Non-Hodgkin Lymphoma

Overview
Epidemiology and Risk Factors
Classification: B-cell vs. T-cell Lymphomas
Diffuse Large B-Cell Lymphoma (DLBCL)
Follicular Lymphoma
Other Indolent and Aggressive Subtypes
Staging and Diagnosis
Treatment Overview
Novel Therapies: CAR-T, Bispecifics
Key Research Papers
Connections
Featured Videos

1. Overview

Non-Hodgkin lymphoma (NHL) is not a single disease but a heterogeneous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment, arising from B cells, T cells, or NK cells (NCI PDQ, indolent B-cell NHL). The National Cancer Institute's SEER program estimates 79,320 new cases and 19,970 deaths in the United States in 2026, 3.8% of all new cancer cases, which places NHL eighth on SEER's list of the most common cancers; about 2.0% of people are diagnosed with NHL during their lifetime, and the 5-year relative survival for 2016–2022 was 74.3%. SEER reports that age-adjusted rates of new cases fell on average 0.6% a year over 2014–2023 and death rates fell 2.4% a year over 2015–2024 (SEER Cancer Stat Facts: NHL).

Two axes organize the subject: the cell of origin (B-cell vs. T-cell/NK-cell) and the clinical tempo. NCI's PDQ summary divides NHL into indolent lymphomas, which have a median survival as long as 20 years but are usually not curable in advanced stages, and aggressive lymphomas, which have a worse short-term prognosis but of which more than 70% can be cured with intensive combination chemotherapy. The most common NHL is diffuse large B-cell lymphoma (DLBCL), about 30% of newly diagnosed cases (NCI PDQ, aggressive B-cell NHL). Follicular lymphoma (FL) makes up 20% of all NHL and as many as 70% of the indolent lymphomas reported in American and European trials. The two illustrate very different situations: DLBCL is treated with curative intent, while in FL watchful waiting (deferring treatment until symptoms appear) remains a standard option.

Treatment of B-cell NHL has changed through the anti-CD20 antibody rituximab added to chemotherapy, targeted oral drugs such as the BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) and the BCL-2 inhibitor venetoclax in specific subtypes, CAR-T cell therapy for relapsed or refractory large B-cell lymphoma, and bispecific antibodies that redirect T cells to kill CD20-positive lymphoma cells.

2. Epidemiology and Risk Factors

SEER reports that NHL is more common in men than in women and among non-Hispanic White people; it is most frequently diagnosed at ages 65–74, with a median age at diagnosis of 68. Burkitt lymphoma typically involves younger patients and is the most common type of NHL in children (NCI PDQ).

Risk factors reported in the research include:

Immune deficiency — a review of altered immunity describes immune deficiency as one of the strongest known risk factors for NHL, whether congenital, iatrogenic or acquired, with risk rising with the degree of deficiency and NHL in the profoundly immune deficient frequently caused by Epstein–Barr virus (EBV). NHL is one of the AIDS-defining cancers. After solid-organ transplantation, lifelong immunosuppression is followed by post-transplant lymphoproliferative disorder in 1% to 3% of recipients (NCI PDQ).
Autoimmune disease — a 2005 meta-analysis of cohort studies found a high NHL risk in primary Sjögren syndrome (standardized incidence ratio 18.8), a moderate risk in systemic lupus erythematosus (7.4) and a lower risk in rheumatoid arthritis (3.9), with marked heterogeneity among studies. Enteropathy-associated T-cell lymphoma is a complication of celiac disease (NCI PDQ).
Chronic infection — many patients with MALT lymphoma have a history of Helicobacter gastritis, and treating H. pylori may resolve most cases of localized gastric involvement (NCI PDQ). In the pooled InterLymph analysis (17,471 cases, 23,096 controls), increased risks with hepatitis C seropositivity were generally restricted to marginal zone lymphoma, Burkitt lymphoma, DLBCL and/or lymphoplasmacytic lymphoma. Adult T-cell leukemia/lymphoma is caused by the retrovirus HTLV-1, endemic to Japan (especially Kyushu), central Africa, the Caribbean and parts of Central and South America, the Middle East and Australia (NCI PDQ).
Pesticide exposure — a meta-analysis of 44 papers on occupational agricultural pesticide exposure found phenoxy herbicides, carbamate and organophosphorus insecticides and lindane positively associated with NHL.

