Summer 2005

Pediatric Leukemia: BMT

A perennial, heartbreaking feature of pediatric oncology programs around the country is sick children who are candidates for bone marrow transplantation, but have no histocompatible, or tissue-matched, donors. Pleas go out for volunteer donors, but the truth is that time and the odds are stacked against patients and families. There is at best a 25 percent chance that a sibling will be compatible, and only a 1 percent chance that a parent will match. For most children without a matched relative, there is at best a 40 percent chance that a matched volunteer donor will exist in the National Marrow Donor Program registry, and the odds are much lower if the child is a member of an ethnic minority.

UCSF researchers are working on ways to improve the odds of getting a successful bone marrow transplant, even when there is no closely matched donor. Morton J. Cowan, M.D., has been director of the UCSF Pediatric Bone Marrow Transplant Program since 1981. He and his colleagues were among the first to use transplants from relatives who were not a perfect match, but "close enough" immunologically to treat kids with congenital immunodeficiencies. They are now trying to use their techniques for kids with cancer and other diseases of the bone marrow.

Bone marrow transplants between people who are not histocompatible result in an often fatal condition called graft-versus-host disease (GvHD), in which the donor's T cells attack the recipient's tissues. Close relatives of the patient who are not histocompatible, however, may be haplocompatible, or half-matched, sharing one out of two alleles of all genes in the HLA complex. Biological parents are always haplocompatible with their children, and siblings have a 50 percent chance of being haplocompatible with each other.

Cowan and his colleagues have found that transplanting peripheral blood stem cells from a haplocompatible donor can often result in a successful transplant if T cells are removed from the sample to eliminate the possibility of GvHD. Their approach involves a highly efficient technique that purifies the bone marrow stem cells, while at the same time eliminating the T cells. Cowan is still studying the effectiveness of using haplocompatible donors for children with genetic immunodeficiencies, but he is also now studying the use of the technique for children with leukemia, preleukemia, or certain marrow cell defects such as aplastic anemia or cytopenia.

Bone marrow stem cells circulate in the blood of normal individuals in small amounts, but that number can be increased by treating donors with a genetically engineered drug called granulocyte-colony stimulating factor (G-CSF). The stem cells can be harvested, along with other white blood cells, through leukapheresis. The bone marrow stem cells are then purified, using monoclonal antibodies that target the CD34 receptor, eliminating the T cells. Typically, the stem cells resulting from this operation are more than 95 percent pure, with less than 0.05 percent T cells left in the preparations. For the last decade, leukapheresis has routinely been used for autologous transplants, in which peripheral blood stem cells are collected from patients before radiotherapy or chemotherapy, so that the cells can be returned after treatment.

In addition to allowing patients the chance of a curative transplant, even without a matched donor, the benefits of Cowan's approach include a more rapid recovery of leukocytes following the transplant and a reduction in the number of transfusions needed. Unlike transplants using bone marrow or umbilical cord blood, in which the average hospital stay can be as long as 10 to 12 weeks, patients who receive haplocompatible bone marrow stem cell transplants are often discharged within six weeks. Another benefit is that the cell donation process is easier. Donors merely have to allow their blood to cycle through a machine, which can be done during a five-hour visit, rather than submitting to a bone marrow harvest that requires general anesthesia and multiple punctures of the hip bone. However, one of the big risks for these patients is infection during the time that it takes to develop their own stock of immune cells. Cowan and colleagues have focused on this issue and have developed novel approaches to accelerate immune recovery, which they are currently evaluating in selected patients.

Those interested in contacting Dr. Cowan or the Pediatric Bone Marrow Transplant Program can call (415) 476-2188. More information is available at

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