A Cold Case: Cold Agglutinin Disease Complicating Stem Cell Transplant

Allogeneic hematopoietic cell transplants (HCTs) offer a curative option for patients with life-threatening hematologic diseases. While stem cell infusion reactions are common, they are generally not severe and typically do not affect engraftment. We present a rare case of isolated secondary cold agglutinin syndrome (CAS) in a donor, complicating the graft infusion and causing poor graft function (PGF) in a recipient. The 27-year-old recipient, diagnosed with refractory T-cell acute lymphoblastic leukemia (ALL), underwent a 9/10 HLA-mismatched unrelated peripheral blood stem cell transplant. The donor developed an upper respiratory infection 1 week before the donation, and cold agglutinin antibodies were detected in the donor's stem cell product. During infusion, the patient developed fever, tachycardia, and hypertension. Despite initial neutrophil engraftment and full donor chimerism, the patient remained transfusion-dependent, indicating PGF. A subsequent CD34-selected stem cell boost from the same donor on Day +108 posttransplant, confirmed to be CAS-negative, resulted in successful platelet engraftment and recovery. This case highlights the potential complications of CAS in donors, emphasizing the need for comprehensive donor evaluation and management strategies to mitigate adverse effects on recipients.