Lymphoproliferative Disorders and Infection Risk

Patients with chronic lymphocytic leukemia (CLL) frequently develop hypogammaglobulinemia, leading to increased susceptibility to encapsulated bacteria, principally Streptococcus pneumoniae, with recurrent sinopulmonary infections and septicemia 1, 2
Multiple myeloma patients are functionally hypogammaglobulinemic despite elevated total immunoglobulin levels, because the repertoire of antibody production is severely restricted 1, 2
T-cell exhaustion occurs in LPD, particularly CLL, where CD8+ T cells exhibit features of dysfunction and impaired functionality 3
Lymphoproliferative malignancies cause infiltration of the bone marrow with malignant cells, resulting in leukopenia and dysfunctional marrow production of normal immune cells 1, 2

Patients with advanced or refractory LPD receiving multiple chemotherapeutic regimens face dramatically increased infection risk—nearly 90% of heavily pretreated patients (median 3 prior regimens) with fludarabine-refractory CLL experience serious infectious complications requiring hospitalization 1, 2
Prior treatment with rituximab and fludarabine emerged as specific risk factors for viral infections (OR 1.8, 95% CI 1.05-3.3 for previous rituximab) 3
Refractory hematologic malignancies develop marrow failure from both the underlying disease and cumulative effects of multiple lines of cytotoxic or immunosuppressive therapy 1, 2

Spectrum of Infectious Pathogens

Bacterial pathogens account for 54% of severe infections in LPD patients, with encapsulated organisms (S. pneumoniae, H. influenzae) predominating early in disease course 1, 2
Staphylococcus aureus and gram-negative pathogens occur more commonly in advanced disease and during neutropenia 1, 2
Heavily pretreated LPD patients develop infections from bacterial, viral (HSV, VZV, CMV), fungal, and opportunistic pathogens including Pneumocystis jirovecii 1, 2

The mortality rate for COVID-19 in hematologic malignancies, particularly lymphoproliferative disorders like NHL, CLL, and multiple myeloma, ranged from 13.8% to 37% during the first pandemic wave 6

Do not underestimate infection risk in patients who appear to be responding to therapy—even patients experiencing disease response remain at elevated risk due to persistent immune dysfunction 1, 2