Do patients with lymphoma receiving chemotherapy and immunotherapy develop fever?

Do Patients with Lymphoma Undergoing Chemotherapy and Immunotherapy Develop Fever?

Yes, patients with lymphoma receiving chemotherapy and immunotherapy frequently develop fever, with febrile neutropenia occurring in 27-47% of patients depending on the regimen intensity, patient age, and risk factors. 1

Incidence and Risk Factors

Fever is a common and expected complication in lymphoma patients undergoing treatment:

• Non-Hodgkin's lymphoma patients aged ≥60 years receiving CHOP or similar regimens experience febrile neutropenia in 27-47% of cases, with the highest rates occurring during the first cycle of chemotherapy 1
• The incidence of febrile episodes ranges from 10.8-15.2% per chemotherapy cycle in patients with lymphoma receiving moderately myelosuppressive regimens 2
• Fever may be the only manifestation of infection in neutropenic patients, as the immune response is attenuated during chemotherapy, making clinical signs of inflammation diminished or absent 1, 3

High-Risk Populations

Elderly lymphoma patients face substantially elevated risk:

• Patients over 65 years with aggressive lymphoma have a 34% incidence of neutropenic fever, compared to 21% in younger patients 1
• Hospitalization duration for febrile neutropenia averages 12.1 days in patients ≥65 years versus 8.2 days in younger patients 1
• Infection-related mortality is increased in older lymphoma patients, making prophylactic strategies particularly important in this population 1

Specific Considerations for Immunotherapy

Rituximab-containing regimens add complexity to fever management:

• Patients receiving rituximab with chemotherapy require careful evaluation of rash with fever, as they are at high risk for severe infections including MRSA and require empiric vancomycin plus antipseudomonal coverage 4
• Herpesviridae viral infections occur in 20.16% of lymphoma patients over 5 years of chemotherapy, with risk factors including female sex, cumulative steroid doses ≥2500 mg/m², and history of neutropenic fever 5

Prevention Strategies

Prophylactic approaches reduce but do not eliminate fever risk:

• G-CSF prophylaxis significantly reduces febrile neutropenia in high-risk NHL patients (23-33% with G-CSF versus 44-50% without), though fever still occurs in a substantial proportion 1
• Fluoroquinolone prophylaxis with levofloxacin 500-750 mg daily during expected neutropenia reduces febrile episodes from 15.2% to 10.8% in lymphoma patients 6, 2
• Prophylactic antibiotics are specifically recommended for elderly patients (≥65 years) with aggressive lymphoma receiving curative-intent chemotherapy 1

Critical Clinical Pitfalls

Common management errors to avoid:

• Do not delay empiric broad-spectrum antibiotics while awaiting culture results - fever in neutropenic lymphoma patients is an oncologic emergency requiring antibiotic initiation within 2 hours 4, 3
• Do not assume fever resolution means no infection - continue monitoring for 48-72 hours as bacterial infections can declare later 7
• Do not underestimate innocuous-appearing skin lesions - even small rashes require careful evaluation in neutropenic patients as signs of inflammation are often diminished 4
• Do not overlook opportunistic infections in HIV-positive lymphoma patients - PJP and CMV are more likely causes of fever in this population receiving chemotherapy 1

Expected Clinical Course

Fever patterns follow predictable timelines:

• Most febrile episodes occur after the first course of treatment in elderly NHL patients, with 32% experiencing fever during the initial cycle 1
• The risk of grade IV neutropenia (<0.5 × 10⁹/L) ranges from 20% to >70% depending on regimen intensity, with associated infection risks of 10-50% 8
• Multiple lines of chemotherapy are the main risk factor for severe infections in lymphoma patients with febrile episodes 9