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 patients with systemic mastocytosis or other related immunological conditions, and normal volunteers by leukapheresis for culture and characterization of mast cell progenitor cells and their response to various cytokines and anti-mitotic agents. Granulocyte colony stimulating factor (G-CSF) will be administered to normal volunteers at doses of 10 microg/kg/day as a single subcutaneous dose daily for 5 days. Normal volunteers and mastocytosis patients will be adults of both sexes from 18 to 60 years of age. Normal volunteers and patients will undergo a single leukapheresis at day 7. A small number of normal volunteers and all mastocytosis patients will undergo leukapheresis without G-CSF mobilization. This is not a therapeutic protocol and does not involve reinfusion of any manipulated cells, viruses or DNA constructs back into human subjects.

• Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y, Metcalfe DD. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10560-4.
• Kirshenbaum AS, Kessler SW, Goff JP, Metcalfe DD. Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells. J Immunol. 1991 Mar 1;146(5):1410-5.
• Rottem M, Okada T, Goff JP, Metcalfe DD. Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population. Blood. 1994 Oct 15;84(8):2489-96.

• INCLUSION CRITERIA:

Normal Volunteers - ages 18-60:

Healthy without active infection or history of recurrent infections.

Normal renal function (creatinine less than or equal to 1.5 mg/dl; less than or equal to 1+ proteinuria); normal hepatic function (bilirubin less than or equal to 1.5 mg/dl); 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).

Normal female volunteers of childbearing potential may be entered if using contraception, and with a negative urine pregnancy test determined the day before beginning G-CSF administration.

Patients - ages 18-60:

Systemic mastocytosis patients must have mast cell hyperplasia compatible with a diagnosis of systemic mastocytosis; and be without active infection or history of recurrent infections.

Preserved renal function (creatinine less than or equal to 2mg/dl; less than or equal to 2+ proteinuria); preserved hepatic function (bilirubin less than or equal to 1.5 mg/dl); 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).

Normal female volunteers of childbearing potential may be entered if using effective contraception, and with a negative urine pregnancy test determined the day before beginning G-CSF administration.

EXCLUSION CRITERIA:

NORMAL VOLUNTEERS:

Active bacterial, fungal or viral infections.

HIV+, HCV+.

Pregnancy or lactation.

History of autoimmune disease such as rheumatoid arthritis, vasculitis, pyoderma gangrenosum or similar disorder.

Use of any investigative drugs.

Any condition which in the judgment of the PI might significantly increase the risks of mobilization or aphereses.

SYSTEMIC MASTOCYTOSIS PATIENTS:

Active bacterial, fungal or viral infections.

HIV+, HCV+.

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

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

Pregnancy or lactation.

History of autoimmune disease such as rheumatoid arthritis, vasculitis, pyoderma gangrenosum or similar disorder.

Any condition which in the judgment of the PI might significantly increase the risks of mobilization or aphereses.