# A Cold Case: Cold Agglutinin Disease Complicating Stem Cell Transplant

**Authors:** Majed W. Al-Nazer, Sara Alsammerai, Hemalatha G. Rangarajan, Rolla F. Abu-Arja

PMC · DOI: 10.1155/crit/6270387 · Case Reports in Transplantation · 2026-02-24

## TL;DR

A rare case shows how a donor's cold agglutinin disease can cause complications during a stem cell transplant, leading to poor graft function in the recipient.

## Contribution

This paper reports a rare clinical case linking donor cold agglutinin disease to graft infusion complications and poor graft function in a stem cell transplant recipient.

## Key findings

- A donor's cold agglutinin antibodies in the stem cell product caused infusion complications and poor graft function in the recipient.
- A subsequent CD34-selected stem cell boost from a CAS-negative sample led to successful engraftment and recovery.
- The case underscores the importance of donor screening for cold agglutinin disease to prevent recipient complications.

## Abstract

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.

## Linked entities

- **Diseases:** cold agglutinin disease (MONDO:0018922), T-cell acute lymphoblastic leukemia (MONDO:0004963)

## Full-text entities

- **Genes:** HP (haptoglobin) [NCBI Gene 3240] {aka HP2ALPHA2, HPA1S}, CD34 (CD34 molecule) [NCBI Gene 947], ABO (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) [NCBI Gene 28] {aka A3GALNT, A3GALT1, GTA, GTB, NAGAT}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, THPO (thrombopoietin) [NCBI Gene 7066] {aka CAMT2, MGDF, MKCSF, ML, MPLLG, THC9}, BCAR1 (BCAR1 scaffold protein, Cas family member) [NCBI Gene 9564] {aka CAS, CAS1, CASS1, CRKAS, P130Cas}
- **Diseases:** hematopoietic hypoplasia (MESH:C538361), fever (MESH:D005334), VOD (MESH:D006504), Hemolysis (MESH:D006461), leukopenia (MESH:D007970), autoimmune disorder (MESH:D001327), febrile (MESH:D000071072), CMV (MESH:D003586), tachycardia (MESH:D013610), BK viremia (MESH:D014766), acute kidney injury (MESH:D058186), Klebsiella pneumonia (MESH:D007710), malignancies (MESH:D009369), GVHD (MESH:D006086), respiratory infection (MESH:D012141), spastic cerebral palsy (MESH:D002547), blurry vision (MESH:D014786), PRCA (MESH:D012010), Cell (MESH:D002292), hemolytic anemia (MESH:D000743), Crohn's disease (MESH:D003424), T-cell acute lymphoblastic leukemia (MESH:D054218), infection (MESH:D007239), thrombocytopenia (MESH:D013921), bone marrow relapse (MESH:D001855), ALL (MESH:D054198), PGF (MESH:D051799), anemia (MESH:D000740), Clostridium difficile infection (MESH:D003015), Agglutinin (MESH:D000744), hypertension (MESH:D006973), cytopenia (MESH:D006402), leukemia (MESH:D007938)
- **Chemicals:** PEGylated asparaginase (MESH:C042705), cyclophosphamide (MESH:D003520), fludarabine (MESH:C024352), methylprednisolone (MESH:D008775), bilirubin (MESH:D001663), meperidine (MESH:D008614), diphenhydramine (MESH:D004155), trypan blue (MESH:D014343), azithromycin (MESH:D017963), defibrotide (MESH:C036901), acetaminophen (MESH:D000082), Ara-C (MESH:D003561), dexamethasone (MESH:D003907), nelarabine (MESH:C104457), etoposide (MESH:D005047), tacrolimus (MESH:D016559)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Mycoplasmoides pneumoniae (Filterable agent of primary atypical pneumonia, species) [taxon 2104], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12930209/full.md

## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12930209/full.md

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Source: https://tomesphere.com/paper/PMC12930209