Study of Mast Cell Precursors
Study of Mast Cell Precursors
This study will investigate mast cell precursors that circulate in the blood. In a group of
 diseases collectively known as mastocytosis, mast cells accumulate in abnormal amounts in the
 skin, lymphoid tissues, bone marrow, liver and spleen. Some forms of mastocytosis have a
 generally good prognosis; for others, the prognosis is poorer. There is no known cure for any
 form of the disease. A better understanding of mast cells and how they respond to certain
 substances may provide insights that will lead to effective treatments for mastocytosis.

 Patients with systemic mastocytosis and normal healthy volunteers between the ages of 20 and
 60 may be eligible for this 8-day study. Participants will undergo the following procedures:

 -  Day 1 Medical history, physical examination, and blood tests to assess general health
 status

 -  Days 2 through 6 Daily injections under the skin of G-CSF a hormone that stimulates
 white blood cell production

 -  Day 7 Leukapheresis a procedure for collecting large numbers of white blood cells. In
 leukapheresis, blood is drawn through a needle placed in an arm and channeled into a
 cell separator machine. The white cells are collected and the rest of the blood is
 returned to the body through a needle in the other arm. The procedure takes up to 3
 hours.

 -  Days 7 and 8 Blood draw (about 1 teaspoon) to monitor white blood cell counts.
The purpose of this protocol is to obtain large numbers of CD34+ cells from the peripheral
 blood of healthy volunteers and patients with systemic mastocytosis or other related
 allergic, hematological, and immunological conditions by leukapheresis for culture and
 characterization of mast cell progenitor cells and their response to various cytokines and
 anti-mitotic agents. Healthy volunteers and patients will be adults of both sexes from 18 to
 70 years of age. Granulocyte colony stimulating factor (G-CSF) will be administered to
 healthy volunteers at dose of 10 mcg/kg/day as a subcutaneous dose daily for 5 days not to
 exceed 960mcg. Patients will receive Plerixafor at a dose of 0.24 mg/kg as a single
 subcutaneous dose not to exceed 24mg the night before leukapheresis as a mobilizing agent for
 CD34+ cells. In identified patients where leukapheresis yield is considered adequate without
 stimulation by the principal investigator, leukapheresis may proceed without stimulation.
 Healthy volunteers will undergo a single leukapheresis at day 7, and patients will undergo a
 single leukapheresis at day 3 or 4. This is not a therapeutic protocol and does not involve
 reinfusion of any manipulated cells, viruses or DNA constructs back into human subjects.
-  SUBJECT INCLUSION CRITERIA:

 Healthy Volunteers must:

 1. Be 18-70 years of age

 2. Be healthy

 3. Have adequate peripheral venous access

 4. Have normal renal function (creatinine less than or equal to 1.5mg/dL; less than or
 equal to 1 plus proteinuria)

 5. Have normal hepatic function (bilirubin less than or equal to 1.5 mg/dL)

 6. Have normal hematologic function (WBC greater than or equal to 3000/mm(3);
 granulocytes greater than or equal to 1500/mm(3) ; platelets greater than or equal to
 175,000; hemoglobin greater than or equal to 12.5 g/dL)

 Patients must:

 1. Be 18-70 years of age

 2. Have mast cell hyperplasia compatible with a diagnosis of systemic mastocytosis
 (applicable to systemic mastocytosis patients only) or other allergic, hematologic, or
 immunologic condition

 3. Have adequate peripheral venous access or be willing to have a central line placed.

 4. First be admitted as inpatients under an existing NIH protocol

 5. Have preserved renal function (creatinine less than or equal to 2 mg/dL; less than or
 equal to 2 plus proteinuria)

 6. Have preserved hepatic function (bilirubin less than or equal to 1.5 mg/dL)

 7. Have preserved hematologic function (WBC greater than or equal to 3000/mm(3);
 granulocytes greater than or equal to 1500/mm(3) ; platelets greater than or equal to
 175,000; hemoglobin greater than or equal to 12.5 g/dL)

 All female subjects of childbearing potential:

 1. May be enrolled if using effective contraception

 2. Have a negative serum or urine pregnancy test determined within 72 hours before
 beginning Plerixafor or G-CSF administration

 SUBJECT EXCLUSION CRITERIA:

 All subjects must not meet any of the following criteria:

 Healthy Volunteers and patients must not:

 1. Have active bacterial, fungal or viral infections

 2. Have viral screens positive for HIV or hepatitis B or C

 3. Be pregnant or lactating

 4. Have a history of autoimmune disease such as rheumatoid arthritis, vasculitis,
 pyoderma gangrenosum or similar disorder

 5. Have any condition, which in the judgment of the investigator, might place the subject
 at undue risk

 Healthy Volunteers with any of the following will be excluded:

 1. Splenomegaly, pulmonary fibrosis and other related conditions

 2. Use of any investigative drugs within the past 12 months

 3. Have a significant coagulation disorder

 Systemic Mastocytosis and Mast Cell Related Condition Patients with any of the following
 will be excluded:

 1. Patients taking any other growth factors, cytokines or investigative drugs

 2. Patients who are hemodynamically unstable (blood pressure systolic of lower than 105
 or diastolic lower than 65)