Fanconi Anemia

The Fanconi Anemia Comprehensive Care Program at the University of Minnesota Medical Center is the single largest treatment center for patients with Fanconi Anemia (FA) in the United States . The care provided is individually tailored to meet the unique needs of each patient and family. This program uses a team of expert health care providers who specialize in FA, applying leading-edge research developed by University of Minnesota scientists.  Due to our specialized research and care program, most patients come here for an initial consultation. Subsequent care is often managed by the home pediatrician/internist or hematologist with the guidance of the University of Minnesota team. When major treatments are required, Fanconi anemia patients usually return to the University of Minnesota for such care. Therefore, consultations early after diagnosis is optimal in order to individualize and coordinate treatment and follow-up.

For More Information

To receive more information about the Fanconi Anemia Comprehensive Care Program, contact the University of Minnesota Blood and Marrow Transplant Services at (612)273-2800 or (888)601-0787(toll-free).

What is Fanconi Anemia?

Fanconi Anemia is a rare, inherited disease which causes bone marrow failure. Those with FA have inherited one FA gene from their father and one from their mother. There are at least eleven different genes that cause FA. Approximately 1 in 80 (Ashkenazi Jews) to 600 (others) people carry the gene defect. Carriers are healthy and do not know that they carry the FA gene. If both parents are carriers, each child they have has a 25 percent chance of being affected by Fanconi Anemia. FA affects boys and girls equally.

Patients with Fanconi Anemia may have a number of unique medical problems. The University of Mnnesota has one of the most comprehensive programs for Fanconi in the world. More patients with Fanconi anemia are cared for here than all other facilities combined world-wide. Some of the treatments available through the Fanconi Anemia Comprehensive Care Program are:

1. Surgical correction of congenital anomalies
    a. Thumb and lower arm anomalies
    b. Heart, intestinal and/or kidney problems
2. Transplantation of bone marrow
3. Hormone replacement to correct
    a. Short stature
    b. Thyroid insufficiency
    c. Diabetes
4. Cancer treatment
5. Voice reconstruction (secondary to androgens)
6. Genetic counseling for
    a. Assisted reproduction and preimplantation genetic diagnosis
    b. Prenatal testing
    c. Family testing

At the University of Minnesota Medical Center, we have specialists in Fanconi Anemia to address each of your child's needs.

Diagnostic Tests/Genetic Counseling

After being diagnosed with Fanconi Anemia, extensive evaluations of the bone marrow are performed for clonal chromosomal abnormalities by experienced cytogeneticists.  Diagnostic tests may also be conducted before a child is born via an amniocentesis procedure or through chorionic villus sampling performed early in the pregnancy.  Genetic counseling is also available to help parents understand potential risks for Fanconi Anemia and various treatment options.

Bone Marrow Tests

Patients with Fanconi Anemia need to have a bone marrow test at least once a year to monitor for the development of myelodysplastic syndrome (MDS), leukemia or clonal cytogenetic abnormalities. If a cytogenetic abnormality is found, bone marrow examinations should be performed more frequently. Evaluations are performed by hematopathologists and cytogeneticists experienced specifically in FA.  There is special interest in determining marrow changes that predict leukemia.

Our Expertise

The University of Minnesota Medical Center, Fairview - Blood and Marrow Transplant (BMT) Services, affiliated with the University of Minnesota has set the standard for BMT as a treatment for Fanconi Anemia and other diseases since University of Minnesota Physicians performed the world's first successful BMT in 1968. University of Minnesota physicians have performed sibling donor transplants for FA since 1976 and unrelated donor transplants for FA since 1987.

In 2000, we broke ground by performing the world's first umbilical cord blood transplant on a Fanconi Anemia patient using preimplantation genetic testing to ensure a perfect HLA tissue match. As a result of this work, Fanconi Anemia patients have been referred at diagnosis or shortly thereafter to assist in the care of FA patients well in advance of BMT. Our patients are treated by a team of experts specializing in gastroenterology, nephrology, cardiology, orthopedic surgery, endocrinology, infectious diseases, nutrition, neurology, general surgery, otolaryngology and hand surgery.

Treatment for Fanconi Anemia

We follow FA patients carefully, well before the onset of bone marrow failure, myelodysplastic syndrome (MDS) and leukemia.  When bone marrow changes occur, patients may be initially managed with medications. However, at some point, the only treatment proven to cure the hematological abnormalities associated with FA is through hematopoietic cell transplantation (HCT) to replace the patient's abnormal stem cells with normal stem cells. Nonetheless, new treatments with and without hematopoietic cell transplantation are being explored.

