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Alternative to Marrow Transplant
Eases Donation, Recovery Time

By Josť Alvarado

On the Front Page...
(Second story in two-part series on obstacles and advances in bone marrow transplantation.)

An alternative procedure to traditional bone marrow transplantation may speed up blood cell recovery in leukemia and cancer patients, as well as save donors the trouble of going through surgery to extract marrow from the rear of the pelvic bone. Patients transplanted with peripheral blood stem cells (PBSCs) also begin producing infection-fighting white blood cells sooner, according to NIH studies.

Continued...

The National Marrow Donor Program views peripheral blood stem cell transplants as a new treatment option available for unrelated donors and patients. Currently, most PBSC transplants are autologous -- cells are removed from a patient, stored as the patient receives high-dose therapy, and reinfused into the same patient. In the setting of related-donor (sibling) transplants, PBSCs are gradually replacing marrow as the preferred source of transplant material. In settings where the recipient is unrelated to the donor, PBSC transplants are generally performed only when a second donation is needed to counter graft rejection, as the recipient's body rejects donated marrow; or when engraftment does not continue, that is, the transplanted stem cells simply fail to grow and produce new blood cells.

The use of unrelated-donor PBSC transplants was initially limited by the fear that the large number of lymphocytes present in PBSC collections would increase the incidence and severity of graft-versus-host disease, in which these lymphocytes identify the recipient's body as foreign and attack it. There was also concern that growth factors -- proteins used to stimulate development of blood cells from collected stem cells -- might promote circulation of tumor cells in cancer patients.

But the positive response of leukemia and cancer patients to autologous PBSC transplants, and their growing application, have led scientists to consider widening the use of PBSC transplants among unrelated donors and patients. According to NIH studies, whether a center uses autologous bone marrow, stem cells or both during transplant does not affect the cure rate for a disease. However, patients transplanted with peripheral blood stem cells begin producing infection-fighting white blood cells sooner, which reduces the period of time they are at risk of developing a serious infection. Based on preliminary results in related transplants, NMDP is conducting a study to evaluate unrelated PBSC transplants.

All blood cells develop from immature cells called stem cells. Most are found in the bone marrow, although some, called peripheral blood stem cells, circulate in blood vessels throughout the body. Stem cells can mature into red blood cells (which carry oxygen), white blood cells (which fight infections), and platelets (which help blood to clot).

In the October 1996 compilation of "Seminars in Hematology," Dr. Susan Leitman, head of the blood services section in the Clinical Center's department of transfusion medicine, and her colleague Dr. Elizabeth Read, examine the results of several studies of PBSC transplants. "The advantages of using peripheral blood rather than marrow as the source of a stem cell graft are numerous. In the autologous setting, these include (1) avoidance of anesthesia and physical discomfort and hospitalization required of marrow harvest; (2) harvesting stem cells even when the marrow is infiltrated with tumor, or is severely hypocellular due to fibrosis or irradiation; and (3) collection of a larger number of stem and progenitor cells because several blood volumes can be processed repeatedly, whereas marrow collection is limited to 1 to 2 liters."

Further, Leitman and Read state, "If the initially promising results of PBSC allografting continue to be realized, it is likely that primary transplants accomplished via the NMDP will also move away from marrow and toward blood as the hematopoietic source (to stimulate the development of blood cells)." They point out how PBSC transplants "have virtually replaced autologous marrow transplants in Europe; in England, greater than 90 percent of autologous hematopoietic grafts are currently derived from mobilized blood progenitor (stem) cells."

Jaime Oblitas, manager of the Marrow Donor Program in the department of transfusion medicine, estimates that, in the United States, PBSC transplants number around 500 to 600 per year, compared to 4,000 allogeneic bone marrow transplants per year.

As in bone marrow transplants, donors and patients who participate in PBSC transplants must have matching human leukocyte antigens (HLAs). HLAs are proteins found on the surface of white blood cells and other tissues that are used to match donor and patient. Whereas marrow transplants involve a surgical process to remove marrow from the interior of the pelvic bone, PBSC transplants are more akin to the hassle-free routine of blood donation.

The PBSC transplant procedure begins when the donor is injected with a growth factor, which causes stem cells to multiply and be released from the marrow into the blood stream. This is done because stem cells normally present in peripheral blood circulate in much lower concentrations than in marrow. The relatively small number of stem cells found in peripheral blood before the growth factor is given makes it difficult to collect enough cells for a successful transplant. The donor, therefore, is injected with the growth factor for 5 consecutive days. This may cause some side effects such as bone or muscle aches, headaches and fatigue.

Peripheral blood stem cells are harvested in a nonsurgical process called apheresis or leuka-pheresis. The procedure is similar to one used by blood centers to collect platelets, in which blood is removed from a large vein in one arm and is sent to a machine that separates out cells by centrifugal force. The remaining blood is returned through a tube to the other arm. Typically, apheresis takes about 3 to 4 hours to complete. Sometimes, stem cells can't be collected using the veins in the forearm, therefore a plastic tube called a central line is placed in the femoral vein, located in the groin area. NMDP literature says 1 in 6 PBSC donors require a central line.

In an NMDP survey of volunteer donors provided with information comparing marrow and PBSC donation, 59 percent say they would be open to considering a PBSC donation.

The Few, the Proud, the Ex-Navy Man

By Rich McManus

Richard Haddon of Woodbridge, Va., works for a company that burns trash to generate electric power, so he already knows about the advantages of recycling. For the second time in less than a year, he visited NIH recently to "recycle" his own stem cells -- they are helping cure a woman in Europe of chronic myelogenous leukemia.

Last April, he underwent surgery here to harvest stem cells from his bone marrow. He happens to share tissue type (human leukocyte antigens) with a woman overseas dying of leukemia. The woman now shows no trace of leukemia, but signs of rejection of Haddon's marrow are appearing, so she needs a reinfusion of the "good guy" cells that help build blood cells and reconstitute her immune system.

Dr. Susan Leitman, head of the blood services section in the CC's department of transfusion medicine, checks on Haddon during a 5-hour harvesting procedure.

Thanks to peripheral blood stem cell (PBSC) transplantation, Haddon can offer a "booster" dose of cells more painlessly than the initial operation. On Oct. 6, in a 5-hour procedure in the Clinical Center, Haddon contributed PBSCs that were hand-carried on a flight that evening to Europe. The recipient got them via infusion the following morning.

Just 8 months ago, Haddon would have been asked to undergo a second surgical harvest if the first one didn't "take." That was before the NIH Blood Bank adopted PBSC transplants for certain situations.

"This is the ideal situation in which to give blood-derived stem cells," said Dr. Susan Leitman, head of the blood services section in the department of transfusion medicine. "They engraft quicker, the donor doesn't need to go to the operating room again, and there's no anesthesia involved."

Haddon did have to take a 5-day course of a blood cell growth factor delivered via injection, to stimulate his circulating PBSCs. "This gives a 50- to 100-fold increase in PBSC's," explained Leitman. The factor has some minor side effects: "The worst part is the headache," said Haddon. "It's not like a normal one. It's more like a fog. There's also some achiness in my back and knees. You just feel 'off' while you're taking it." Patients typically recover within 24 hours of the harvest, noted Leitman. "With PBSC transplantation, the discomfort comes before you donate, whereas with marrow donation, the pain comes after," she said.

An ex-Navy man, Haddon brushed off the blahs. Compared to the benefits, it was clearly no big deal.


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