A Phase I Study Evaluating The Use Of Rft5-Dga To Deplete Alloreactive Cells For Patients With Fanconi Anemia After Haploidentical Stem Cell Transplantation

While stem cell transplantation has proven an effective means of treating a wide variety of diseases involving hematopoietic stem cells and their progeny, a shortage of donors has proved a major impediment to the widest application of the approach. Until recently, only MHC identical donors could be used with safety. Such donors were originally siblings or other closely related family members. Over the past decade, the growth of allogeneic donor panels has allowed transplantation with stem cells obtained from a volunteer donor panel.

While it is now possible to obtain HLA identical unrelated donor stem cells for approximately 75% of individuals of Northern European backgrounds, the situation for most other ethnic groups is much less satisfactory. Even when a matched donor can be found, the elapsed time between commencing the search and collecting the stem cells usually exceeds three months, a delay that may doom many of the neediest patients. Hence there has been considerable interest in making use of HLA haploidentical family donors. Most individuals have a first-degree relative who would be suitable for such protocols. Fanconi anemia (FA) is an autosomal recessive disorder characterized by the development of progressive aplastic anemia usually evident by about age seven years and often associated with various diverse congenital anomalies such as short stature, microcephaly, radial anomalies, horseshoe kidney, and cafe au lait spots.

This study will determine the number of donor lymphocytes that can be given to recipients of haploidentical stem cell transplants with Fanconi anemia after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin, and will result in a rate of Grade III/IV GVHD of < / = 25%.