Temperature Safeguards and Peri‐Procedural Strategies for Stem Cell Collection in Cold Agglutinin Disease: A Case Report and Literature Review

ABSTRACT Cold agglutinins can result in red blood cell (RBC) agglutination and lysis at low temperatures. Temperature sensitivity during stem cell mobilization, processing, and infusion poses unique procedural challenges in patients with active cold agglutinins. A 49‐year‐old man presented at an outside hospital with severe hemolysis and was found to have an anti‐I cold agglutinin and a component of warm autoimmune hemolytic anemia, together with a positive COVID and Rhinovirus test. He was treated with RBC transfusions, steroids, and Rituximab. Bone marrow evaluation several months later at our institution demonstrated IgA‐kappa multiple myeloma and a rare, atypical B‐cell population of unclear significance. After induction therapy, autologous peripheral blood stem cell transplantation was recommended. The primary concerns were cold‐induced agglutination during apheresis collection of hematopoietic progenitor cells and during graft handling. This required coordination across hematology, apheresis, and cell therapy teams. The patient received cyclophosphamide for cytoreduction, granulocyte colony‐stimulating factor for mobilization, and sutimlimab for complement inhibition. The collection was performed using practical temperature mitigation strategies including environmental warming and insulation of extracorporeal components. The product was processed using prewarmed equipment, and cryopreservation was performed per institutional protocol. A total of 5.61 × 10 6 CD34 + cells/kg were collected without circuit alarms or visible agglutination. Conditioning with high‐dose melphalan and autologous infusion was completed without complication, with successful engraftment. This case highlights the feasibility of pragmatic, multidisciplinary temperature management strategies during stem cell collection and processing in patients with cold agglutinin disease.