3. Classification: B-Cell vs. T-Cell Lymphomas

The 5th edition of the WHO classification of haematolymphoid tumours (2022) reorganizes lymphoid neoplasms into a hierarchical system of entities. The broad division used by NCI PDQ:

B-cell NHLs — about 85% of NHL cases (NCI PDQ). They include DLBCL, follicular lymphoma, Burkitt lymphoma, marginal zone lymphomas, mantle cell lymphoma, lymphoplasmacytic lymphoma and small lymphocytic lymphoma. Within DLBCL, gene-expression profiling separates a germinal-centre B-cell-like form from an activated B-cell-like form, and the two differ in survival (see below).
T-cell and NK-cell NHLs — less than 15% of NHL cases. NCI PDQ notes that most T-cell subtypes are associated with worse outcomes than B-cell lymphomas. Subtypes include peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large-cell lymphoma (ALCL), mycosis fungoides and Sézary syndrome, adult T-cell leukemia/lymphoma (ATL), and extranodal NK/T-cell lymphoma, nasal type.

4. Diffuse Large B-Cell Lymphoma (DLBCL)

DLBCL is the most common type of NHL, making up 30% of newly diagnosed cases; most patients present with rapidly enlarging masses (NCI PDQ). It is an aggressive lymphoma treated with curative intent. Its molecular heterogeneity has been studied intensively:

Cell of origin: GCB vs. ABC

A 2000 gene-expression profiling study identified two molecularly distinct forms of DLBCL, a germinal-centre B-like and an activated B-like type, and patients with the germinal-centre type had significantly better overall survival. The 2004 Hans algorithm reproduced this split by immunohistochemistry (CD10, BCL6 and MUM1) on 152 cases: 5-year overall survival was 76% in the GCB group and 34% in the non-GCB group. Those patients were treated before rituximab was added to chemotherapy.

Germinal center B-cell (GCB) type — in the Hans study, expression of BCL6 or CD10 was associated with better overall survival.
Activated B-cell (ABC) / non-GCB type — MUM1 expression was associated with worse overall survival, and the non-GCB phenotype was an independent adverse predictor.
MYC and BCL2 rearrangement (“double-hit”; with BCL6 as well, “triple-hit”) — NCI PDQ states that BCL2 plus MYC rearrangement, or dual overexpression, confers a particularly poor prognosis. In a retrospective review of 117 patients with relapsed or refractory DLBCL who had an autologous transplant, 4-year overall survival was 25% with double-hit lymphoma, 61% with double-expressor lymphoma and 70% without these features.

First-line treatment: R-CHOP and Pola-R-CHP

R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) has been the standard first-line regimen for DLBCL for over 20 years (NCI PDQ). It was established by the GELA LNH-98.5 trial: in 399 patients aged 60–80 given eight cycles of CHOP every three weeks with or without rituximab, complete response was 76% vs. 63%, and adding rituximab reduced the risk of treatment failure (risk ratio 0.58) and of death (0.64) PubMed PMID: 11807147. At 10 years, progression-free survival was 36.5% with R-CHOP vs. 20% with CHOP, and overall survival 43.5% vs. 27.6% PubMed PMID: 20548096. The POLARIX report states that only about 60% of patients are cured with R-CHOP.

The POLARIX trial PubMed PMID: 34904799 randomized 879 patients with previously untreated intermediate- or high-risk DLBCL to six cycles of Pola-R-CHP (polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, replacing vincristine) or R-CHOP. At a median 28.2 months, 2-year progression-free survival was 76.7% vs. 70.2% (hazard ratio 0.73, P = 0.02); 2-year overall survival did not differ (88.7% vs. 88.6%), and the safety profile was similar. On April 19, 2023, the FDA approved polatuzumab vedotin with R-CHP for adults with previously untreated DLBCL, not otherwise specified, or high-grade B-cell lymphoma and an International Prognostic Index (IPI) score of 2 or more (FDA). NCI PDQ reports that in POLARIX the progression-free survival hazard ratio was 0.34 for ABC-subtype tumors, with no such benefit seen for GCB-subtype tumors.

Prognostic scoring

The International Prognostic Index (IPI), built in 1993 from 2,031 patients treated with doxorubicin-containing chemotherapy, uses age, tumor stage, serum LDH, performance status and the number of extranodal sites; its four risk groups had predicted 5-year survival of 73%, 51%, 43% and 26%. In the R-CHOP era, the British Columbia revised IPI (R-IPI) regrouped the same factors into three groups with 4-year overall survival of 94%, 79% and 55%; the authors note that neither index any longer identifies a group with less than a 50% chance of survival.

