Large volume leukapheresis (LVL) is increasingly used to collect peripheral blood stem cells (PBSCs) and other mononuclear cells (MNC) for hematopoietic and immune reconstitution, with recent emphasis on increased processing volumes. Decreases in divalent cation levels caused by administration of citrate anticoagulant during LVL can be associated with severe donor reactions, and may limit the rate at which blood can be processed. Several donors at NIH experienced citrate-related hypocalcemic tetany during LVL, in response to which we developed standard operating procedures for the routine administration of prophylactic intravenous calcium solutions during longer apheresis procedures. Other centers have utilized heparin to reduce the amount of citrate returned to the donor, however, this exposes the donor to systemic anticoagulation and may be associated with hematomas or clumping of the apheresis product.

We previously determined that citrate administration during apheresis results in significant excretion of calcium and magnesium in the urine during the procedure, and that performance of prolonged or repeated LVL causes significant depletion of blood calcium and magnesium levels. Decreases in calcium levels were ameliorated during procedures performed with prophylactic calcium administration. Our preliminary studies also demonstrated that ionized magnesium levels were markedly reduced during LVL as well as plateletpheresis procedures. The clinical impact of severe, acute decreases in ionized magnesium levels in healthy apheresis donors is not clear, however. Since most of the adverse effects related to citrate administration can be prevented by prophylactic calcium administration, it is unknown what aspect of the remaining discomfort may be attributable to hypomagnesemia. This protocol will focus on determining the contribution of acute hypomagnesemia to citrate-related symptoms during large-volume apheresis, and establishing the role of and indications for prophylactic intravenous magnesium replacement in this setting. The study plan will consist of a prospective, randomized, placebo-controlled, double-blind study. Healthy allogeneic donors will be assigned to one of two treatment groups. One group will receive intravenous magnesium infusions throughout scheduled LVL procedures; the other group will receive equivalent volume infusions of normal saline. Symptoms and blood samples will be obtained by apheresis nurses and laboratory assays will be performed by associate laboratory investigators, all in a blinded fashion.