Large volume leukapheresis (LVL) is defined as processing greater than three blood volumes, or greater than 15 liters of whole blood in an adult, during a single leukapheresis (white blood cell collection) procedure. LVL is increasingly being used to harvest peripheral blood stem cells (PBSC) and other mononuclear cells (MNC) for hematopoietic transplantation and immune reconstitution. 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 used heparin to reduce the amount of citrate given to the donor during the procedure, 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 was associated with a marked increase in urinary excretion of calcium and magnesium during the procedure, and that performance of prolonged or repeated LVL caused rapid and significant decreases in blood calcium and magnesium levels. Decreases in calcium levels were ameliorated during procedures performed with prophylactic administration of intravenous calcium solutions. Our preliminary studies also demonstrated that ionized magnesium levels were markedly declined during LVL. The clinical impact of severe, acute decreases in ionized magnesium levels in healthy apheresis donors was 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 PBSC or MNC donors will be assigned to one of two treatment groups. One group will receive intravenous magnesium infusions throughout all scheduled LVL procedures; the other group will receive an infusion of an equivalent volume of intravenous normal saline as placebo. Symptom scores and blood samples will be obtained by apheresis nurses at periodic sampling intervals. Laboratory assays will be performed by associate laboratory investigators in a blinded fashion. To date, five subjects have accrued to the study and undergone a total of nine LVL procedures using intravenous magnesium or saline infusions. The treatment assignment code has not been broken, and thus the symptom scores and laboratory data have not yet been evaluated. Fifty-two subjects will be studied, 26 in each group (magnesium replacement versus saline placebo).
