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Low Intensity Preparative Regimen Followed by HLA-Matched, Mobilized Peripheral Blood Stem Cell Transplantation for Systemic Mastocytosis

Phase 2
2 Years
80 Years
Not Enrolling

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Trial Information

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.

Inclusion Criteria


Ages greater than or equal to 2 to 80.

Wt greater than 40 kg.

Patients with systemic mastocytosis proven by a bone marrow biopsy and one of the

Category I disease with poor prognosis secondary to extensive bone marrow involvement of
mast cells (i.e. greater than 50 percent of the bone marrow cavity replaced by mast cells)
and evidence of a bone marrow failure state defined as presence of one of the following
for greater than or equal to 2 months:

- Neutrophil count less than 500/ mm3.

- Platelet count less than 20,000/mm3.

- Dependency on transfusion of RBC or platelets.

Category II disease with an associated hematologic disorder:

- Myelodysplastic syndromes.

- Myeloproliferative states except essential thrombocytosis or polycythemia vera.

- Increased blasts in peripheral blood or bone marrow greater than 10 percent.

- Bone marrow failure states as described above.

Category III disease with enlarged peripheral lymph nodes with histopathological evidence
of the replacement of the entire lymph node architecture with mast cells and/or
accompanying peripheral eosinophilia. We also consider aggressive systemic mastocytosis
with local tissue invasion as category III disease.

Category IV disease with mast cell leukemia, characterized by the presence of malignant
mast cells in the peripheral blood, which constitute greater than 10 percent of the
nucleated cells.

No major organ dysfunction precluding transplantation.

DLCO greater than or equal to 65 percent predicted.

Left ventricular ejection fraction of greater than or equal to 40%.

ECOG performance status of 0 or 1.

Life expectancy of more than 3 months.

HLA-identical sibling available as donor.

Patients or their parent(s)/responsible guardian(s) must be able to comprehend the
investigational nature of the study and be willing to sign an informed consent.


HLA identical family donor, (only HLA identical).

Weight greater than or equal to 18 kg.

Age less than or equal to 80 years old.

Informed consent given.

EXCLUSION CRITERIA: PATIENT (Any of the following)

Pregnant or lactating

Age less than 2 or age greater than 80 years.

Weight less than or equal to 40 kg.

ECOG performance status of 2 or more.

Psychiatric disorder or mental deficiency severe as to make compliance with the BMT
treatment unlikely, and making informed consent impossible.

Major anticipated illness or organ failure incompatible with survival from PBSC

DLCO less than 65 percent predicted.

Left ventricular ejection fraction less than 40%.

Baseline GFR less than 50ml/min: measured or calculated by the following formula: GFR =
{(140-age) x body weight in kg}/72 x serum creatinine (for females, multiply by 0.85).

Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit
of normal.

Other malignant diseases liable to relapse or progress within 5 years.

Life expectancy of less than 3 months.

EXCLUSION CRITERIA: DONOR (Any of the following)

Pregnant or lactating.

Donor unfit to receive G-CSF and undergo apheresis (Uncontrolled hypertension, history of
congestive heart failure or unstable angina, thrombocytopenia).

HIV positive. Donors who are positive for HBV, HCV or HTLV-1 may be used if the
risk-benefit ratio is considered acceptable by the patient and investigator.

Weight greater than 18 kg.

Age greater than 2 or less than 80 years.

Type of Study:


Study Design:

Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

October 2000

Completion Date:

December 2006

Related Keywords:

  • Mastocytosis
  • 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
  • Mastocytosis
  • Urticaria Pigmentosa
  • Mastocytoma
  • Mastocytosis, Systemic



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892