Understanding and Treating Lymphoma in Adults
Initial Diagnostic Approach
Lymphoma diagnosis requires histological confirmation through excisional lymph node biopsy or core biopsy—fine-needle aspiration is insufficient for proper classification. 1, 2, 3
Essential Diagnostic Steps
Obtain tissue diagnosis first: Excisional lymph node biopsy is mandatory to distinguish between the >90 subtypes of lymphoma and to determine whether the disease is Hodgkin or non-Hodgkin lymphoma. 1, 3
Immunophenotyping is critical: Flow cytometry and immunohistochemistry must identify CD20 expression (for B-cell lymphomas), cyclin D1 (for mantle cell lymphoma), or other specific markers that guide treatment selection. 1, 4
Staging imaging includes: CT scan with iodine contrast of neck, chest, abdomen, and pelvis as the minimum requirement; PET-CT is optional but recommended for accurate staging in fit patients. 1, 2
Bone marrow evaluation: Aspirate and biopsy should be performed to assess extent of involvement, particularly in fit patients. 1, 2
Laboratory workup must include: Complete blood count with differential, LDH (critical prognostic marker), β2-microglobulin, comprehensive metabolic panel for renal/hepatic function, and uric acid to assess tumor lysis risk. 2, 5
Mandatory infectious disease screening: Test for HIV, hepatitis B and C before initiating any treatment, especially anti-CD20 monoclonal antibodies like rituximab, due to reactivation risk. 2, 5, 4
Patient Fitness Assessment
All patients must undergo geriatric assessment or screening (e.g., G-8 questionnaire) to stratify into fit, vulnerable, or terminally ill categories, as this fundamentally determines treatment intensity and goals. 1, 2
Fitness Categories Define Treatment Goals
Fit patients: Can tolerate standard-dose therapy with curative intent; treatment goal is long-term remission or cure. 1
Vulnerable patients: Have high risk for treatment-related toxicity; require dose-adapted regimens with goal of disease control while preserving quality of life. 1
Terminally ill patients: Life expectancy ~3 months; should receive best supportive care only, not anti-lymphoma treatment. 1
Key Assessment Components
Functional status: Evaluate activities of daily living (ADL) and instrumental ADL using standardized instruments, as these predict treatment tolerance. 1, 2
Comorbidity burden: Systematically assess cardiovascular disease, diabetes, chronic kidney disease, pulmonary conditions using tools like CIRS-G (Cumulative Illness Rating Scale for Geriatrics). 1, 2
Geriatric syndromes: Screen for dementia, depression, falls history, frailty, nutritional status, and polypharmacy. 2
Social support: Absence of adequate social support predicts mortality and must be documented. 2
Treatment by Lymphoma Subtype
Diffuse Large B-Cell Lymphoma (DLBCL)
R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard first-line treatment for fit patients and dramatically improves survival without increasing toxicity. 4, 3, 6, 7
For fit patients: Full-dose R-CHOP every 21 days for 6-8 cycles achieves cure in the majority of patients. 3, 6, 7
For vulnerable patients with cardiac comorbidities: Consider dose-reduced R-CHOP or alternative regimens like R-CVP (rituximab, cyclophosphamide, vincristine, prednisone) to reduce anthracycline exposure. 1, 6
For patients >80 years: Dose-attenuated R-CHOP may be appropriate if performance status is good and no severe organ failure exists. 7, 8
Critical caveat: Even patients >80 years can achieve high response rates (84%) despite reduced doses; age alone should not contraindicate treatment. 8
Follicular Lymphoma (FL)
Asymptomatic patients with follicular lymphoma should undergo watch-and-wait strategy regardless of age, as early treatment does not improve survival. 1
For symptomatic patients with mild symptoms: Rituximab monotherapy is preferred as a chemotherapy-free approach. 1
For high tumor burden in fit patients: Bendamustine plus rituximab (BR) is recommended, with dose reduction or fewer cycles if necessary; consider antibacterial/antiviral prophylaxis due to infection risk. 1
