrow," Selby said.  "The donor had general anesthesia, and we removed marrow from the pelvis."

It then became possible to collect the same blood-forming stem cells from a blood donor without using anesthesia and without poking a hole in the pelvis.  Although use of peripheral blood stem cells is a widespread transplantation practice, the OU program tends to prefer bone marrow because of a difference in the rate of graft-versus-host disease, Selby said.

The next big development in blood stem cell transplantation was the use of umbilical cord blood as the source.  Cord blood is used more for children than for adults since its small volume, about the amount of a soft drink can, contains a limited quantity of stem cells.

Two cord blood units may be required for an adult recipient, with the result that blood stem cells from three people intermingle: those remaining from the patient and those from two different donors.  "Eventually, one of the two cords becomes dominant.  When you look at the blood months later, all of the blood will be that of one donor."  How this happens is a mystery, Selby said.

Whether the transplantation process uses donor cells from bone marrow, peripheral blood or umbilical cord blood, the transfer of an immune system into a different person requires the use of immunosuppressive drugs until the transplanted immune cells decide to tolerate their new body rather than attack it.  This attack process, graft-versus-host disease, continues to be the bane of transplantation despite newer immunosuppressive drugs and more sophisticated, DNA-based testing of potential donor cells that have improved the odds of success significantly.

The first 100 days after a transplant are both critical and unpleasant for the patient.  "It's a very dangerous time," said Selby.  Immunosuppression begins immediately, as do transfusions, because chemotherapy and radiation have caused the patient's white and red cells and platelets to plummet.  The patient is shielded in isolation to protect from infections until the patient's new bone marrow begins to grow. 

Antibiotics are given, and those patients who develop mouth sores are fed intravenously.  Most feel weak and tired.  Patients are allowed to return home  when their white count reaches normal levels and they are again capable of self-care and can remain hydrated without intravenous fluids.

Having marrow and blood stem cell transplants available through the OU Cancer Institute "is a huge advantage for Oklahomans because most transplant centers make the patient stay in the town where the transplant is done for 90 to 100 days," should a problem arise, Selby said.

"So if they had to go to Houston or Seattle or Minnesota, not only does the patient have to go, but so does the caregiver.  Many patients are relatively young and have kids at home.  Who's going to take care of the kids?  Who's going to be working to keep the wolf from the door?  And where's the support system?  "But if they are Oklahomans and they come here, they can stay at home if they're within a two-hour drive to 100 miles."

Especially gratifying for Selby is the increased ability to know when a patient needs a transplant, which is ordinarily done when the patient is in remission.  With AML, for example, a patient's bone marrow will be checked for chromosomal mutations in OU Medicine's molecular biology labs.  Once the lab findings are received, "we can say that this patient will have a good prognosis with conventional chemotherapy, or we may see evidence that this patient will relapse immediately, so we get them a transplant as soon as possible."

Nonetheless, the national survival rate for AML is just 23.4 percent when all ages are considered but 60.2 percent for children under 15.  The news is much better for ALL, with a survival rate of 90.0 percent for children but less than 50 percent for adults.  The best results are with chronic myelogenous leukemia (CML) at 78.8 percent.

While CML is rare in children, they sometimes do develop it and may require a transplant, Selby said.  The first pediatric unrelated donor transplant at OUMC was performed for CML.  "There is nothing better than treating a little boy for late-stage CML and then getting to be the commencement speaker at his high school graduation," Selby said.