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In the South African setting, HIV-associated Burkitt lymphoma is associated with frequent leukaemic presentation, complex cytogenetic karyotypes, and adverse clinical outcomes

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Abstract

South Africa (SA) has a high prevalence of human immunodeficiency virus (HIV) infection. People living with HIV are at markedly increased risk of developing Burkitt lymphoma (BL), which is characterized by the MYC translocation. There is a paucity of survival data of HIV-associated Burkitt lymphoma/leukaemia (HIV-BL) cases from SA, and the relationship between karyotype and outcomes has not been widely reported. Here we report the clinico-pathological characteristics of a cohort of cytogenetically confirmed HIV-BL cases. A retrospective, descriptive review was conducted of clinico-pathological features of HIV-BL patients newly diagnosed and treated between 2005 and 2014 at our tertiary academic institution in Cape Town. Only HIV-BL patients with cytogenetic evidence of a MYC translocation were included for analysis. A multivariable Cox proportional hazards model assessed the impact of variables on overall survival (OS). Forty-nine patients met inclusion criteria. Their median age was 37 years (IQR 30–43 years) and 57% (n = 28) were females. Their median CD4 count was 240 cells/μl (IQR 103–423 cells/μl). The majority, 61% (n = 30), had leukaemic presentation, and 20% (n = 10) had a complex karyotype on conventional karyotyping. Seventy-seven percent (n = 36) received various protocols of combination intensive chemotherapy, excluding rituximab. Their OS was 64% (95% CI 45–77%) at 6 months, and 34% (95% CI 17–51%) at 5 years. Leukaemic presentation and a complex karyotype gave a 2.7-fold (95% CI 1.0–6.7) and 2.6-fold (95% CI 1.1–6.6) increased risk of mortality respectively, which were statistical significant (p < 0.05). We report 49 newly diagnosed, cytogenetically confirmed HIV-BL patients at our institution over a 10-year period. There was a high proportion of complex karyotypes and leukaemic presentation, which both independently adversely affected survival. This may be due to differences in the pathobiology of HIV-BL that requires further study and could lead to therapeutic advances in this patient group.

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  • 19 February 2020

    The article “In the South African setting, HIV-associated Burkitt lymphoma is associated with frequent leukaemic presentation, complex cytogenetic karyotypes, and adverse clinical outcomes”.

References

  1. Swerdlow SH, Campo E, Pileri SA et al (2016) The 2016 revision to the World Health Organization (WHO) classification of lymphoid neoplasms. Blood. https://doi.org/10.1182/blood-2016-01-643569

  2. Yarchoan R, Uldrick TS (2018) HIV-associated cancers and related diseases. N Engl J Med. https://doi.org/10.1056/NEJMra1615896

  3. Patel M, Philip V, Omar T et al (2015) The impact of human immunodeficiency virus infection (HIV) on lymphoma in South Africa. J Cancer Ther 06(06):530,531. https://doi.org/10.4236/jct.2015.66057

    Article  Google Scholar 

  4. Barta SK, Samuel MS, Xue X et al (2015) Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma. Ann Oncol 26(5):958–966. https://doi.org/10.1093/annonc/mdv036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sissolak G, Seftel M, Uldrick TS et al (2017) Burkitt’s lymphoma and B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma in patients with HIV: outcomes in a South African public hospital. J Glob Oncol 3(3):218–226. https://doi.org/10.1200/JGO.2015.002378

    Article  PubMed  Google Scholar 

  6. Dang CV, Resar LMS, Emison E et al (1999) Function of the c-Myc oncogenic transcription factor. Exp Cell Res 77:63–77

    Article  Google Scholar 

  7. Aukema SM, Theil L, Rohde M, Bauer B, Bradtke J, Burkhardt B, Bonn BR, Claviez A, Gattenlöhner S, Makarova O, Nagel I, Oschlies I, Pott C, Szczepanowski M, Traulsen A, Kluin PM, Klapper W, Siebert R, Murga Penas EM (2015) Sequential karyotyping in Burkitt lymphoma reveals a linear clonal evolution with increase in karyotype complexity and a high frequency of recurrent secondary aberrations. Br J Haematol 170:814–825. https://doi.org/10.1111/bjh.13501

    Article  CAS  PubMed  Google Scholar 

  8. Declaration of Helsinki – Ethical principles for medical research involving human subjects. The World Medical Association. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed September 27, 2019

  9. Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, Fourth edn. IARC, Lyon

  10. Jaffee E, Harris N, VJ SH (2001) World Health Organization classification of tumours of haematopoeitic and lymphoid tissues. IARC Press, Lyon

    Google Scholar 

  11. Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA, Alliance for Clinical Trials In Oncology (ACTION) (2014) Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and leukemia group B study 10 002. Br J Haematol 165(1):102–111. https://doi.org/10.1111/bjh.12736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Van Dongen JJM, Orfao A (2012) EuroFlow: resetting leukemia and lymphoma immunophenotyping. Basis for companion diagnostics and personalized medicine. Leukemia. 26(9):1899–1907. https://doi.org/10.1038/leu.2012.121

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D, UKLG LY06 collaborators (2002) An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt’s lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol 13(8):1264–1274. https://doi.org/10.1093/annonc/mdf253

    Article  CAS  PubMed  Google Scholar 

  14. Thomas DA, Cortes J, O’Brien S et al (1999) Hyper-CVAD program in Burkitt’s-type adult acute lymphoblastic leukemia. J Clin Oncol 17(8):2461–2470. https://doi.org/10.1200/JCO.1999.17.8.2461

