Haplocompatible Donor Program

With only rare exceptions, a parent will be haplocompatible, or half-matched, with his or her child and a sibling has a 50% chance of being haplocompatible. The purpose of the Haplocompatible Donor Program is to study the effectiveness of using stem-cell enriched, T-cell depleted peripheral blood stem cells (PBSC) for transplantation into children with leukemia, pre-leukemia or certain marrow cell defects such as aplastic anemia, cytopenias, or severe immunodeficiency diseases. The program evaluates the ability of this processed source of marrow stem cells, along with high dose chemotherapy and radiation therapy (except for SCID), to engraft and restore the functioning of the body's immune system.

T cell depletion

In order for a haplocompatible donor bone marrow transplant to work, the stem cells must be specially treated after they are collected from the donor and before they are transplanted into the patient. This treatment depletes them of the donor T lymphocytes, white cells that are important for fighting infection and cancer cells in the body. Donor T cells can also cause a reaction called graft vs. host disease (GVHD) when they attack certain tissues or organs (e.g., the eyes, skin, liver, intestines, lungs) of the transplant recipient.

The risk of GVHD increases the more mismatched or incompatible the donor is with the recipient. Parents and most siblings are usually only partially compatible with their children and can only donate marrow or PBSC if it is treated to remove the T cells that are responsible for GVHD.

There are advantages and disadvantages to T cell depletion. The technique that we use significantly reduces the risk of GVHD both in terms of its chances of occurring, as well as its severity if it does occur. However, there is an added risk that the marrow might not engraft. In order to improve the chances that it will engraft (>95%), radiation treatment must be added to the conditioning regimen in most cases. Also, there may be a delay in the recovery of the immune system (the body's defense against infection) resulting in a higher risk of infections after transplant. T cell depleted marrow from a parent may be considered for children who do not have an HLA matched related or unrelated donor. Recently, we have developed a novel protocol that focuses on optimizing engraftment while minimizing the delay in immune reconstitution.

Peripheral blood stem cells (PBSC) for haplocompatible transplantation

Bone marrow stem cells can be collected from the blood that circulates throughout the body in arteries and veins. It is known that when normal people are treated with a type of chemical normally made in small amounts in the body called G-CSF (granulocyte colony stimulating factor), increased numbers of stem cells leave the marrow and enter the blood stream. These cells, referred to as peripheral blood stem cells, or PBSC, can be collected along with other white cells by a process called leukapheresis, a standard procedure commonly used in blood banks. In the past 10 years, leukapheresis has been used routinely for collecting stem cells from patients with cancer for subsequent transplantation back into the patient. Recently, it has been used for collecting stem cells from healthy parents or siblings for transplantation into matched or mismatched children or adult patients.

The UCSF Pediatric BMT Program is researching answers to the following questions regarding PBSC transplants:

• How often will the transplants engraft?
• How safe is the procedure?
• Will there be a sufficient number of healthy donor stem cells to restore marrow function?
• Will secondary or "booster" transplants be necessary after the initial transplant to accelerate the recovery of the immune system?
• Are there any complications associated with this particular source of bone marrow stem cell?

Eligibility for the Haplocompatible Donor Program

Children who might be eligible for the Haplocompatible Donor Program include those with the following diagnoses:

• Acute lymphoblastic leukemia (ALL) in second or third morphologic remission ;
• Myelodysplasia prior to transition to frank leukemia;
• Chronic myelogenous leukemia (CML) in first or second chronic phase;
• Juvenile myelomonocytic leukemia (JMML);
• Acute myelogenous leukemia (AML) in 2nd or 3rd remission;
• Severe aplastic anemia (ANC<500, platelet &/or red cell transfusion dependent, not Fanconi’s anemia) unresponsive to immunosuppressive therapy;
• Congenital marrow aplasias unresponsive to cytokines and transfusion dependent;
• Inherited immunodeficiency diseases including Chediak-Higashi Disease, Wiskott-Aldrich Syndrome, Combined Immunodeficiency Disease (Nezelof’s), Hyper IgM Syndrome (CD40 ligand deficiency).
• Children with severe combine immunodeficiency disease (SCID) are eligible for a separate protocol using haplocompatible donors and a low intensity conditioning regimen.

In addition, the patient must not have a closely matched related or unrelated donor available in sufficient time to do the transplant. A haplocompatible relative including parent or sibling who is at least 12 years of age must be available and willing to donate.

Patients who are in relapse, who have active infections, significant heart, kidney, lung or liver abnormalities or who are less than 6 months of age will not be eligible for this research program.