What are B symptoms in a patient with lymphoma and how are they treated?

B Symptoms in Lymphoma: Definition and Treatment

What Are B Symptoms?

B symptoms in lymphoma consist of three specific constitutional symptoms: unexplained fever >38°C (>101°F), drenching night sweats requiring changing of clothes or bedding, and unexplained weight loss of >10% of body weight within 6 months of diagnosis. 1

Specific Criteria for Each Component:

• Fever: Temperature >38°C (>101°F) that is unexplained by infection or other causes 1
• Night sweats: Drenching sweats severe enough to require changing clothes or bedding—not just feeling warm 1
• Weight loss: Unintentional loss of >10% of body weight within the 6 months preceding diagnosis 1

Common Pitfall to Avoid:

• Pruritus (itching), fatigue, and malaise are NOT considered B symptoms, despite being common in lymphoma patients 2

Clinical Significance and Staging

In Hodgkin lymphoma, B symptoms are incorporated into the Ann Arbor staging system, where each stage (I-IV) is subdivided into "A" (absence of B symptoms) or "B" (presence of B symptoms), directly influencing treatment decisions. 2, 1

• For non-Hodgkin lymphoma, B symptoms do not formally alter staging but serve as critical indicators for treatment initiation and prognostic stratification 2
• B symptoms are more common in Hodgkin lymphoma compared to non-Hodgkin lymphoma, particularly in the bimodal age distribution (young adults and older adults) 1
• The presence of B symptoms indicates systemic involvement and more advanced disease 3

Treatment Implications

When to Initiate Treatment:

B symptoms alone mandate immediate treatment initiation in follicular lymphoma, even in otherwise asymptomatic patients with advanced disease. 2, 1, 4

For Follicular Lymphoma:

• First-line therapy: Obinutuzumab or rituximab combined with CHOP or bendamustine for 6 cycles 4
• B symptoms are one of the key criteria that override the watch-and-wait approach 2
• Other indications for treatment include: symptomatic or life-endangering organ involvement, significant ascites or pleural effusion, rapid lymphoma progression, and hematopoietic impairment due to marrow infiltration 2

For Diffuse Large B-Cell Lymphoma (DLBCL):

• Immediate treatment is required regardless of stage when B symptoms are present 4
• Standard therapy: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) every 21 days for 6-8 cycles 4, 5
• More than 60% of patients can be cured with R-CHOP immunochemotherapy 6

Important Treatment Considerations:

• Hepatitis B screening is mandatory before rituximab: Prophylactic antiviral medication up to 2 years beyond last rituximab exposure is required for hepatitis B positive patients 4
• Tumor lysis syndrome prophylaxis: Essential before initiating chemotherapy in patients with high tumor burden and B symptoms 4
• Extended anti-infectious prophylaxis: Should be considered after bendamustine-containing regimens 4
• Premedication: Methylprednisolone 100 mg IV or equivalent glucocorticoid is recommended 30 minutes prior to rituximab infusion 5

Diagnostic Workup When B Symptoms Present

Excisional lymph node biopsy is mandatory for reliable diagnosis—fine needle aspiration alone is insufficient. 4

Essential Diagnostic Steps:

• PET/CT scan: Gold standard for staging in all patients with suspected lymphoma and B symptoms 4
• Core needle biopsy: Acceptable only when surgical biopsy is impractical or poses excessive risk 4
• Histology: Must follow WHO classification with immunophenotyping 4
• Screening tests: HIV, hepatitis B, and hepatitis C 4
• MRI: Recommended for suspected CNS involvement 4

Critical Pitfall:

When B symptoms appear in a patient with known indolent lymphoma, consider histologic transformation to aggressive lymphoma (requires repeat biopsy), as this occurs in approximately 32% of follicular lymphoma patients during follow-up. 4, 7

Response Monitoring

• Mid-treatment assessment: After 3-4 cycles to evaluate symptom resolution and radiographic response 4
• End-of-treatment evaluation: PET/CT using Deauville criteria 4
• Persistent PET positivity after induction identifies patients with adverse prognosis 4

Prognostic Impact

• B symptoms are independent predictors of worse treatment response and survival in NHL 3, 8
• B symptoms are associated with greater myelosuppression from chemotherapy (increased risk of severe leucopenia OR 1.7, p=0.005; and anemia OR 2.3, p=0.025) 8
• Elevated LDH and β2-microglobulin levels combined with B symptoms indicate particularly unfavorable prognosis 3