Are all malignancies at high risk for fungal infections?

Are All Malignancies at High Risk for Fungal Infections?

No, not all malignancies carry high risk for invasive fungal infections—risk is highly variable and depends primarily on the type of malignancy, degree of immunosuppression, and treatment-related factors. Hematological malignancies, particularly acute leukemias and allogeneic hematopoietic stem cell transplant recipients, represent the highest-risk populations, while most solid tumors carry substantially lower risk unless specific anatomic or treatment-related factors are present 1.

High-Risk Hematological Malignancies

The following hematological malignancies are definitively high-risk for invasive fungal infections:

• Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) receiving intensive chemotherapy carry the highest risk due to prolonged profound neutropenia (>10 days with counts <100/mcL) 1
• Allogeneic HSCT recipients, especially those with graft-versus-host disease (GVHD) requiring corticosteroids 1, 2
• Acute lymphoblastic leukemia (ALL) in adults undergoing intensive chemotherapy, though pediatric ALL carries low risk except for Pneumocystis pneumonia 1
• Refractory or relapsed hematological malignancies after multiple lines of therapy—nearly 90% of heavily pretreated fludarabine-refractory CLL patients experience serious infectious complications 1

Intermediate-Risk Hematological Malignancies

These malignancies have variable risk requiring individualized assessment:

• Chronic lymphocytic leukemia (CLL) has low baseline risk but becomes high-risk with BTK inhibitor therapy (ibrutinib), with IFD incidence of 2-3% 1
• Multiple myeloma shows a biphasic infection pattern—early Streptococcus pneumoniae and Haemophilus influenzae infections, but fungal risk increases with advanced disease, neutropenia, and high-dose corticosteroids 1
• Non-Hodgkin's lymphoma risk varies by treatment intensity and immunosuppression 1
• Hodgkin lymphoma carries low risk (0.5% IFD incidence), and routine antifungal prophylaxis is not recommended 1

Low-Risk Hematological Malignancies

Antifungal prophylaxis is not indicated for:

• Chronic myeloid leukemia (CML) on tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, ponatinib, asciminib) 1
• Philadelphia chromosome-negative myeloproliferative neoplasms, including those on ruxolitinib 1

Solid Tumors: Generally Low Risk

Solid tumors do not inherently carry high fungal infection risk unless specific anatomic or treatment complications occur 1:

• Anatomic factors that increase risk include:

  • Endobronchial tumors causing recurrent postobstructive pneumonias 1
  • Abdominal tumors obstructing genitourinary or hepatobiliary tracts (predisposing to pyelonephritis and cholangitis) 1
  • Tumors with necrotic centers forming infection nidus 1
  • Direct colonic mucosal invasion causing abscess formation 1

• Surgical factors increase risk based on procedure type (esophagectomy and hepatobiliary reconstruction carry highest risk), tumor burden, performance status, and prior therapies 1

Critical Risk Factors Beyond Malignancy Type

The following treatment and host factors determine actual fungal infection risk across all malignancies 1:

Treatment-Related Factors:

• Prolonged neutropenia (>10 days, especially <100/mcL) 1
• High-dose corticosteroids (>0.3 mg/kg/day for >60 days) 1
• T-cell immunosuppressants (cyclosporine, TNF-α blockers, monoclonal antibodies, nucleotide analogues within 90 days) 1
• Total body irradiation causing gastrointestinal damage 1
• Fludarabine with prolonged immunosuppressive effects (months on lymphopoiesis) 1

Host Factors:

• Prior invasive fungal disease 1
• Advanced/refractory malignancy status 1
• Malnutrition 1
• Organ dysfunction 1

Common Pitfalls to Avoid

Do not assume all cancer patients need antifungal prophylaxis—this leads to unnecessary drug exposure, resistance development, and breakthrough infections with resistant organisms 1. The epidemiology has shifted with widespread azole prophylaxis: Aspergillus species have replaced Candida as the most common pathogen, and rare molds (Zygomycetes, Fusarium) have increased 1.

Risk assessment must be dynamic and repeated—reassess at day 15 post-chemotherapy in acute leukemia patients, as delayed marrow recovery may signal occult infection 1.

CAR-T cell recipients require special consideration: use anti-mold prophylaxis only if pre-infusion risk factors (neutropenia, previous IFD, previous allo-HSCT, refractory disease) AND post-infusion factors (CRS/ICANS requiring steroids/tocilizumab, prolonged neutropenia) are present; otherwise, anti-yeast prophylaxis suffices 1.