{
  "abstract": "Introduction: Infections still represent the major cause of morbidity and mortality after immunosuppression therapy (IST) for immune aplastic anemia (AA). Current recommendations for antimicrobial prophylaxis are supported by very low certainty evidence. We evaluated the epidemiology and clinical impact of post-IST infections in a large multicenter cohort of patients with AA. Methods: We retrospectively analyzed patients with severe/very severe AA (SAA/VSAA) treated with IST (antithymocyte globulin [ATG], cyclosporine, ± eltrombopag [EPAG]) at the University of São Paulo (USP) (n=38), between 2013 and 2025 and compared with a NIH cohort (n=239). Infections were recorded from the first ATG dose until 2 years or a secondary event (relapse, second-line treatment, clonal evolution, or death), whichever occurred earlier. Infections were graded according to CTCAE v6.0, and grade ≥3 were classified as severe infections. Overall survival (OS) at 24 and at 72 months (median follow-up) were estimated by Kaplan-Meier and compared by log-rank test. Results: Median age was 35 years (range, 2–82). Compared with NIH, USP patients had lower rates of VSAA (5.3% vs. 43.1%, p<0.01) and EPAG exposure (28.9% vs. 86.6%, p<0.01). Prophylaxis rates against bacteria, virus, Pneumocystis jirovecii (PCP) and fungi were 0%, 18.4%, 57.9%, and 13.2% at USP, compared to 2.5%, 100%, 91.6%, and 16.3% at the NIH. Overall, 343 infectious episodes occurred in 160/277 patients (58%), of which 266 (78%) were severe, affecting 124 patients (45%). Infection incidence was higher at USP (89.5% vs. 52.7%, p<0.01), including severe infection (86.8% vs. 38,1%; p<0.01), bacterial (65.8% vs. 26.4%, p<0.01) and fungal infections (21.1% vs. 4.6%, p<0.01). Viral infection rates were comparable (18.4% vs. 13.4%, p=0.45). Mold and yeast infections occurred at USP (n=4 and n=3) and NIH (n=3 and n=5), respectively. PCP occurred once in each cohort, despite PCP prophylaxis. Most fungal infections occurred in patients without antifungal prophylaxis (n=16/19) and in those with VSAA (n=11/19). Prophylaxis was not associated with decreased fungal infection risk p=0.92), although patients that received fungal prophylaxis had lower absolute neutrophil counts (ANC) compared to those without (median ANC 0.39 vs. 0.09 cell/µL, p<0.01). Severe infection was associated with inferior OS (p<0.01). At 24 months, OS was 64.2% in patients with ≥3 severe infections versus 98.6% and 97.9% in those with 1–2 or no severe infections, respectively; corresponding 72-month survival was 53.6%, 92.3%, and 92.1%. In multivariable cox regression analysis, severe infections were independently associated with 24-month mortality, independent of age and disease severity (HR, 19.4; p<0.01). In the Brazilian cohort, infection incidence was numerically lower among patients exposed to EPAG (81.8% vs. 92.6%; OR, 0.36; 95% CI, 0.04–2.95; p=0.56). Conclusion: Infections were independently associated with early mortality following IST, with excess risk driven by bacterial and fungal, but not viral, infections. The higher infectious burden observed in the Brazilian cohort may reflect differences in supportive care, antimicrobial prophylaxis strategies, and lower access to EPAG, potentially resulting in prolonged neutropenia after IST.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Imaging, Hematology, and Clinical Oncology, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, SP, Brazil",
    "Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, United States",
    "Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, United States",
    "Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Willian Walter De França DA COSTA"
    },
    {
      "affs": [
        1
      ],
      "name": "Luiz Fernando Bazzo CATTO"
    },
    {
      "affs": [
        1
      ],
      "name": "Luca ARCURI"
    },
    {
      "affs": [
        1
      ],
      "name": "Mary CZECH"
    },
    {
      "affs": [
        2
      ],
      "name": "Ruba SHALHOUB"
    },
    {
      "affs": [
        1
      ],
      "name": "Tania MACHADO"
    },
    {
      "affs": [
        0
      ],
      "name": "Marilia Bazzo CATTO"
    },
    {
      "affs": [
        2
      ],
      "name": "Colin O. WU"
    },
    {
      "affs": [
        1
      ],
      "name": "Neal S. YOUNG"
    },
    {
      "affs": [
        3
      ],
      "name": "Jennifer CUELLAR-RODRIGUEZ"
    },
    {
      "affs": [
        1
      ],
      "name": "Bhavisha A. PATEL"
    },
    {
      "affs": [
        1
      ],
      "name": "Emma M. GROARKE"
    },
    {
      "affs": [
        0
      ],
      "name": "Rodrigo Tocantins CALADO"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ygtf39e58ep4.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.106578",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926003251",
  "id": "5ygtf39e58ep4",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.106578",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2730|Neutropenia and Cancer Infections"
    ]
  ],
  "openalex": "W7223100096",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926003251/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/5ygtf39e58ep4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:33Z",
      "native_id": "8506222b0c5d4b60b752026c12f65943",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.106578"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Neutropenia and Cancer Infections",
      "subfield": "oncology"
    }
  ],
  "title": "INFECTIOUS OUTCOMES IN APLASTIC ANEMIA AFTER IMMUNOSUPPRESSIVE THERAPY: DATA FROM BRAZILIAN AND US COHORTS",
  "title_text": "INFECTIOUS OUTCOMES IN APLASTIC ANEMIA AFTER IMMUNOSUPPRESSIVE THERAPY: DATA FROM BRAZILIAN AND US COHORTS",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:33Z",
  "url": "https://research.draconitic.com/paper/5ygtf39e58ep4",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}