Non-Hodgkin Lymphoma

Escalate urgently when the clinical course suggests aggressive NHL: rapidly enlarging adenopathy or extranodal masses, constitutional symptoms, suspected CNS disease, gastrointestinal obstruction, or a Burkitt-like rapidly progressive presentation. Aggressive entities include diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, lymphoblastic lymphoma/leukemia, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas; untreated aggressive disease can cause death within weeks. PubMed+1PubMedNon-Hodgkin Lymphoma - PubMedASHChapter 45: Aggressive non-Hodgkin and Burkitt lymphomas

A slowly waxing and waning nodal course favors an indolent process such as follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, or splenic marginal zone lymphoma, but does not eliminate transformation or clinically consequential extranodal disease. The management question is not merely whether lymphoma is present: determine whether symptoms, site-specific compromise, or biologic tempo requires immediate treatment. BMJ+1BMJNon-Hodgkin lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice USPubMedNon-Hodgkin Lymphoma - PubMed

Localizing symptoms direct the immediate branch of evaluation. Headache or focal neurologic findings raise concern for primary CNS lymphoma; nausea, early satiety, vomiting, abdominal fullness, weight loss, or obstruction symptoms suggest gastrointestinal involvement. These presentations require site-directed imaging and coordinated diagnostic planning rather than routine outpatient surveillance. PubMedPubMedNon-Hodgkin Lymphoma - PubMed

Obtain tissue from the most accessible clinically representative involved site and ensure that morphology and immunophenotyping can be performed. NHL arises from B cells, T cells, or NK cells and encompasses clinically distinct entities; treatment varies by histologic subtype, site of involvement, stage, and symptom severity. BMJ+1BMJNon-Hodgkin lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice USPubMedNon-Hodgkin Lymphoma - PubMed

Request hematopathology review with flow-cytometric immunophenotyping when appropriate. Immunophenotyping improved diagnostic accuracy by approximately 10% to 45% in mantle cell lymphoma, DLBCL, and T-cell lymphomas in a clinical evaluation of lymphoma classification, underscoring why morphologic diagnosis alone may be insufficient for treatment selection. ASHASHA Clinical Evaluation of the International Lymphoma Study Group Classification of Non-Hodgkin's Lymphoma | Blood | American Society of Hematology

Use the pathology result to assign the patient to a therapeutic branch rather than relying on the umbrella diagnosis of NHL. DLBCL is the most common NHL subtype and is aggressive; follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, primary CNS lymphoma, and peripheral T-cell/NK-cell lymphomas have materially different expected tempo, staging needs, and treatment approaches. BMJ+2BMJNon-Hodgkin lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice USPubMedNon-Hodgkin Lymphoma - PubMedPubMedNon-Hodgkin lymphoma - World Cancer Report - NCBI Bookshelf

Use PET/CT for initial staging of FDG-avid lymphomas and for interim or end-of-treatment response assessment within the Lugano framework. PET/CT has prognostic value across multiple FDG-avid NHL categories, including Burkitt, mantle cell, follicular, NK-cell, and T-cell lymphomas. ajnr+1ajnrPET/CT Tumor Response Assessment Criteria into Daily PracticeASCORecommendations for Initial Evaluation, Staging, and Response ...

Use the Deauville 5-point score with PET/CT-based response assessment in FDG-avid disease. In NHL, PET/CT has high negative predictive value, reported at 80% to 100%, but its positive predictive value is lower and variable, reported at 50% to 100%; metabolically active residual lesions therefore warrant confirmation with further imaging or biopsy when the result would trigger a major treatment change. ajnrajnrPET/CT Tumor Response Assessment Criteria into Daily Practice

For non-FDG-avid lymphomas assessed by CT, use Lugano quantitative measurements. Target lymph nodes require a long-axis measurement greater than 1.5 cm, extranodal lesions must measure at least 1.0 cm, and up to six nodal and/or extranodal target lesions are incorporated into bidimensional response measurements. ajnrajnrPET/CT Tumor Response Assessment Criteria into Daily Practice

For aggressive NHL, move from classification to subtype-specific systemic treatment planning without delay. DLBCL is the principal aggressive B-cell branch; R-CHOP has remained the longstanding frontline regimen and successfully treats more than 50% of patients with DLBCL, although refractory disease and relapse remain common. ASCOASCOCAR T-Cell Therapy or Autologous Stem Cell Transplant in Large B-Cell Lymphoma: Achieving Goals, Best Possible Outcomes

For indolent B-cell lymphomas, treatment initiation is driven by symptom severity and clinical impact, not simply by radiographic disease detection. Follicular lymphoma, CLL/SLL, and splenic marginal zone lymphoma may follow a prolonged course, while disease location can create indications for intervention even when systemic symptoms are absent. BMJ+1BMJNon-Hodgkin lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice USPubMedNon-Hodgkin Lymphoma - PubMed

Do not use a single treatment framework across B-cell, T-cell, NK-cell, CNS, and gastrointestinal lymphoma. Primary CNS lymphoma, extranodal gastrointestinal lymphoma, marginal zone subtypes, mantle cell lymphoma, and peripheral T-cell lymphomas require disease-specific planning based on site, pathology, and stage. BMJ+1BMJNon-Hodgkin lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice USASHChapter 23: Non-Hodgkin lymphomas - ASH Publications

During observation of indolent disease, reassess at each visit for new constitutional symptoms, accelerating adenopathy, extranodal symptoms, splenic or abdominal symptoms, and declining functional status. A change from a prolonged waxing-and-waning course to a rapidly progressive systemic illness should prompt repeat tissue evaluation for a more aggressive lymphoma component rather than automatic continuation of an indolent-lymphoma plan. BMJ+1BMJNon-Hodgkin lymphoma - Symptoms, diagnosis and treatment | BMJ Best Practice USPubMedNon-Hodgkin Lymphoma - PubMed

After treatment of FDG-avid NHL, compare interim and end-of-treatment PET/CT results with baseline imaging using Lugano/Deauville interpretation. A metabolically inactive result carries favorable prognostic information, while isolated or equivocal residual uptake should be investigated with repeat imaging or biopsy when confirmation would determine salvage therapy, radiation, transplantation, or cellular therapy. ajnrajnrPET/CT Tumor Response Assessment Criteria into Daily Practice

In patients receiving CAR T-cell therapy, monitor actively for cytokine release syndrome and tumor lysis syndrome. Because cellular-therapy trials enrolled patients with high-risk chemorefractory disease and commonly used bridging treatment, transition planning should include toxicity surveillance and reassessment of lymphoma control after infusion. Wolters Kluwer+2Wolters KluwerRenal outcomes after chimeric antigen receptor...ASCOChimeric Antigen Receptor T-Cell Therapy and Bispecific Antibody Use in Earlier Lines of Treatment of Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell LymphomaASCOCAR T-Cell Therapy or Autologous Stem Cell Transplant in Large B-Cell Lymphoma: Achieving Goals, Best Possible Outcomes