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Peer-reviewedCC BYHematology, Transfusion and Cell Therapy

INFECTIOUS OUTCOMES IN APLASTIC ANEMIA AFTER IMMUNOSUPPRESSIVE THERAPY: DATA FROM BRAZILIAN AND US COHORTS

  • Willian Walter De França DA COSTA1
  • Luiz Fernando Bazzo CATTO2
  • Luca ARCURI2
  • Mary CZECH2
  • Ruba SHALHOUB3
  • Tania MACHADO2
  • Marilia Bazzo CATTO1
  • Colin O. WU3
  • Neal S. YOUNG2
  • Jennifer CUELLAR-RODRIGUEZ4
  • Bhavisha A. PATEL2
  • Emma M. GROARKE2
1 more authors
  • Rodrigo Tocantins CALADO1
4 affiliations
  1. 1Department of Medical Imaging, Hematology, and Clinical Oncology, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
  2. 2Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, United States
  3. 3Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, United States
  4. 4Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
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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.

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Cite

BibTeXRIS
BibTeX
@article{costa2026infectious,
  title = {{INFECTIOUS OUTCOMES IN APLASTIC ANEMIA AFTER IMMUNOSUPPRESSIVE THERAPY: DATA FROM BRAZILIAN AND US COHORTS}},
  author = {Willian Walter De França DA COSTA and Luiz Fernando Bazzo CATTO and Luca ARCURI and Mary CZECH and Ruba SHALHOUB and Tania MACHADO and Marilia Bazzo CATTO and Colin O. WU and Neal S. YOUNG and Jennifer CUELLAR-RODRIGUEZ and Bhavisha A. PATEL and Emma M. GROARKE and Rodrigo Tocantins CALADO},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.106578},
  url = {https://doi.org/10.1016/j.htct.2026.106578},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - INFECTIOUS OUTCOMES IN APLASTIC ANEMIA AFTER IMMUNOSUPPRESSIVE THERAPY: DATA FROM BRAZILIAN AND US COHORTS
AU  - Willian Walter De França DA COSTA
AU  - Luiz Fernando Bazzo CATTO
AU  - Luca ARCURI
AU  - Mary CZECH
AU  - Ruba SHALHOUB
AU  - Tania MACHADO
AU  - Marilia Bazzo CATTO
AU  - Colin O. WU
AU  - Neal S. YOUNG
AU  - Jennifer CUELLAR-RODRIGUEZ
AU  - Bhavisha A. PATEL
AU  - Emma M. GROARKE
AU  - Rodrigo Tocantins CALADO
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.106578
UR  - https://doi.org/10.1016/j.htct.2026.106578
AB  - 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.
SN  - 2531-1379
SN  - 2531-1387
ER  -