    Article  CAS  PubMed  Google Scholar 

  15. Atra A, Gerrard M, Hobson R, Imeson JD, Ashley S, Pinkerton CR (1998) Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin’s lymphoma (B-NHL)--results of the UKCCSG 9003 protocol. Br J Cancer 77(12):2281–2285. https://doi.org/10.1038/bjc.1998.379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Intermesoli T, Rambaldi A, Rossi G, Delaini F, Romani C, Pogliani EM, Pagani C, Angelucci E, Terruzzi E, Levis A, Cassibba V, Mattei D, Gianfaldoni G, Scattolin AM, di Bona E, Oldani E, Parolini M, Gökbuget N, Bassan R (2013) High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program. Haematologica. 98(11):1718–1725. https://doi.org/10.3324/haematol.2013.086827

    Article  PubMed  PubMed Central  Google Scholar 

  17. Meintjes G, Moorhouse MA, Carmona S, Davies N, Dlamini S, van Vuuren C, Manzini T, Mathe M, Moosa Y, Nash J, Nel J, Pakade Y, Woods J, van Zyl G, Conradie F, Venter F (2017) Adult antiretroviral therapy guidelines 2017. South Afr J HIV Med 18(1):1–24. https://doi.org/10.4102/sajhivmed.v18i1.776

    Article  Google Scholar 

  18. Guech-Ongey M, Simard EP, Anderson WF, Engels EA, Bhatia K, Devesa SS, Mbulaiteye SM (2010) AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology? Blood. 116(25):5600–5604. https://doi.org/10.1182/blood-2010-03-275917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Phillips L (2017) Opie J. The utility of bone marrow sampling in the diagnosis and staging of lymphoma in South Africa 2018:1–8. https://doi.org/10.1111/ijlh.12782

    Article  Google Scholar 

  20. Mbulaiteye SM, Anderson WF, Ferlay J, Bhatia K, Chang C, Rosenberg PS, Devesa SS, Parkin DM (2012) Pediatric, elderly, and emerging adult-onset peaks in Burkitt’s lymphoma incidence diagnosed in four continents, excluding Africa. Am J Hematol 87(6):573–578. https://doi.org/10.1002/ajh.23187

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kelemen K, Braziel RM, Gatter K, Bakke TC, Olson S, Fan G (2010) Immunophenotypic variations of Burkitt lymphoma. Am J Clin Pathol 134(1):127–138. https://doi.org/10.1309/AJCP93LJPTRQPDKR

    Article  PubMed  Google Scholar 

  22. Seegmiller AC, Garcia R, Huang R, Maleki A, Karandikar NJ, Chen W (2010) Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas. Mod Pathol 23(7):909–920. https://doi.org/10.1038/modpathol.2010.76

    Article  CAS  PubMed  Google Scholar 

  23. Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A (2003) Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 98(6):1196–1205. https://doi.org/10.1002/cncr.11628

    Article  CAS  PubMed  Google Scholar 

  24. Galicier L, Fieschi C, Borie R et al (2007) Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. https://doi.org/10.1182/blood-2006-10-051771

    Book  Google Scholar 

  25. Pantanowitz L, Carbone A, Dolcetti R (2015) Microenvironment and HIV-related lymphomagenesis. Semin Cancer Biol 34:52–57. https://doi.org/10.1016/j.semcancer.2015.06.002

    Article  PubMed  Google Scholar 

  26. UNAIDS Data 2017.; 2017. http://www.unaids.org/sites/default/files/media_asset/20170720_Data_book_2017_en.pdf

  27. Antel K, Levetan C, Mohamed Z, Louw VJ, Oosthuizen J, Maartens G, Verburgh E (2019) The determinants and impact of diagnostic delay in lymphoma in a TB and HIV endemic setting. BMC Cancer 19(1):384. https://doi.org/10.1186/s12885-019-5586-4

    Article  PubMed  PubMed Central  Google Scholar 

  28. Li S, Bozzo L, Wu Z, Lu W, Romerio F (2010) The HIV-1 matrix protein p17 activates the transcription factors c-Myc and CREB in human B cells. New Microbiol 33:13–24 http://www.newmicrobiologica.org/PUB/allegati_pdf/2010/1/13.pdf.

    PubMed  Google Scholar 

  29. Germini D, Tsfasman T, Klibi M, el-Amine R, Pichugin A, Iarovaia OV, Bilhou-Nabera C, Subra F, Bou Saada Y, Sukhanova A, Boutboul D, Raphaël M, Wiels J, Razin SV, Bury-Moné S, Oksenhendler E, Lipinski M, Vassetzky YS (2017) HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells. Nat Publ Gr 31:2515–2522. https://doi.org/10.1038/leu.2017.106

    Article  CAS  Google Scholar 

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Acknowledgements

Mrs. Daphne Taylor, Cytogenetics Laboratory, National Health Laboratory Service (NHLS), Groote Schuur Hospital (GSH).

Dr. Dharshnee Chetty, Division of Anatomical Pathology, NHLS, GSH.

Clinical staff, Division of Clinical Haematology, UCT and GSH.

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Authors and Affiliations

  1. Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa

    Jessica Opie, Ania Koller & Nicolas Novitzky

  2. Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    Katherine Antel

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Correspondence to Jessica Opie.

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The Human Research Ethics Committee at the University of Cape Town approved the study. All procedures followed were in accordance with institutional and national ethical standards and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was waived in view of the retrospective nature of the study. Confidentiality and anonymity of patient data was maintained throughout.

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The original version of this article was revised: This article was originally published with an Open Access but due to the authors final decision for OA cancellation this correction was created.

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Opie, J., Antel, K., Koller, A. et al. In the South African setting, HIV-associated Burkitt lymphoma is associated with frequent leukaemic presentation, complex cytogenetic karyotypes, and adverse clinical outcomes. Ann Hematol 99, 571–578 (2020). https://doi.org/10.1007/s00277-020-03908-8

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