Trial of Allogeneic Stem Cell Transplants From HLA Compatible, Related and Unrelated Donors After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine For Adult Patients With Lymphohematopoietic Disorders
Trial of Allogeneic Stem Cell Transplants From HLA Compatible, Related and Unrelated Donors After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine For Adult Patients With Lymphohematopoietic Disorders
This is a phase II, single-center study to evaluate the efficacy of a novel cytoreductive
 regimen followed by CD34+E- selected T cell depleted allogeneic stem cell (or soybean
 agglutinated and E-rosetted BM) transplant as treatment for patients with acute and chronic
 leukemias, lymphoma and myelodysplstic syndrome/PNH. The impact of the change in conditioning
 regimen and use of CD34-selected T cell depleted PBSCs on transplanted related morbidity and
 mortality and disease free survival will be assessed.
The purpose of this study is: (1) to try to kill any cancer or precancer cells that are in
 your body, and to reduce the side effects of a transplant, which we have seen in our previous
 studies, (2) to see if this treatment with a new recipe of radiation and chemotherapy can
 suppress your immune system enough for the stem cells to 'take' and grow, (3) to see if the
 specially prepared stem cells can grow in you without a problem called graft-versus-host
 disease (GvHD) occurring.

 One of the major side effects of any stem cell transplant is a condition known as graft vs.
 host disease or GVHD. GVHD is an immune reaction caused by certain cells from the
 transplanted stem cells called T-lymphocytes (or T-cells). The T-cells from your donor may
 see your organs as foreign and attack them. New ways to remove the T-cells from the stem
 cells before the transplant are being used to try and prevent GVHD. In some studies, the
 removal of T-cells from the stem cells has been successful for many patients in preventing
 both short-term (acute) and long-term (chronic) forms of GVHD. However, the removal of
 T-cells may increase the chance that the new bone marrow developing from the stem cells will
 be rejected or will not function well. Rejection of the transplant means that some of your
 own cells have survived the chemo and radiation therapy, and are attacking the new bone
 marrow cells. This condition can be lifethreatening because of an increased risk of
 infections and bleeding and would require your getting more treatment and additional stem
 cells. Studies like this one are designed to find better ways to avoid GVHD without
 increasing the risk of other problems such as graft rejection.
Inclusion Criteria:

 -  Histologically proven acute or chronic leukemia, non Hodgkins and lymphoblastic
 lymphoma or myelodysplastic syndrome

 -  HLA 6/6 or 5/6 antigen matched related or unrelated donor

 -  creatinine = normal or if not, CrCl > 60 ml/min/1.73ml

 -  total bilirubin < 2.5, AST < 2xnl, cardiac function > 50%

 -  pulmonary function - asymptomatic or if not DLCO > %50% (corrected for Hgb)

 -  Karnofsky performance status > 70%

 -  negative pregnancy test (where applicable)

 -  signed informed consent of patient and donor.

 Exclusion Criteria:

 -  Pregnancy or lactation

 -  unwillingness to comply with protocol treatment or follow-up

 -  uncontrolled infection

 -  HIV or HTLV positivity

 -  active CNS/skin disease