Abstract
Non-Hodgkin lymphomas (NHL) constitute a heterogeneous group of lymphoid neoplasms whose global incidence has increased over the past few decades. Advances in our understanding of their biology have profoundly changed their classification, diagnosis, and therapeutic management. This narrative review aims to synthesize recent data on the epidemiology, pathophysiology, diagnosis, prognosis, and treatment of NHL, with a particular focus on the realities of sub-Saharan Africa. A narrative literature review was conducted using the PubMed, ScienceDirect, and ResearchGate databases. Publications in French and English published between 2015 and 2025 were searched using the keywords: “non-Hodgkin lymphoma,” “NHL,” “epidemiology,” “diagnosis,” “treatment,” and “Africa.” Systematic reviews, meta-analyses, randomized clinical trials, major observational studies, and international guidelines were included. A total of 54 studies were selected. NHLs are characterized by recurrent genetic alterations involving, in particular, MYC, BCL2, BCL6, and TP53, as well as by the activation of oncogenic signaling pathways such as NF-κB and PI3K/AKT/mTOR. Diagnosis relies on histology, immunohistochemistry, and molecular biology techniques, including fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Prognostic scores such as IPI, FLIPI, and MIPI remain widely used. Targeted therapies, bispecific antibodies, antibody-drug conjugates (ADCs), and CAR-T cells have improved survival in high-income countries. In sub-Saharan Africa, limited access to specialized diagnostic tools and innovative treatments remains a major obstacle. Despite recent therapeutic advances, significant disparities persist in the management of NHL. Strengthening diagnostic capabilities, improving access to innovative treatments, and developing international collaborations are essential to improving patient outcomes in sub-Saharan Africa.
References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249.
2. Armitage JO, Gascoyne RD, Lunning MA, Cavalli F. Non-Hodgkin lymphoma. Lancet. 2017;390(10091):298–310.
3. Pan T, Zhang J, Wang X, Song Y. Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease 2021. Exp Hematol Oncol. 2025;14:84.
4. Campo E, Jaffe ES, Cook JR, Quintanilla-Martinez L, Swerdlow SH, Anderson KC, et al. The International Consensus Classification of mature lymphoid neoplasms. Blood. 2022;140(11):1229–1253.
5. Silue Dohoma A, Danho Nanho C, Kouakou B, Meité N, Ndhatz Comoe E, Kamara I et al.Survival of patients with non-Hodgkin’s malignant lymphoma at the Hematology Department of the Yopougon University Teaching Hospital. Health Sci Dis. 2024;25(5). doi:10.5281/hsd.v25i5.5639
6. Tomoka T, Montgomery ND, Powers E, Dhungel BM, Morgan EA, Mulenga M, et al. Lymphoma and Pathology in Sub-Saharan Africa: Current Approaches and Future Directions. Clin Lab Med. 2018;38(1):91-100.
7. Baissa OT, Ben-Shushan T, Paltiel O. Lymphoma in Sub-Saharan Africa: a scoping review of epidemiology, treatment challenges, and patient pathways. Cancer Causes Control. 2025;36(3):199–230.
8. Chamba C, Mbulaiteye SM, Balandya E, Schuh A. Clinical application of circulating cell-free lymphoma DNA for diagnosis of Burkitt lymphoma. Cambridge Prisms Precision Medicine. 2023;1:e24.
9. Lebwaze BM, Bokambandja FL, Kalengayi RM. EBV in aggressive B-cell lymphomas in DRC. Ann Afr Med. 2019;12(3):358–366.
10. Kimani S, Painschab MS, Kaimila B, Kasonkanji E, Zuze T, Tomoka T et al. Safety and efficacy of rituximab in patients with diffuse large B-cell lymphoma in Malawi: a prospective, single-arm, non-randomised phase 1/2 clinical trial. Lancet Glob Health. 2021;9(7):e1008-e1016. doi:10.1016/S2214-109X(21)00181-9.Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396–1407.
11. Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396-1407. doi:10.1056/NEJMoa180144Pasqualucci L, Dalla-Favera R. Genetics of diffuse large B-cell lymphoma. Blood. 2018;131(21):2307–2319.
12. Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA et al. Molecular subtypes of diffuse large B-cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.Nat Med. 2018;24(5):679-690. doi:10.1038/s41591-018-0016-8.
