Trial Information

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using Two Related Donors

At Jefferson, a 2 step process of performing bone marrow transplants (HSCT) was developed in
2005. In this process, subjects are given their donor cells at 2 different times. First,
after receiving radiation and/or chemotherapy to help their immune system accept donor cells
and further fight their disease, subjects receive a specific amount of donor T cells. (Step
1 of the HSCT). The donor T cells fight the cancer and help the subject fight infection and
accept a new immune system. Donor T cells can also irritate the tissues of the subject's
body, especially their skin, gut, and liver. This condition can be life threatening and is
called graft versus host disease or GVHD. To decrease the incidence and severity of GVHD,
after the subjects receive their donor's T cells, they are given a drug called
cyclophosphamide (CY). This drug eliminates the most active donor T cells, but leaves behind
some T cells to help fight infection. Step 2 of the HSCT occurs when the subject receives
their donor's stem cells to help their blood counts recover.

There have been low rates of serious GVHD and toxicity using the 2 step approach. Over 100
transplants (using 1 donor) have been performed at TJUH using this method. Patients who go
to transplant while their disease is under control have had good outcomes. However, subjects
whose disease is active at the time of the HSCT (especially subjects with acute leukemia)
have had a high incidence of relapsing after HSCT. Relapse after HSCT usually results in
death. There have not been any significant advances in the field regarding improving
outcomes for subjects with disease at HSCT.

The rationale for the current study is as follows. Transplants using donor cells work not
just because the subject receives chemotherapy and radiation therapy, but because the donor
cells themselves can recognize the cancer when it tries to come back and eradicate it. This
is called a graft versus tumor effect or GVT. Therefore the recognition of the tumor by the
donor cells is key to the prevention of relapse and long term survival. When a subject
relapses after HSCT, it is because the cancer cells were able to avoid recognition by the
new donor immune system. In this research study, the investigators will use two donors
instead of one. Our hypothesis is that the cells from two donors will have a better chance
at recognizing and eradicating the malignancy than cells from one donor.