What are the management and follow-up recommendations for a patient with a history of non-Hodgkin lymphoma (NHL)?

Management and Follow-Up of Non-Hodgkin Lymphoma

For patients with a history of treated non-Hodgkin lymphoma in remission, follow-up should consist of clinical history and physical examination every 3 months for the first 2 years, every 6 months for years 3-5, then annually, with complete blood count and LDH at 3,6,12, and 24 months only—routine surveillance imaging is not recommended as it provides no survival benefit and exposes patients to unnecessary radiation. 1, 2

Clinical Surveillance Schedule

The surveillance strategy prioritizes clinical assessment over imaging because most relapses (83%) are detected by patient-reported symptoms or physical examination findings, not by routine scans. 3

Follow-up visit frequency: 1, 2

• Every 3 months during the first 2 years
• Every 6 months during years 3-5
• Annually after 5 years, with lifelong attention to secondary malignancies and late treatment effects

At each visit, specifically assess for: 1

• Development of new adenopathy or masses
• Constitutional symptoms (fever, night sweats, weight loss)
• Signs of secondary malignancies
• Late effects of chemotherapy (neuropathy, cardiac dysfunction)

Laboratory Monitoring

Complete blood count and LDH should be obtained at 3,6,12, and 24 months only. 1, 2 After 24 months, laboratory studies should only be performed when symptoms or clinical findings warrant evaluation in patients who remain candidates for additional therapy. 1

This limited approach is evidence-based: routine laboratory monitoring beyond these intervals in asymptomatic patients has not been shown to improve outcomes and only increases healthcare costs. 3

Radiological Surveillance

Routine surveillance CT or PET scans are explicitly not recommended in asymptomatic patients. 2 The evidence is clear on this point:

• CT imaging may be considered at 6,12, and 24 months, but only if clinically indicated 1
• After 24 months, imaging should only be performed for evaluation of suspicious symptoms or clinical findings 1
• Routine surveillance imaging is ineffective, costly, and exposes patients to radiation that doubles their risk of secondary malignancies 2, 4
• In one study, 44% of patients receiving routine CT surveillance received cumulative radiation doses that significantly increased cancer risk, yet detected zero asymptomatic relapses 4

Treatment-Specific Late Effects Monitoring

Certain patients require additional surveillance based on their treatment exposures:

For patients who received neck/cervical irradiation: 1, 2

• Measure thyroid-stimulating hormone (TSH) at 1,2, and 5 years minimum
• Continue monitoring as clinically indicated thereafter

For women who received thoracic/chest irradiation, especially if under age 25 at treatment: 5, 1, 2

• Clinical breast examination starting from end of treatment
• Annual mammography beginning at age 40-50 years

For patients who received anthracyclines or mediastinal radiation: 2, 6

• Document cumulative anthracycline dose in mg/m²
• Consider echocardiography or MUGA scan to quantify ejection fraction if additional anthracyclines were used or if cardiac symptoms develop
• Maintain cardiovascular surveillance throughout follow-up

When Relapse is Suspected

If clinical findings suggest possible relapse: 2, 6

1. Biopsy is mandatory before initiating any salvage therapy—this is non-negotiable, particularly for relapses occurring >12 months after initial diagnosis 1, 2
2. Perform full restaging workup including:
   • CT chest/abdomen/pelvis or PET/CT 2
   • Complete blood count, comprehensive metabolic panel, LDH, uric acid 2, 6
   • Bone marrow aspirate and biopsy if initially involved 5
   • Consider diagnostic spinal tap with prophylactic intrathecal chemotherapy in high-risk patients (>2 adverse IPI parameters, bone marrow/testis/spine/skull base involvement) 5, 6

Management of Relapsed Disease

For suitable patients (age <65 years, no major organ dysfunction), conventionally-dosed salvage chemotherapy followed by high-dose therapy with autologous stem cell transplantation is the standard approach. 5, 6

Salvage regimen options include R-DHAP, R-ESHAP, R-ICE, or R-EPOCH—no comparative trials demonstrate superiority of one over another, so choice depends on institutional experience. 5, 6

For patients unsuitable for high-dose therapy (elderly, significant comorbidities, HIV-positive), the same salvage regimens may be used at conventional doses, potentially combined with involved field radiotherapy. 5

Critical Pitfalls to Avoid

• Never order routine surveillance imaging in asymptomatic patients—it has no survival benefit and causes harm through radiation exposure and false positives 2, 4
• Never ignore patient-reported symptoms between scheduled visits—these detect the majority of relapses, not routine scans 2, 3
• Never skip long-term monitoring beyond 5 years—the focus appropriately shifts to secondary malignancies and late treatment effects rather than lymphoma relapse 2
• Never forget treatment-specific surveillance for thyroid dysfunction, cardiac toxicity, and secondary breast cancer in appropriate populations 1, 2
• Never initiate salvage therapy without biopsy confirmation—histological verification is mandatory to exclude transformation and guide appropriate treatment 1, 2, 6