5. Follicular Lymphoma

Follicular lymphoma (FL) accounts for as many as 70% of the indolent lymphomas reported in American and European clinical trials. NCI PDQ reports that most patients are aged 50 or older and present with widespread disease; rearrangement of the BCL2 gene is present in more than 90% of patients, and BCL2 overexpression is associated with the inability to eradicate the lymphoma by inhibiting apoptosis. Median survival ranges from 8 to 15 years even in advanced stages, but advanced-stage FL is not cured with current options.

Grading and transformation

FL is graded histologically; NCI PDQ states that grade 3b FL is managed similarly to DLBCL. A long-term concern is histologic transformation to an aggressive lymphoma: in a prospective nonrandomized study cited by NCI PDQ, 379 of 2,652 patients (14%) transformed at a median follow-up of 6.8 years, and median overall survival after transformation was 5 years.

Watchful waiting

NCI PDQ reports that three randomized trials comparing watchful waiting with immediate chemotherapy found no difference in cause-specific or overall survival; the median time to needing therapy was 2 to 3 years, and one-third of patients on watchful waiting never required treatment. The RESORT trial (ECOG E4402) PubMed PMID: 25154829 gave 289 responding patients with low-tumor-burden FL either rituximab maintenance or rituximab re-treatment at progression: median time to treatment failure was 4.3 vs. 3.9 years (P = .54), with a median of 18 vs. 4 rituximab doses and no difference in quality of life; 3-year freedom from cytotoxic therapy was 95% vs. 84%. The authors conclude that re-treatment uses less rituximab with comparable disease control.

Treatment when indicated

When treatment is started, options described in the research include:

Obinutuzumab-based chemotherapy — in the GALLIUM trial PubMed PMID: 28976863, 1,202 patients with previously untreated advanced FL received chemotherapy with obinutuzumab (a glycoengineered type II anti-CD20 antibody) or rituximab, followed by up to 2 years of maintenance with the same antibody. Estimated 3-year progression-free survival was 80.0% vs. 73.3% (hazard ratio 0.66); response rates were similar (88.5% vs. 86.9%), and grade 3–5 adverse events were more frequent with obinutuzumab (74.6% vs. 67.8%).
Rituximab with chemotherapy, and rituximab maintenance — in a 534-patient trial cited by NCI PDQ, R-CHOP, R-FM and R-CVP gave the same 8-year overall survival (83%), with 8-year progression-free survival of 52%, 49% and 42%. In the PRIMA study, 2 years of rituximab maintenance after induction gave a median progression-free survival of 10.5 vs. 4.1 years with observation, with no difference in overall survival.
Lenalidomide + rituximab (R2) — in the RELEVANCE trial of 1,030 previously untreated patients, R2 and rituximab-chemotherapy gave identical 6-year progression-free survival (60% and 59%) (NCI PDQ).

6. Other Indolent and Aggressive Subtypes

Marginal zone lymphomas (MZL)

NCI PDQ describes three forms: nodal marginal zone lymphoma, extranodal MALT lymphoma (mucosa-associated lymphoid tissue: gastrointestinal tract, thyroid, lung, breast, orbit, skin), and splenic MZL, which usually presents with massive splenomegaly. Most MALT lymphomas present at stage I or II, most often in the stomach; after standard antibiotic regimens for H. pylori, 50% of patients show endoscopic resolution of gastric MALT lymphoma at 3 months and others after 12 to 18 months, while the t(11;18) translocation predicts a poor response to antibiotics.

Mantle cell lymphoma (MCL)

MCL is made of CD5- and CD20-positive B cells, most often carrying the t(11;14) translocation that causes cyclin D1 overexpression; most patients have stage III or IV disease, and NCI PDQ describes it as highly responsive to treatment but not curable in most cases. A worse prognosis (median survival 4 to 7 years) is associated with blastoid or pleomorphic variants, Ki-67 of 30% or more, and TP53 variants or deletions. By the 2010s the standard for younger fit patients was R-CHOP/R-DHAP followed by autologous stem cell transplant and rituximab maintenance. In the TRIANGLE trial (870 patients aged 65 or younger, results published in abstract form), adding the BTK inhibitor ibrutinib improved 3-year overall survival, and transplant added toxicity but no efficacy to the ibrutinib-containing regimens. NCI PDQ lists the BTK inhibitors acalabrutinib, zanubrutinib, ibrutinib and pirtobrutinib among MCL treatments.

