Mobilization and Handling of Stem Cells for Transplant From Healthy Volunteers With Sickle Cell Trait

Overview

This study will examine the effects of granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells in healthy volunteers with sickle cell trait and determine if cells collected for transplantation from donors with sickle cell trait require special handling. Stem cells, which the bone marrow produces, are responsible for making all the different kinds of blood cells. They are the cells used in bone marrow, or stem cell, transplantation. The drug G-CSF, which is a naturally occurring hormone, causes stem cells to mobilize-that is, to be released from the bone marrow and enter the blood stream. This drug is given to stem cell donors to increase the amount of cells that can be collected. Stem cell donors for patients with sickle cell disease are often healthy siblings of the patient who have a matching bone marrow type. Some siblings carry the sickle cell trait, however, and, even though they do not have sickle cell disease and their blood and bone marrow are normal, it is not known how their cells will react to G-CSF stimulation. Nor is it known if their stem cells require special methods of removal, processing or storing. Healthy volunteers 18 years or older with sickle cell trait who have no history of sickle cell disease and no known medical problems may be eligible for this study. Participants will have a medical history and physical examination, including blood tests and urinalysis. They will receive injections of G-CSF under the skin once a day for 5 days. On the fifth day, stem cells will be collected through leukapheresis. In this procedure, whole blood is drawn from an arm vein, similar to donating whole blood. The blood then circulates through a cell separator machine, the stem cells are removed, and the rest of the blood is transfused back to the donor through a vein in the other arm. The information gained from this study will be used to ensure the safety of stem cell donors with sickle cell trait and to better prepare stem cells for transplantation in sickle cell patients.

Patients with sickle cell disease are increasingly becoming eligible for transplantation as the techniques of stem cell transplantation continue to improve, leading to less morbidity and mortality. However, the availability of a matched donor still remains one of the main obstacles. Given the inherited nature of this disease, many HLA-matched siblings of patients with sickle cell disease have sickle cell trait. Therefore, patients with sickle cell trait presumably have been used as donors for patients with sickle cell disease. However, there are no published data on whether special manipulations are required for the maintenance and storage of stem cells collected from patients with sickle cell trait. The effects of granulocyte-colony stimulating factor (G-CSF)-induced stem cell mobilization in these patients are also not known. Also, due to the potential of HbS gellation in red cells, the freezing of stem cells derived from individuals with sickle cell trait may require a more stringent red cell removal than is normally performed. We would like to evaluate these issues using volunteers with sickle cell trait prior to beginning our own transplant protocol for sickle cell disease.