Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies
Status:
Completed
Trial end date:
2009-02-01
Target enrollment:
Participant gender:
Summary
Relapsed disease is the most common cause of death in children with hematological
malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or
relapse after stem cell transplantation have a poor prognosis. Toxicity from multiple
therapies and elevated leukemic/tumor burden usually make these patients ineligible for the
aggressive chemotherapy regimens required for conventional stem cell transplantation.
Alternative options are needed. One type of treatment being explored is called haploidentical
transplant.
Conventional blood or bone marrow stem cell transplant involves destroying the patient's
diseased marrow with radiation or chemotherapy. Healthy marrow from a donor is then infused
into the patient where it migrates to the bone marrow space to begin generating new blood
cells. The best type of donor is a sibling or unrelated donor with an identical immune system
(HLA "match"). However, most patients do not have a matched sibling available and/or are
unable to identify an acceptable unrelated donor through the registries in a timely manner.
In addition, the aggressive treatment required to prepare the body for these types of
transplants can be too toxic for these highly pretreated patients. Therefore doctors are
investigating haploidentical transplant using stem cells from HLA partially matched family
member donors.
Although haploidentical transplant has proven curative in many patients, this procedure has
been hindered by significant complications, primarily regimen-related toxicity including
graft versus host disease (GVHD), and infection due to delayed immune reconstitution. These
can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens
when the donor T cells recognize the patient's (the host) body tissues are different and
attack these cells. Although too many T cells increase the possibility of GVHD, too few may
cause the recipient's immune system to reconstitute slowly or the graft to fail to grow,
leaving the patient at high-risk for infection. However, the presence of T cells in the graft
may offer a positive effect called graft versus malignancy or GVM. With GVM, the donor T
cells recognize the patient's malignant cells as diseased and, in turn, attack these diseased
cells.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T
cell depleted product to reduce the risk of GVHD, yet provide a sufficient number of cells to
facilitate immune reconstitution, graft integrity and GVM.
In this study, patients were given a haploidentical graft engineered to with specific T cell
parameter values using the CliniMACS system. A reduced intensity, preparative regimen was
used to reduce regimen-related toxicity and mortality. The primary goal of this study is to
evaluate overall survival in those who receive this study treatment.