Burkitt lymphoma

Burkitt lymphoma is characterized by translocation and deregulation of the MYC gene on chromosome 8 and extremely high proliferation rates; patients present with rapidly growing masses and a very high LDH (NCI PDQ). Treatment uses aggressive multidrug regimens with rituximab; regimens modeled on childhood Burkitt treatment have left more than 60% of adults with advanced-stage disease free of disease at 5 years. Patients have a 20% to 30% lifetime risk of central nervous system involvement, and intrathecal prophylaxis is part of induction. For NHL generally, NCI PDQ notes that bulky, extensive lymphadenopathy with raised serum uric acid and LDH carries an increased risk of tumor lysis syndrome.

Peripheral T-cell lymphomas (PTCL)

NCI PDQ reports a 5-year survival of approximately 30% to 40% for PTCL in general, closer to 70% to 80% for ALK-positive ALCL, and worse survival for ALK-negative ALCL, AITL and PTCL-NOS; PTCL-NOS patients with multiple adverse factors have 5-year failure-free and overall survival below 20%. In the ECHELON-2 trial of 452 patients with CD30-positive PTCL (about 70% with ALCL), brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone (A+CHP) gave a median progression-free survival of 48.2 vs. 20.8 months with CHOP (hazard ratio 0.71) PubMed PMID: 30522922; at 5 years, overall survival was 70.1% vs. 61.0% PubMed PMID: 34921960. NCI PDQ describes the evidence for stem-cell-transplant consolidation in first remission as anecdotal (phase II and retrospective studies).

7. Staging and Diagnosis

NCI PDQ states that lymph node biopsies are recommended whenever possible, although immunophenotypic data from fine-needle aspiration or core needle biopsy are sometimes sufficient; because prognosis and treatment depend on histopathology, specimens are reviewed by an experienced hematopathologist. Cell-surface markers and immunoglobulin and T-cell receptor gene rearrangements help with diagnosis.

Staging workup described by NCI PDQ:

PET-CT — fluorine-18 FDG PET can be used for initial staging and, alongside CT, for follow-up after therapy; interim PET after two to four cycles has not given reliable prognostic information.
Bone marrow biopsy — in 130 patients with DLBCL, PET identified all clinically important marrow involvement and marrow biopsy upstaged no one; in 580 patients with FL, adding marrow biopsy to imaging did not improve response assessment. Marrow biopsy is included when the result would change management.
Infection screening — HIV screening in aggressive lymphoma, and hepatitis B and C testing before rituximab and/or chemotherapy; people with resolved hepatitis B infection are at risk of reactivation.
CNS risk — the CNS-IPI (age >60, performance status ≥2, elevated LDH, stage III–IV, more than one extranodal site, kidney or adrenal involvement); four to six of these factors define a high-risk group with a 12% risk of CNS involvement by 2 years.

8. Treatment Overview

Treatment depends on NHL subtype, stage and the patient's fitness. In broad outline, as described in NCI PDQ:

Aggressive B-cell NHLs (DLBCL, Burkitt, grade 3b FL, primary mediastinal B-cell lymphoma) — treated with curative intent using rituximab-containing combination chemotherapy: R-CHOP, Pola-R-CHP (for IPI 2–5), dose-adjusted R-EPOCH in primary mediastinal B-cell lymphoma, or Burkitt-type multidrug regimens.
Indolent B-cell NHLs (FL grades 1–3a, MZL, lymphoplasmacytic) — watchful waiting for asymptomatic patients; rituximab alone or with chemotherapy, R2, obinutuzumab-based regimens and maintenance when treatment is needed.
MCL — chemoimmunotherapy (bendamustine-rituximab, or R-CHOP/R-DHAP in younger fit patients), increasingly combined with BTK inhibitors, with rituximab maintenance.
T-cell lymphomas — doxorubicin-based combinations such as CHOP or CHOEP; brentuximab vedotin with CHP for CD30-positive cases.

For localized DLBCL, a randomized trial of 334 patients with nonbulky stage I–II disease found that adding 40 Gy of radiation after R-CHOP-14 did not change 5-year event-free or overall survival (NCI PDQ).

CNS prophylaxis with intrathecal or high-dose intravenous methotrexate is given to some patients at high risk of CNS relapse, particularly those with testicular involvement. NCI PDQ notes that a retrospective analysis of the German RICOVER studies found intrathecal methotrexate did not reduce CNS disease (with the possible exception of testicular involvement), that five retrospective studies and a network meta-analysis found no reduction in CNS relapse with high-dose methotrexate, and that confirmatory randomized trials are lacking.