13. Pasqualucci L, Dalla-Favera R. Genetics of diffuse large B-cell lymphoma. Blood. 2018;131(21):2307–2319.
14. Küppers R, Dalla-Favera R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer. 2015;15(5):291–303.
15. Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A et al. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017 Oct 5;171(2):481-494.e15. doi:10.1016/j.cell.2017.09.027
16. Hübschmann D, Kleinheinz K, Wagener R, Bernhart SH, López C, Toprak UH et al. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas. Leukemia. 2021;35(7):2002-2016. Available from: https://doi.org/10.1038/s41375-021-01251-z
17. Casellas R, Basu U, Yewdell WT, Chaudhuri J, Robbiani DF, Di Noia JM. Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity. Nat Rev Immunol. 2016;16(3):164–76. doi:10.1038/nri.2016.2.
18. Lauring MC, Basu U. Somatic hypermutation mechanisms in lymphomagenesis. Curr Opin Genet Dev. 2024;84:102165.
19. Sarkozy C, Traverse-Glehen A, Coiffier B. Double-hit lymphomas. Lancet Oncol. 2015;16:e555–e567.
20. Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, et al. Targeting B-cell receptor signaling with ibrutinib in diffuse large B-cell lymphoma. Nat Med. 2015;21(8):922-926. doi:10.1038/nm.3884.
21. Young RM, Shaffer AL III, Phelan JD, Staudt LM. B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 2015;52(2):77–85. doi:10.1053/j.seminhematol.2015.01.008.
22. Hämmerl L, Colombet M, Rochford R, Ogwang DM, Parkin DM. The burden of Burkitt lymphoma in Africa. Infect Agents Cancer. 2019;14:17. doi:10.1186/s13027-019-0236-7.
23. Redmond LS, Ogwang MD, Kerchan P, Reynolds SJ, Tenge CN, Were PA, et al. Endemic Burkitt lymphoma: a complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya. Malar J. 2020;19(1):239. doi:10.1186/s12936-020-03312-7.
24. Ondzotto Ibatta CI, Bolenga Liboko AF, Galiba Atipo Tsiba FO, Nziengui JV, Elira Dokekia A. Le retard diagnostique au cours de la prise en charge du lymphome au CHU de Brazzaville. Health Sci Dis. 2019;20(3). doi:10.5281/hsd.v20i3.1322.
25. Mpunga T, Clifford GM, Morgan EA, Milner DA Jr, de Martel C, Munyanshongore C et al. Epstein-Barr virus prevalence among subtypes of malignant lymphoma in Rwanda, 2012 to 2018. Int J Cancer. 2022;150(5):753-760. doi:10.1002/ijc.33840.
26. Njiki Bikoï J, Moni Ndedi EDF, Atenguena Okobalemba E, Mbaga DS, Mbongue Mikangue CA, Membangbi AE et al. Seroprevalence of Epstein-Barr virus, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus among patients with non-Hodgkin's lymphoma at the Yaounde General Hospital, Cameroon. Pan Afr Med J. 2022;41:356. doi:10.11604/pamj.2022.41.356.35206.
27. Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128(21):2489-2496. doi:10.1182/blood-2016-05-718528.
28. Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Mueller SP, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. Eur J Nucl Med Mol Imaging. 2022;49(8):2770-2784. doi:10.1007/s00259-022-05705-9.
29. Silkenstedt E, Salles G, Campo E, Dreyling M. B-cell non-Hodgkin lymphomas. Lancet. 2024;403:1791–1807.
30. Patil S, Rajput S, Patil S, Mhaiskar A. B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies. Pathol Res Pract. 2025;271:156036. doi:10.1016/j.prp.2025.156036.
31. Montgomery ND, Liomba NG, Kampani C, Krysiak R, Stanley CC, Tomoka Tet al. Accurate real-time diagnosis of lymphoproliferative disorders in Malawi through clinicopathologic teleconferences: a model for pathology services in sub-Saharan Africa. Am J Clin Pathol. 2016;146(4):423-430. doi:10.1093/ajcp/aqw118.
32. Tomoka T, Montgomery ND, Powers E, Dhungel BM, Morgan EA, Mulenga M et al. Lymphoma and pathology in Sub-Saharan Africa: current approaches and future directions. Clin Lab Med. 2018;38(1):91-100. doi:10.1016/j.cll.2017.10.007.
