Stem Cell Transplantation to Treat Systemic Mastocytosis
Condition: Mastocytosis
MeSH terms: Mastocytosis; Mastocytosis, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will investigate the safety and effectiveness of an experimental stem cell
      transplant procedure for treating mastocytosis-a disease of abnormal mast cell growth.
      Patients often feel faint, have skin problems, joint and bone pain, low blood counts and
      enlarged liver, spleen or lymph nodes. As yet, there is no cure for mastocytosis, and
      treatment is aimed at controlling symptoms.

      Stem cells are cells produced by the bone marrow that mature into the different blood
      components-white cells, red cells and platelets. Transplantation of allogeneic (donated) stem
      cells is a mainstay of therapy for some forms of leukemia. Patients first receive intensive
      chemotherapy and radiation to rid the body of cancer cells. This "conditioning" is followed
      by transplantation of donated stem cells to generate new, healthy bone marrow. In addition to
      producing the new bone marrow, the donated cells also fight any residual tumor cells that
      might have remained in the body. This is called a "graft-versus-tumor" effect. This study
      will examine whether a stem cell transplant from a healthy donor can similarly target and
      destroy mast cells in a "graft-versus-mast cell" effect. Also, to try to reduce the harmful
      side effects of chemotherapy and radiation, this study will use lower dose chemotherapy and
      no radiation.

      Patients with advanced mastocytosis between 10 and 80 years old may be eligible for this
      study. They will be

      tested for HLA type matching with a sibling and will undergo a medical history, physical
      examination and several tests to determine eligibility for the study.

      Participants will undergo apheresis to collect lymphocytes (a type of white blood cell) for
      immune function tests. In this procedure, blood is drawn through a needle in the arm, similar
      to donating a unit of blood. The lymphocytes are then separated and collected by a cell
      separator machine, and the rest of the blood is returned through a needle in the other arm.
      Patients will also have a central venous line (flexible plastic tube) placed in their upper
      chest leading to a vein. This line will remain in place throughout the transplant and
      recovery period and will be used to transfuse blood components, administer medicines, infuse
      the donated stem cells, and draw blood for tests. Patients will begin conditioning with
      cyclophosphamide, starting 7 days before the transplant, and fludarabine, starting 5 days
      before the transplant, to prevent rejection of the donated cells. From 1 to 3 days after the
      chemotherapy is completed, the stem cells will be transfused through the central venous line.
      Also, from 4 days before the transplantation until about 3 months after the procedure,
      patients will receive cyclosporine and mycophenolate mofetil-drugs that help prevent both
      rejection of the donated cells and attack by the donor cells on the patient's cells (called
      graft-versus-host disease).

      Patients will stay in the hospital about 20 to 30 days after the transplant. After discharge,
      they will continue to take antibiotics, cyclosporine and mycophenolate mofetil at home. If
      the mastocytosis progresses, cyclosporine and mycophenolate mofetil will be tapered over 4
      weeks. If the mastocytosis persists, patients may receive additional transfusions of donor
      lymphocytes to help kill the mast cells.

      Patients' progress will be followed weekly or twice weekly for 3 months, then at 6, 12, 18,
      24, 30, 36, 48 and 60 months after transplant, and then twice a year for various tests,
      treatments and examinations.
    

Detailed description: 
      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.
    

Intervention name(s): Stem cell transplantation
Intervention type(s): Procedure
Primary purpose: Treatment
Keywords: Peripheral Blood Stem Cells; Non-Myeloablative Bone Marrow Transplantation; Engraftment; Graft-versus-host Disease; Graft-Versus-Leukemia; Graft-Versus-Mast Cell; Cyclophosphamide; Fludarabine; Donor Apheresis; Mast Cells