Non-Myeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Chronic Phase CML
CML is a disease which progresses to blast crisis within five years of onset despite medical
intervention. Allogeneic transplantation has provided a definitive cure for a large number
of patients. The International Bone Marrow transplant registry reports a 67% three-year
disease free survival for CML patients receiving a matched sibling transplant. However
there remains a 17-20% treatment-related mortality and significant long-term complications.
Myeloablative regimens with total body irradiation (TBI) are associated with certain
sterility, along with a significant incidence of cataracts and second malignancies. Efforts
to ameliorate this toxicity have led to the development of regimens lacking total body
irradiation. Although the follow-up period for patients receiving these regimens has not
been long enough to answer the question of long-term toxicity, it appears that the response
rate and the disease free survival are comparable to regimens containing TBI. In addition,
transplantation experience with aplastic anemia where TBI is not part of the regimen
indicates that treatment related mortality along with the risk of long-term sequela are
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being
investigated in phase I/II trials assessing engraftment efficacy and toxicity at a number of
transplant centers. Preliminary data, including our own experience with 30 patients
undergoing this type of procedure, has shown a high rate of complete donor engraftment with
a low toxicity profile. Two recent studies investigating non-myeloablative
allo-transplantation in standard risk patients revealed an extremely low rate of
transplant-related complications and mortality.
In this protocol we investigate non-myeloablative allogeneic PBSC transplantation in
patients with CML. The patient group under study would include all patients with chronic
phase CML having an HLA-identical sibling. In this protocol, eligible patients would be
treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or
single HLA antigen-mismatched family donor, using an intensive immunosuppressive regimen
without myeloablation ("mini-transplant") in an attempt to decrease the transplant related
toxicities while preserving the anti-malignancy and/or anti-host marrow effect of the graft.
The low intensity non-myeloablative conditioning regimen should provide adequate
immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete,
donor-derived, granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem
cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution. We will
add back lymphocytes in patients with less than 100% donor T-cell chimerism in an attempt to
prevent graft rejection and enhance a graft-versus-malignancy effect.
The primary endpoint of this study is transplant related mortality (1 year survival). Other
end points include engraftment, degree of donor-host chimerism, incidence of acute and
chronic graft versus host disease (GVHD), transplant related morbidity, as well as
disease-free and overall survival.
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
United States: Federal Government
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