Low Intensity Preparative Regimen Followed by HLA-Matched, Mobilized Peripheral Blood Stem Cell Transplantation for Systemic Mastocytosis
Mastocytosis is a disease characterized by excessive numbers of mast cells in skin, bone
marrow and internal organs such as liver, spleen and lymph nodes. Its genesis appears to be
related to somatic mutations in c-kit, the receptor for mast cell growth factor. Although
most patients present with the indolent form of the disease, approximately one-third of the
patients have an associated hematologic disorder such as a myeloproliferative state or
myelodysplastic syndrome. Patients with advanced forms of the disease, including those with
an associated hematologic disorder have a poorer prognosis than those with indolent disease.
There is no treatment known to cure or improve the natural course of mastocytosis. Since
mast cells arise in the bone marrow from a CD34+ progenitor, bone marrow transplantation may
offer the only hope for a cure.
In this protocol, we propose to treat patients with advanced forms of mastocytosis with an
allogeneic stem cell transplant from an HLA-identical sibling, using a low intensity
non-myeloablative regimen. This approach has the advantage of decreasing the
transplant-related toxicity while allowing adequate immunosuppression to establish stem cell
and lymphocyte engraftment. Donor derived CD4 and CD8 lymphocytes, which are important in
killing of leukemic cells by mounting a "graft versus leukemia" effect, should be useful in
the elimination of aberrant mast cells and their progenitors, that is "graft-versus-mast
cell effect". This mechanism may be particularly relevant in mastocytosis as point
mutations of c-kit may constitute an antigenically distinct T-cell target for recognition by
the engrafted donor cells.
The primary end point of this study is regression of mastocytosis. The secondary end points
are engraftment, hematologic response, degree of donor-host chimerism, incidence and
severity of acute and chronic GVHD, transplant related morbidity and mortality, relapse,
disease free survival, and overall survival.
Primary Purpose: Treatment
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|