Increased risk of citrate reactions in patients with multiple myeloma during peripheral blood stem cell leukapheresis

Abstract

The citrate based anticoagulant ACD is commonly used in apheresis procedures. Due to its ability to decrease ionized calcium, citrate may cause unpleasant symptoms, such as paresthesias and muscle cramps, in patients undergoing therapeutic and donor apheresis. We noticed that patients with multiple myeloma (MM) undergoing autologous stem cell leukapheresis appeared to have more citrate reactions when compared to other patients undergoing the same procedure. A retrospective chart review was performed to evaluate 139 (of 151) consecutive patients with MM, amyloidosis, hematological and solid malignancies who had autologous peripheral blood stem cell collection between January 2007 and February 2008. Citrate reactions, ranging from mild (e.g., perioral tingling and parasthesias) to severe (e.g., nausea/vomiting and muscle cramps) were noted for 35 patients. Twenty-three of 63 patients with MM had documented citrate reactions, which was significantly higher than those with other hematological and solid malignancies (37% vs. 20%; P < 0.05, Relative Risk (RR) = 1.9). The severities of citrate reactions were the same in both groups; approximately 50% of patients in each group received i.v. calcium gluconate for treatment of hypocalcemia. No correlation between bisphosphonate therapy and citrate reactions were noted in our study group. Examination of available laboratory values related to calcium homeostasis, liver, and renal function failed to reveal a mechanism for the increase in citrate reactions observed. In summary, this single institution retrospective study indicates that patients with MM are more sensitive to citrate-induced hypocalcemia during leukapheresis when compared to patients with other hematological and solid malignancies. Strategies for decreasing citrate reactions (e.g., supplemental calcium and slowing return rates) should be considered for patient safety and comfort, especially in the MM population, on a prophylactic rather than reactive basis.

Does prophylactic calcium in apheresis cause more harm than good? – Centre heterogeneity within the World Apheresis Association Register prevents firm conclusions

“…In this study, the proportion of hypocalcaemia‐related AEs was similar to some , but not all retrospective reports . Noteworthy, the rate was minuscule compared to what was found in prospective intervention studies aiming to determine effect of calcium prophylaxis (with AE rates of 17% to 70%) .…”

Customizing anticoagulation strategies during leukapheresis to limit citrate exposure

“…A regimen to encompass both needs is therefore warranted. Reported strategies to reduce citrate‐related adverse events include a decrease in the overall setting of the AC infusion rate, slowing down the pumps or pausing the procedures for a while . We did not follow these approaches as these may cause significant delays in workflow.…”

“…This customization included elements such as lower platelet counts and the use of oral anticoagulants. Other aspects that are inherent to the patient's treatment schedule, such as diagnosis or co‐morbidities, were also taken into account.…”

A nomogram prediction of citrate reaction during mononuclear cell collection in solid tumor patients

“…Symptoms of hypocalcemia associated with high citrate concentrations often occur during therapeutic plasma exchange and MNC collection 5 . These symptoms range from mild (eg, numbness around the mouth and extremities, dizziness) to moderate (eg, nausea, muscle cramps) and severe (rarely, eg, tetany and arrhythmias) 6 . About 1.5% to 5% of patients experienced moderate to severe citrate‐induced hypocalcemia response during collection, requiring medical intervention 7 .…”

“…5 These symptoms range from mild (eg, numbness around the mouth and extremities, dizziness) to moderate (eg, nausea, muscle cramps) and severe (rarely, eg, tetany and arrhythmias). 6 About 1.5% to 5% of patients experienced moderate to severe citrate-induced hypocalcemia response during collection, requiring medical intervention. 7 Therefore, predicting the probability of hypocalcemia in solid tumor patients, in advance, can better prevent the occurrence of moderate and severe reactions, to ensure the smooth acquisition.…”