9. Novel Therapies: CAR-T and Bispecific Antibodies

A 2011 review states that approximately one-third of patients with DLBCL develop relapsed or refractory disease PubMed PMID: 22160081. For relapsed or refractory large B-cell lymphoma, the older standard was salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant. In the CORAL trial, 3-year event-free survival after salvage was 20% for patients who relapsed within 12 months of diagnosis vs. 45% for later relapse, and 21% vs. 47% with vs. without prior rituximab PubMed PMID: 20660832. Two newer immunotherapy approaches have since been tested in this group.

CAR-T cell therapy

Chimeric antigen receptor T-cell (CAR-T) therapy engineers the patient's own T cells to express a receptor targeting CD19 on malignant B cells. Three CD19-directed products carry FDA indications for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy (FDA: axicabtagene ciloleucel; FDA: tisagenlecleucel; FDA: lisocabtagene maraleucel):

Axicabtagene ciloleucel (axi-cel) — in the ZUMA-1 trial PubMed PMID: 29226797 of 111 patients with refractory large B-cell lymphoma, the objective response rate was 82% and the complete response rate 54%; grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28%. At 5 years, estimated overall survival was 42.6% and disease-specific survival 51.0% PubMed PMID: 36821768.
Tisagenlecleucel (tisa-cel) — in the JULIET trial PubMed PMID: 30501490 of 93 infused adults, the best overall response rate was 52% and the complete response rate 40%. Its FDA indications also include B-cell precursor acute lymphoblastic leukemia in patients up to 25 years of age and relapsed or refractory follicular lymphoma.
Lisocabtagene maraleucel (liso-cel) — in TRANSCEND NHL 001 PubMed PMID: 32888407, 73% of 256 efficacy-evaluable patients responded and 53% had a complete response; grade 3 or worse cytokine release syndrome occurred in 2% and neurological events in 10%.

CAR-T has also been compared with standard salvage chemotherapy plus transplant as second-line treatment in patients whose lymphoma was refractory or relapsed within 12 months. In ZUMA-7 (359 patients) PubMed PMID: 34891224, 24-month event-free survival was 41% with axi-cel vs. 16% with standard care (hazard ratio 0.40), with an interim 2-year overall survival of 61% vs. 52%. In TRANSFORM (184 patients) PubMed PMID: 35717989, median event-free survival was 10.1 months with liso-cel vs. 2.3 months (hazard ratio 0.35) at a median follow-up of 6.2 months. The FDA indications for axi-cel and liso-cel include large B-cell lymphoma refractory to, or relapsing within 12 months of, first-line chemoimmunotherapy.

Bispecific antibodies

Bispecific T-cell-engaging antibodies bind CD20 on lymphoma cells and CD3 on T cells, directing the patient's existing T cells to kill the tumor cells without engineering them:

Epcoritamab (subcutaneous CD3 × CD20) — in the EPCORE NHL-1 dose-expansion cohort PubMed PMID: 36548927 of 157 patients with relapsed or refractory large B-cell lymphoma after at least two prior lines, the overall response rate was 63.1% and the complete response rate 38.9%; cytokine release syndrome occurred in 49.7% (grade 3 in 2.5%). On May 19, 2023 the FDA granted accelerated approval for relapsed or refractory DLBCL after two or more lines, citing an overall response rate of 61% and complete responses in 38% of its 148-patient efficacy population (FDA).
Glofitamab (intravenous CD3 × CD20, fixed duration of 12 cycles after obinutuzumab pretreatment to mitigate cytokine release syndrome) — in a phase 2 study PubMed PMID: 36507690 of 155 patients, 39% had a complete response; cytokine release syndrome occurred in 63% (grade 3 or higher in 4%). On June 15, 2023 the FDA granted accelerated approval after two or more lines of therapy, citing an overall response rate of 56% with 43% complete responses in 132 patients (FDA).

Bispecific antibodies are being investigated in combination with other agents and in earlier lines of therapy.

