A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies
Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or
nonmyeloablative conditioning, is a potentially curative treatment for a variety of
hematologic malignancies and non-malignant hematologic disorders. Of all the potential
sources of allografts, transplantation of stem cells from a human leukocyte antigen
(HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and
progression-free survival. Unfortunately, only about a third of candidates for alloBMT have
For patients who lack HLA-matched siblings, there are three alternative sources of stem
cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially
HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA
haplotype with each biological parent or child and half of siblings, an eligible
haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical
BMT has been associated with significant risks of graft rejection and severe GVHD, which are
manifestations of excessive alloreactivity by host and donor T cells, respectively.
The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that
have been rigorously depleted of mature T cells or selectively depleted of alloreactive T
cells, but the risks of serious infection and death from prolonged immune compromise in
these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive
antineoplastic agent that has an established role in conditioning for alloBMT.
Typically, the drug is administered prior to transplantation to prevent graft rejection by
suppressing the host immune system. However, pre-transplantation conditioning with Cy
increases the risk of GVHD following allogeneic T cell infusion in mouse models. In
contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft
rejection and GVHD.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening
To estimate the incidence of donor cell engraftment following myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies.
Heather Symons, M.D.
Johns Hopkins University
United States: Institutional Review Board
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231|
|Sidney Kimmel Comprehensive Cancer Center||Lutherville, Maryland|