What is non-Hodgkin lymphoma?

Non-Hodgkin lymphoma (NHL) encompasses a diverse group of over 60 distinct lymphoid malignancies — cancers of B cells, T cells or NK cells — that do not include Hodgkin lymphoma (HL, which has distinctive Reed-Sternberg cells). NHL ranges from highly aggressive (DLBCL, Burkitt — requiring immediate treatment) to indolent (follicular, marginal zone — often managed with watch-and-wait initially). It is the most common blood cancer globally, causing 544,000 new cases per year.

What are the main NHL subtypes?

B-cell NHLs (approximately 85%): DLBCL (31% of all NHL — most common aggressive); follicular lymphoma (22% — most common indolent); marginal zone lymphoma (8%); mantle cell lymphoma (6% — intermediate); Burkitt lymphoma; primary mediastinal B-cell lymphoma; and many others. T-cell and NK-cell NHLs (approximately 12-15%): peripheral T-cell lymphoma NOS; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma — generally worse prognosis than B-cell NHLs. WHO 5th edition classification (2022) provides the definitive framework.

How is DLBCL treated?

Standard first-line: R-CHOP × 6 cycles (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisolone), achieving cure in approximately 60-70% of patients. Higher-risk molecular subtypes (double-hit/triple-hit DLBCL — concurrent MYC + BCL2 and/or BCL6 rearrangements): intensified regimens (da-EPOCH-R, polatuzumab vedotin + R-CHP — POLARIX trial). Relapsed/refractory DLBCL: second-line chemotherapy for transplant candidates; CAR-T cell therapy (now moving to second-line in transplant-ineligible or early relapse — TRANSFORM, ZUMA-7 trials show superior outcomes to standard second-line).

What is follicular lymphoma?

Follicular lymphoma (FL) is the most common indolent NHL — typically presenting with painless lymphadenopathy, often widespread. Driven by the t(14;18) translocation (BCL2/IGH). Most patients have a waxing-waning course over many years, responding repeatedly to treatment — but FL is rarely cured with conventional therapy. Low-burden asymptomatic FL: watch-and-wait (does not shorten survival). High-burden symptomatic FL: rituximab ± chemotherapy (R-CHOP, R-bendamustine), followed by rituximab maintenance. Novel approaches: obinutuzumab, lenalidomide + rituximab, EZH2 inhibitor (tazemetostat for EZH2-mutated FL).

Is NHL related to HIV?

Yes — HIV dramatically increases NHL risk. HIV-associated NHLs include: DLBCL (most common; occurs at any CD4 count); Burkitt lymphoma (typically at higher CD4 counts, associated with EBV); primary CNS lymphoma (at very low CD4 — strongly associated with EBV); and primary effusion lymphoma. NHL is an AIDS-defining malignancy. Modern ART has dramatically reduced the incidence of HIV-associated NHL, but risk remains elevated above the general population. Treatment is similar to HIV-negative NHL, combined with ART.

Most NHL has no identifiable single cause. Risk factors: immunosuppression (HIV, organ transplant — dramatically increases risk); autoimmune diseases (Sjögren's, RA, Hashimoto's — especially MALT lymphoma at affected sites); prior chemotherapy/radiotherapy; specific infections (H. pylori → gastric MALT lymphoma; EBV → Burkitt; HTLV-1 → adult T-cell lymphoma; HCV → splenic marginal zone lymphoma); hereditary immunodeficiency; and chemical exposures (pesticides, benzene). Most DLBCL is de novo without clear precipitant.

How does GMJ News cover NHL?

GMJ News covers GLOBOCAN NHL data, R-CHOP evidence, CAR-T approvals and access, HIV-associated NHL, follicular lymphoma management and the WHO lymphoma classification. NHL is a major haematological oncology topic — directly relevant to PHIG's cancer programme and the Georgian Medical Journal.

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Non-Hodgkin Lymphoma

Q: What is CAR-T and which lymphomas is it approved for?

CAR-T cell therapy for NHL involves engineering the patient's T-cells to target CD19 (expressed on B-cells) — producing potent and durable anti-tumour responses. Three anti-CD19 CAR-T products are approved for relapsed/refractory large B-cell lymphoma: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah) and lisocabtagene maraleucel (Breyanzi). Two trials (ZUMA-7, TRANSFORM) showed superior outcomes with CAR-T vs standard salvage chemo + autologous HSCT in early R/R DLBCL — moving CAR-T to second-line. Long-term remission in approximately 40-65%.

