Infections and Immune Reconstitution With Bone Marrow Transplantation in Fanconi Anemia

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Results from a study in which patients with Fanconi anemia underwent a reduced intensity conditioning regimen followed by bone marrow transplantation.
Results from a study in which patients with Fanconi anemia underwent a reduced intensity conditioning regimen followed by bone marrow transplantation.

Results from a study that described immune reconstitution in patients who underwent bone marrow transplantation for Fanconi anemia after being subjected to a reduced intensity conditioning regimen were reported at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.

The 6 patients in this study received a conditioning treatment that included fludarabine 150 mg/m2, cyclophosphamide 20 mg/kg, and rabbit antithymocyte globulin (r-ATG) 20 mg/kg. Bone marrow transplants came from human leukocyte antigen-matched siblings.

Peripheral blood populations of CD19+/CD20+ B cells, CD16+/CD56+ NK cells, CD8+ cytotoxic T lymphocytes, CD3+ T lymphocytes, and CD4+ helper T lymphocytes were measured at 90, 120, 150, 180, 210, and 360 days after treatment. A polymerase chain reaction-based assay was used to identify several possible infections.

Lymphocyte subpopulations recovered in succession with CD16+/CD56+ NK cells first to recover (between 90 to 120 days), CD8+ T lymphocytes recovering next (between 120 and 150 days), followed by CD19+/CD20+ B cells (between 180 and 210 days), and CD4+ T lymphocytes recovering last (beginning at 210 days).

Four patients developed cytomegalovirus infection within 90 days and a fifth patient with chronic graft-vs-host-disease showed BK virus hemorrhagic cystitis and Listeria monocytogenes meningitis at 153 days. The patient was treated with intravenous immunoglobulin, ampicillin, and rifampicin. All patients were reportedly doing well at the time of the presentation.

Immune reconstitution occurred later in this study population than in patients conditioned with lower doses of r-ATG. The authors noted that some lymphocyte subpopulations can respond to viral infections prior to full recovery of CD4+ T lymphocytes, but that early detection and immediate treatment of infections may be crucial.

Reference

1. Lopez-Hernandez G, Lopez-Santiago N, Olaya-Vargas A, et al. Late immune reconstitution and its relationship with infections in patients with Fanconi anemia and bone marrow transplantation. Poster presentation at: 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 4571.

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