Innovative, World Class Research

Areas include:

1. Gene correction of bone marrow stem cells. An outstanding team of investigators constantly strive to make gene therapy a viable option with out work done in collaboration with researchers at the Fred Hutchinson Cancer Research Center andOregon Health Sciences University
2. Isolation and expansion of the multipotent adult progenitor cell (MAPC) capable of differentiation into liver, lung, gastrointestinal tract, as well as blood and marrow. FA is slated to be the first indication for treatment with MAPC. This work is done in collaboration with Catherine Verfaillie, MD, Bruce Blazar, MD and Jakub Tolar , MD , PhD.  The first trial is to begin in late 2006.
3. Radioprotectants to reduce the side effects of radiation when employed in transplantation
4. New preparative regime to eliminate the use of radiation
5. Regulatory T cells to eliminate GVHD and enhance engraftment in the setting of reduced radiation therapy.

Hematopoietic Cell Transplantation

FA patients have unique challenges to transplantation including limits of a finding a match either through a sibling donor or unrelated stem cell donors, coupled with sensitivity to chemotherapy and radiation and a high incidence of congenital abnormalities.

The decision of when to transplant depends on various factors, including:

1. peripheral blood counts
2. presence of myelodysplastic syndrome or leukemia
3. presence of clonal cytogenetic abnormalities
4. type of stem cell donor available
5. overall health

Matched Sibling Donor HCT

Low-dose cyclophosphamide and limited field irradiation is the standard preparative therapy for patients with FA undergoing related-donor hematopoietic cell transplantation. However, long-term follow-up studies have demonstrated a high risk of malignancy, particularly of the head and neck. Reported potential risk factors include the use of radiation and chronic graft-versus-host disease (GVHD). In an attempt to reduce the risk of malignancy, at the University of Minnesota we have designed new protocols which replace radiation with fludarabine and ATG and reduce the risk of GVHD by T-cell depletion. As of 2002, all patients with a matched sibling donor using a radiation-free therapy have engrafted, and none have developed any acute or chronic GVHD.

Unrelated Donor Hematopoietic Cell Transplantation

Until recently, unrelated donor transplants for FA patients had poor outcomes. Drs. Wagner and MacMillan at the University of Minnesota have developed breakthrough protocols drastically improving survival rates. For the first time, the survival rate approaches that of matched sibling donor recipients. Recently, a chemotherapy-based protocol without radiation was developed for high-risk FA patients to avoid the potential long-term effects of irradiation.

Open Treatment Protocols for Fanconi anemia

 
New Directions at the University of Minnesota

University of Minnesota scientists continue researching ways to improve outcomes for FA patients.  Currently, they are leading the nation in several areas of research including:

• TBI dose de-escalation study to determine whether lower dose or elimination of TBI is possible in setting of unrelated donor BMT.
• Use of Preimplantation Genetic Diagnosis to create a healthy HLA-matched sibling donor
• Multipotent Adult Progenitor Cell (MAPC) Therapy to treat other tissues of the body rather than just the marrow
• Hematopoietic Stem Cell Gene Correction in Fanconi Anemia
• Immune reconstitution to reduce the risk of infection after BMT

Selected Journal Articles

MacMillan ML, Auerbach AD, Davies SM, DeFor TE, Gillio A, Giller R, Harris R, Cairo M, Dusenberry K, Hirsch B, Ramsay NKC, Weisdorf DJ and Wagner JE. Hematopoietic cell transplantation in patients with Fanconi Anemia using non-genotypically indentical donors: Results of a TBI dose escalation trial. British Journal of Haematology. 108:1-10, 2000.

Grewal SS, Kahn JP, Macmillan ML, Ramsay NKC and Wagner JE. Successful hematopoietic stem cell transplantation for Fanconi Anemia from an unaffected HLA genotypically-identical sibling selected using preimplantation genetic diagnosis. Blood. 103:1147-1151, 2004.

Wagner JE, Tolar J, Levran O, Scholl T, Deffenbaugh BS, Satagopan J, Ben-Porat L, Mah K, Dev Batish S, Kutler D, MacMillan ML, Hanenberg H and Auerbach AD: Germline mutations in BRCA2: Shared Genetic Susceptibility to Breast Cancer, Early Onset Leukemia and Fanconi Anemia. Blood. 103:3226-3229, 2004.

Tan PL, Wagner JE, Auerbach AD, DeFor TE, Slungaard A and MacMillan ML. Successful engraftment without radiation after fludarabine-based regimen in Fanconi Anemia patients undergoing genotypically identical donor hematopoietic cell transplantation. Pedatric Blood and Cancer. 46:630-636, 2006.

Wagner JE, Eapen M, MacMillan ML, Harris RE, Pasquini R, Boulad F, Zhang MJ and Auerbach AD. Unrealted donor bone marrow transplantation for the treatment of Fanconi Anemia. Blood. In press, 2007.