Maintenance rituximab: Optional both first-line and in relapse; decision should balance efficacy against infection risk in elderly patients. 1
For relapsed disease: Rituximab/chemotherapy adjusted to fitness level; idelalisib should be used with caution due to toxicity profile. 1
Chronic Lymphocytic Leukemia (CLL)
Screen for Del(17p) and/or TP53 mutations before any treatment, as this determines first-line therapy selection. 1, 2
For fit patients without Del(17p)/TP53mut: Bendamustine plus rituximab (BR) or dose-attenuated FCR (fludarabine, cyclophosphamide, rituximab) are appropriate alternatives to full-dose FCR. 1, 2
For vulnerable patients without Del(17p)/TP53mut: Chlorambucil combined with obinutuzumab (G-CLB), ofatumumab (O-CLB), or rituximab (R-CLB) is the standard approach. 1, 2
For any patient with Del(17p)/TP53mut: Ibrutinib should be used regardless of fitness level, as it is the only effective option for this high-risk group. 1, 2, 4
For relapsed/refractory CLL: Ibrutinib or idelalisib plus rituximab are first-line options irrespective of Del(17p)/TP53mut status. 1
Mantle Cell Lymphoma (MCL)
Histological confirmation must include detection of cyclin D1 overexpression or t(11;14) translocation; in rare cyclin D1-negative cases, SOX11 may identify variants. 1
For fit elderly patients: Intensive chemo-immunotherapy (e.g., R-CHOP or BR) with goal of achieving complete remission and long-term disease control. 1
For vulnerable patients: Dose-adapted regimens such as dose-reduced BR, R-CVP, or R-CLB (rituximab plus chlorambucil) balance efficacy and tolerability. 1
For patients with severe comorbidities: Mild chemo-immunotherapy like R-CLB or PEP-C are appropriate. 1
Critical Treatment Principles
What to Avoid
Never use aggressive polychemotherapy as initial therapy in elderly patients, as it does not improve overall survival and causes serious infections—the primary cause of death in advanced lymphoma. 9
Avoid full-dose intensive regimens in vulnerable patients: These increase treatment-related mortality without survival benefit. 1, 9
Do not rely on age alone: Patients >80 years can tolerate treatment if carefully selected based on fitness assessment, not chronological age. 7, 8
Quality of Life Considerations
Treatment goals must prioritize quality of life and long-lasting remissions with drugs that can be safely used without long-term toxicity, as most lymphoma patients are of advanced age with multiple comorbidities. 1, 9
Quality of life is a prognostic indicator: Poor quality of life predicts shorter survival and should guide treatment intensity decisions. 1
Balance quantity versus quality of life: For vulnerable and terminally ill patients, symptom control and functional independence take precedence over disease response. 1
Monitoring During and After Treatment
Active Treatment Phase
CBC with differential at every treatment cycle: Monitor for bone marrow suppression, infection risk, and treatment response. 5
Metabolic panel regularly: Assess renal/hepatic function and electrolytes, particularly important for detecting tumor lysis syndrome. 5
LDH monitoring: Track as prognostic marker and indicator of disease burden. 5
Surveillance After Remission
First 2 years: CBC with differential every 3 months. 5
Years 3-5: CBC with differential every 6 months. 5
After 5 years: Annual CBC with differential. 5
Cardiac monitoring: If anthracycline-based chemotherapy was used, perform baseline and periodic echocardiography or MUGA scan to assess for cardiotoxicity. 5
Thyroid function: Check TSH at 1,2, and 5 years if neck irradiation was administered. 5
Supportive Care
Vaccination is mandatory: Administer 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine at least 8 weeks later, plus age-appropriate vaccinations, as lymphoma causes immunosuppression. 3
Household contacts: Should be current with immunizations to protect the immunocompromised patient. 3
Infection prophylaxis: Consider antibacterial/antiviral prophylaxis during bendamustine-containing regimens due to high infection risk. 1