Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults
Patients with adult leukemias, non-Hodgkin's lymphoma and multiple myeloma, can now be cured
by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to
the use of high dose chemoradiotherapy and the antileukemia effect of the graft.
The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and
total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation
in adults to those under the age of 55 years. Toxicity related mortality increases
progressively with age and although some transplant centers carry out BMT in patients up to
the age of 60 years, it is generally accepted that treatment related mortality prohibits the
use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8
positive lymphocytes with specific reactivity for the patients' leukemia and a potent graft
versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML
after bone marrow transplantation where a single infusion of donor lymphocytes can induce
In this protocol, we treat older patients between the ages of 55 to 71 years with
hematologic disorders with an allogeneic stem cell transplant from an HLA identical sibling,
using intensive immunosuppressive regimen without myeloablation in attempts to decrease the
transplant related toxicity while preserving the antileukemia effect of the graft. The low
intensity nonmyeloablative conditioning regimen will 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 immune reconstitution. We will add back lymphocytes
in patients with less than 75% donor marrow chimerism as an attempt to prevent graft
The end points of this study are engraftment, degree of donor-host chimerism, incidence of
acute and chronic GVHD, transplant related morbidity and mortality as well as survival.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant.
A. John Barrett, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|