A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
Patients with this disease are born with it and have a fragility of the genes (chromosomes)
in all the cells of the body. The fragility of the chromosomes puts patients with FA at high
risk for certain cancers. Patients with FA are especially at risk of having diseases of the
blood and marrow systems. These include (1) aplastic anemia, a disease where there is a
failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is
represented by a clone of cells of the marrow that becomes "malignant" and stops making
adequate numbers of blood cells (it is also called preleukemia.) The progression of the
myelodysplastic syndrome will lead to (3) acute leukemia.
If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or
leukemia standard treatment with medications or chemotherapy alone is not likely to cure
these problems.
An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to
provide you with marrow or blood stem cells from a healthy donor that can develop a normal
blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow
and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic
stem cell transplants have been done for the treatment of FA using stem cells from donors
other than matched siblings, they have been associated with a high risk of rejection of the
transplant and of a complication called graft-versus-host disease.
In order for the stem cells to grow and to kill leukemia cells, patients must receive
chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients
with Fanconi anemia, the standard preparation for stem cell transplantation has been the use
of total body irradiation (at a lower dose because of the high risk of side-effects) and a
chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has
worked well with transplants from matched siblings, it was not enough in transplants from
unrelated or cord blood donors and led to a high risk of rejection. In the last few years a
medication called fludarabine was used successfully in transplants to give more
immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low
risks of rejection, and probably as importantly little risks of added side-effects. The
addition of antithymocyte globulin to TBI, cyclophosphamide and fludarabine has made the
chances of rejection very low.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence & quality of engraftment & hematopoietic reconstitution/Early transplant-related severe morbidity & mortality/Incidence & severity of acute & chronic GvHD/Quality of immune reconstitution following transplantation/Overall survival rate.
8 years
Yes
Farid Boulad, MD
Principal Investigator
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
01-062
NCT00595127
June 2001
May 2013
Name | Location |
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Memorial Sloan Kettering Cancer Center | New York, New York 10021 |