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Non-Hodgkin lymphoma (NHL) — comprising over 60 distinct B-cell and T-cell lymphoma subtypes — caused 544,352 new cases and 259,793 deaths in 2020, making it the most common blood cancer globally and the seventh most common cancer overall (IARC GLOBOCAN 2020). Diffuse large B-cell lymphoma (DLBCL) — the most common aggressive subtype — is treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone), achieving cure in approximately 60-70% of patients. CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel) have revolutionised treatment of relapsed/refractory DLBCL.

Key messages

544K cases — most common blood cancer

Non-Hodgkin lymphoma caused 544,352 new cases and 259,793 deaths in 2020 — the most common blood cancer and 7th most common cancer globally (IARC GLOBOCAN 2020).

60+ distinct subtypes

NHL encompasses over 60 distinct B-cell and T-cell subtypes with vastly different biology, behaviour and treatment. The WHO classification — based on cell of origin, molecular profile and clinical behaviour — is essential for correct management.

R-CHOP remains backbone

R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone) — introduced in 2001 — remains the standard first-line treatment for DLBCL, achieving cure in approximately 60-70% of patients.

CAR-T transforms relapsed DLBCL

CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel) approved for relapsed/refractory DLBCL achieve approximately 40-65% long-term remission — previously uniformly fatal after 2 lines of chemotherapy.

HIV-associated lymphoma

HIV dramatically increases NHL risk — particularly DLBCL, Burkitt lymphoma and primary CNS lymphoma. NHL is an AIDS-defining illness; modern ART reduces but does not eliminate the excess lymphoma risk.

Follicular lymphoma — indolent but incurable

Follicular lymphoma (FL) — the most common indolent NHL — typically responds repeatedly to treatment but is rarely cured. Watch-and-wait for asymptomatic low-burden FL; rituximab-based therapy for symptomatic disease.

Key statistics

544K

new NHL cases/year (2020)

IARC GLOBOCAN

260K

NHL deaths/year (2020)

IARC GLOBOCAN

60+

distinct NHL subtypes (WHO classification)

WHO

60-70%

DLBCL cure rate with R-CHOP

ESMO/ASH

40-65%

long-term remission with CAR-T in R/R DLBCL

FDA/ASH

most common cancer globally

GLOBOCAN 2020

NHL subtypes by frequency — WHO Classification of Haematological Tumours

Source: WHO Classification 5th edition 2022. DLBCL is the most common aggressive; FL most common indolent.

Glossary of key terms

Diffuse large B-cell lymphoma (DLBCL)
WHO/ESMOThe most common aggressive NHL — a large B-cell lymphoma with diffuse growth pattern and rapid doubling time. Treated with R-CHOP (6 cycles); cure rate 60-70%. High-risk features (IPI score, double-hit/triple-hit molecular biology) may require intensified therapy.

Follicular lymphoma (FL)
WHO/ESMOThe most common indolent NHL — a germinal centre B-cell lymphoma with BCL2/IGH translocation t(14;18). Typically responds repeatedly to treatment; rarely cured with conventional therapy. Watch-and-wait for low-burden asymptomatic disease.

Rituximab (anti-CD20)
FDA/WHO EMLA chimeric anti-CD20 monoclonal antibody — the first approved therapeutic antibody for cancer (1997). Added to CHOP chemotherapy for B-cell NHL → R-CHOP. Also used for maintenance in FL. On WHO Essential Medicines List. Second-generation: obinutuzumab (glycoengineered, superior in CLL).

DLBCL molecular subtypes
WHO/ResearchDLBCL is molecularly heterogeneous: germinal centre B-cell (GCB) type — better prognosis with R-CHOP; activated B-cell (ABC) type — worse prognosis; double-hit (concurrent MYC + BCL2 or BCL6 rearrangement) — highest risk, may require intensified regimens (da-EPOCH-R, polatuzumab-R-CHP).

Burkitt lymphoma
WHOA highly aggressive B-cell NHL — the fastest-growing human tumour (doubling time 24-48 hours). Endemic in tropical Africa (jaw tumours in children — associated with EBV + malaria co-exposure), sporadic (in HIV), and immunodeficiency-associated. Treated with intensive short-duration chemotherapy; highly curable in children.

CAR-T in NHL
FDA/EMAThree anti-CD19 CAR-T therapies approved for R/R large B-cell lymphoma (3rd line+): axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), lisocabtagene maraleucel (Breyanzi). Long-term remission in approximately 40-65% — transformative in a population with previously poor prognosis.