33. Xiaoyan Li1 · Xin Wang1, Zhang Y. POD24 and prognosis in indolent B-cell lymphomas. Ann Hematol. 2025;104:1427–1442.
34. Diasonama JF, Wameso MTM, Lebwaze BM, Malemba JJK. Hémopathies malignes de l’adulte à Kinshasa : analyse documentaire d’une série de cas de 2011 à 2021. Ann Afr Med 2023; 16 (2): e5087-e5101.
35. M Keita, B Kouakou, I Kamara, YN Atiméré, D Koné, B Moustapha Mahamat et al. Hemopathies malignes en Afrique de l’Ouest. Jaccr Africa. 2024;8(4):205–213.
36. Traoré C, Sanou AF, Somé RO, Sawadogo S, Koulibiac J, Ségrégation V et al. Les lymphomes chez l’adolescent et l’adulte au Centre Hospitalier Universitaire de Bobo-Dioulasso : à propos de 44 cas. Health Sci Dis. 2020;21(10):29-33. doi:10.5281/hsd.v21i10.2336
37. Gonzalez-Barca E. Developing new strategies for relapsed/refractory diffuse large B-cell lymphoma. J Clin Med. 2023;12(23):7376.
38. Sehn LH, Salles G. Diffuse large B-cell lymphoma. N Engl J Med. 2021;384(9):842-858.
39. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56. doi:10.1056/NEJMoa1804980.
40. Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42. doi:10.1016/S1470-2045(18)30864-7
41. Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. doi:10.1016/S1470-2045(21)00591-X.
42. Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331-1342. doi:10.1056/NEJMoa1914347
43. Morschhauser F, Fowler NH, Feugier P, Tilly H, Chaidos A, Huttmann A et al. Mosunetuzumab in relapsed or refractory follicular lymphoma: a multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7.
44. Horwitz SM, O’Connor OA, Pro B, Illidge T, Fanale M, Advani R et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393(10168):229-240. doi:10.1016/S0140-6736(18)32984-2.
45. Strüßmann T, Marks R, Wäsch R. Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Is There Still a Role for Autologous Stem Cell Transplantation in the CAR T-Cell Era? Cancers (Basel). 2024;16(11):1987. doi:10.3390/cancers16111987.
46. Musimar Z, Mpetani M, Abramson JS, Chabner BA, Mohamed Z. Diffuse large B-cell lymphoma treated with R-CHOP in a resource-limited setting in South Africa: a real-world study. Oncologist. 2023;28:e756-e764.
47. Omotoso O, Teibo JO, Atiba FA, Oladimeji T, Paimo OK, Ataya FS et al. Addressing cancer care inequities in sub-Saharan Africa: current challenges and proposed solutions. Int J Equity Health. 2023;22:189. doi:10.1186/s12939-023-01962-y.
48. Ramashia PN, Nkosi PB, Mbonane TP. Barriers to radiotherapy access in sub-Saharan Africa for patients with cancer: a systematic review. Int J Environ Res Public Health. 2024;21(12):1597. doi:10.3390/ijerph21121597.
49. Ogunniyi TJ, Abdulkareem RR, Emiola AR, Bamidele TR, Wazhi GB, Arinde PO et al. Advancing hematopoietic stem cell transplantation (HSCT) in Africa: a pathway to curing hematological disorders. Health Sci Rep. 2025;8:e71464. doi:10.1002/hsr2.71464.
50. Passweg JR, Baldomero H, Chabannon C, Basak GW, de la Cámara R, Corbacioglu S et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021;56(7):1651-1664. doi:10.1038/s41409-021-01227-8.
51. Mezger NCS, Hämmerl L, Griesel M, Seraphin TP, Joko-Fru WY, Feuchtner J et al. Guideline concordance of treatment and outcomes among adult non-Hodgkin lymphoma patients in sub-Saharan Africa: a multinational, population-based cohort. Oncologist. 2023;28(11):e1017-e1030. doi:10.1093/oncolo/oyad157
52. Ekeng BE, Akaba K, Ide C, Oladele R. Opportunistic infections in hematological malignancies. J Clin Sci Res. 2022;11:175–180.
53. Yıldırım M, Kaya V, Demirpençe O, Paydaş S. Gender and DLBCL outcomes with rituximab. Arch Med Sci. 2015;11(4):708–714.
54. Naresh KN, Raphael M, Ayers L, Hurwitz N, Calbi V, Rogena E et al. Lymphomas in sub-Saharan Africa: what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research? Br J Haematol. 2011;154(6):696-703. doi:10.1111/j.1365-2141.2011.08772.x.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright (c) 2026 Diasonama et al.