Key Research Papers

Tilly H, Morschhauser F, Sehn LH, et al. (2022). Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma (POLARIX). N Engl J Med 386:351-363 — PubMed PMID: 34904799
Marcus R, Davies A, Ando K, et al. (2017). Obinutuzumab for the First-Line Treatment of Follicular Lymphoma (GALLIUM). N Engl J Med 377:1331-1344 — PubMed PMID: 28976863
Kahl BS, Hong F, Williams ME, et al. (2014). Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402 (RESORT). J Clin Oncol 32:3096-102 — PubMed PMID: 25154829
Neelapu SS, Locke FL, Bartlett NL, et al. (2017). Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma (ZUMA-1). N Engl J Med 377:2531-2544 — PubMed PMID: 29226797
Schuster SJ, Bishop MR, Tam CS, et al. (2019). Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma (JULIET). N Engl J Med 380:45-56 — PubMed PMID: 30501490
Abramson JS, Palomba ML, Gordon LI, et al. (2020). Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 396:839-852 — PubMed PMID: 32888407
Thieblemont C, Phillips T, Ghesquieres H, et al. (2023). Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial (EPCORE NHL-1). J Clin Oncol 41:2238-2247 — PubMed PMID: 36548927
Horwitz S, O'Connor OA, Pro B, et al. (2022). The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann Oncol 33:288-298 — PubMed PMID: 34921960
Alizadeh AA, Eisen MB, Davis RE, et al. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503-11 — PubMed PMID: 10676951
Hans CP, Weisenburger DD, Greiner TC, et al. (2004). Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275-82 — PubMed PMID: 14504078
Friedberg JW (2011). Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program 2011:498-505 — PubMed PMID: 22160081
Coiffier B, Thieblemont C, Van Den Neste E, et al. (2010). Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood 116:2040-5 — PubMed PMID: 20548096
Coiffier B, Lepage E, Briere J, et al. (2002). CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235-42 — PubMed PMID: 11807147
Neelapu SS, Jacobson CA, Ghobadi A, et al. (2023). Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood 141:2307-2315 — PubMed PMID: 36821768
Locke FL, Miklos DB, Jacobson CA, et al. (2022). Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma (ZUMA-7). N Engl J Med 386:640-654 — PubMed PMID: 34891224
Kamdar M, Solomon SR, Arnason J, et al. (2022). Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet 399:2294-2308 — PubMed PMID: 35717989
Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. (2022). Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med 387:2220-2231 — PubMed PMID: 36507690
Horwitz S, O'Connor OA, Pro B, et al. (2019). Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet 393:229-240 — PubMed PMID: 30522922
Gisselbrecht C, Glass B, Mounier N, et al. (2010). Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era (CORAL). J Clin Oncol 28:4184-90 — PubMed PMID: 20660832
International Non-Hodgkin's Lymphoma Prognostic Factors Project (1993). A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 329:987-94 — PubMed PMID: 8141877
Sehn LH, Berry B, Chhanabhai M, et al. (2007). The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 109:1857-61 — PubMed PMID: 17105812
Alaggio R, Amador C, Anagnostopoulos I, et al. (2022). The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia 36:1720-1748 — PubMed PMID: 35732829
Grulich AE, Vajdic CM, Cozen W (2007). Altered immunity as a risk factor for non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 16:405-8 — PubMed PMID: 17337643
Zintzaras E, Voulgarelis M, Moutsopoulos HM (2005). The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med 165:2337-44 — PubMed PMID: 16287762
Morton LM, Slager SL, Cerhan JR, et al. (2014). Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr 2014:130-44 — PubMed PMID: 25174034
Schinasi L, Leon ME (2014). Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int J Environ Res Public Health 11:4449-527 — PubMed PMID: 24762670
Shiels MS, Pfeiffer RM, Gail MH, et al. (2011). Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 103:753-62 — PubMed PMID: 21483021

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Connections

Hematology
Hodgkin Lymphoma — a distinct lymphoma family; shares staging concepts, PET-CT imaging, and some treatment principles but biologically separate from NHL.
Leukemia — related hematologic malignancy; CLL/SLL bridges the leukemia-lymphoma boundary as the same disease with different presentations.
Oncology — full cancer index on this site.
Autoimmune Disease — autoimmune conditions (Sjögren's, RA, celiac disease) are significant NHL risk factors; some lymphomas arise from chronic immune stimulation.
Gastritis — H. pylori gastritis is the precursor to gastric MALT lymphoma; antibiotic eradication can cure early MALT lymphoma.
Complete Blood Count — CBC detects anemia, lymphocytosis, and cytopenia; initial clue for NHL in many presentations.
All Conditions — complete disease index.
Lymphoma — the parent disease class; NHL is its largest branch.