The Impact of Human Immunodeficiency Virus Infection (HIV) on Lymphoma in South Africa

Moosa Patel^1*, Vinitha Philip¹, Tanvier Omar², Dianne Turton³, Geoff Candy⁴, Atul Lakha¹, Sugeshnee Pather²

¹Clinical Haematology Unit, Department of Medicine, Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa.
²Department of Anatomical Pathology, National Health Laboratory Services (NHLS), Johannesburg, South Africa.
³Ampath Laboratories, Johannesburg (Previously, Department of Anatomical Pathology, NHLS), South Africa.
⁴Department of Surgery, University of the Witwatersrand, Johannesburg, South Africa, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

DOI: 10.4236/jct.2015.66057                

Abstract

Human immunodeficiency virus (HIV) infection is endemic in South Africa. Non-Hodgkin lymphoma (NHL) occurs with increased frequency in HIV seropositive individuals. The increase in NHL has been more marked in the last decade, with HIV being the major contributor to this increase. More than 70% of the adult NHL patients at Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, are HIV seropositive. In addition, HIV has impacted on the clinical presentation—being more aggressive and atypical. Histologically, HIV-NHL typically manifests as B-cell, high grade lymphomas, including diffuse large B-cell lymphoma (DLBCL); Burkitt lymphoma (BL); B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL and plasmablastic lymphoma. The latter two entities, which were previously rare or unknown, have gained prominence in the last decade, occurring primarily in HIV seropositive individuals. HIV-NHL, being associated with all these adverse prognostic factors results in a poorer overall survival.

Keywords

Human Immunodeficiency Virus (HIV), Non-Hodgkin Lymphoma (NHL), South Africa, High Grade, Adverse Prognostic Factors, Poorer Overall Survival

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Shisana, O., Rehle, T., Simbeyi, L.C., et al. (2012) South African National HIV Prevalence, Incidence and Behaviour Survey. HSRC Press, Cape Town, 2014.
[2]	Foon, K.A., Ghobrial, I., Geskin, L.J., et al. (2006) The Non-Hodgkin Lymphomas. In: Lichtman, M.A., Beutler, E., Kipps, T.J., Seligsohn, U., Kaushansky, K. and Prchal, J.T., Eds., Williams Hematology, 7th Edition, McGraw Hill, New York, 1407-1459.
[3]	Ziegler, J.L., Beckstead, J.A., Volberding, P.A., et al. (1984) Non-Hodgkin’s Lymphoma in 90 Homosexual Men: Relation to Generalised Lymphadenopathy and the Acquired Immunodeficiency Syndrome. The New England Journal of Medicine, 311, 565-570. http://dx.doi.org/10.1056/NEJM198408303110904
[4]	Spina, M., Carbone, A., Gloghini, A., et al. (2011) Hodgkin’s Disease in Patients with HIV Infection. Advances in Hematology, 2011, Article ID: 402682. http://dx.doi.org/10.1155/2011/402682
[5]	Patel, M., Philip, V. and Fazel, F. (2011) Human Immunodeficiency Virus Infection and Hodgkin’s Lymphoma in South Africa—An Emerging Problem. Advances in Hematology, 2011, Article ID: 578163. http://dx.doi.org/10.1155/2011/578163
[6]	Ulrickson, M., Press, O.W. and Casper, C. (2012) Epidemiology, Diagnosis, and Treatment of HIV-Associated Non-Hodgkin’s Lymphoma in Resource Limited Settings. Advances in Hematology, 2012, Article ID: 932658. http://dx.doi.org/10.1155/2012/932658
[7]	Patel, M., Philip, V., Turton D., et al. (2007) The Impact of HIV on Non-Hodgkin’s Lymphoma at Chris Hani Baragwanath Hospital. Haematologica, 92, 273.
[8]	Casper, C. (2011) The Increasing Burden of HIV-Associated Malignancies in Resource-Limited Regions. Annual Review of Medicine, 62, 157-170. http://dx.doi.org/10.1146/annurev-med-050409-103711
[9]	Bernadi, D., Spina, M. and Tirelli, U. (2011) AIDS-Lymphoma. In: Cavalli, F., Armitage, J. and Longo, D., Eds., Annual of Lymphoid Malignancies, Martin Dunitz Ltd., London, 109-116.
[10]	Goedert, J., Cote, T., Virgo, P., et al. (1998) Spectrum of AIDS-Associated Malignant Disorders. Lancet, 351, 1833-1839. http://dx.doi.org/10.1016/S0140-6736(97)09028-4
[11]	Levine, A.M., Li, P., Cheung, T., Tulpule, A., Von Roenn, J., Nathwani, B.N. and Ratner, L. (2000) Chemotherapy Consisting of Doxorubicin, Bleomycin, Vinblastine and Dacarbazine with Granulocyte-Colony-Stimulating-Factor GCSF in HIV Infected Patients with Newly Diagnosed Hodgkin’s Disease: A Prospective, Multi-Institutional AIDS Clinical Trials Group Study (ACTG 149). Journal of Acquired Immune Deficiency Syndromes, 24, 444-450. http://dx.doi.org/10.1097/00126334-200008150-00009
[12]	Clumeck, N., Sonnet, J., Taelman, H., Mascart-Lemone, F., De Bruyere, M., Vandeperre, P., et al. (1984) Acquired Immunodeficiency Syndrome in African Patients. New England Journal of Medicine, 310, 492-497. http://dx.doi.org/10.1056/NEJM198402233100804
[13]	Parkin, D.M., Wabinga, H., Nambooze, S. and Wabwire-Mangen, F. (1999) AIDS-Related Cancers in Africa: Maturation of the Epidemic in Uganda. AIDS, 13, 2563-2570. http://dx.doi.org/10.1097/00002030-199912240-00010
[14]	Adeniji, K.A. and Anjorin, A.S. (2000) Peripheral Lymphadenopathy in Nigeria. African Journal of Medicine and Medical Sciences, 29, 233-237.
[15]	Stein, L., Urban, M.I., O’Connell, D., Yu, X.Q., Beral, V., Newton, R., et al. (2008) The Spectrum of Human Immunodeficiency Virus Associated Cancers in a South African Black Population: Results from a Case-Control Study, 1995-2004. International Journal of Cancer, 122, 2260-2265. http://dx.doi.org/10.1002/ijc.23391
[16]	Parkin, D.M., Ferlay, J., Hamdi-Cherif, M., et al. (2004) Cancer in Africa: Epidemiology and Prevention. International Agency for Research on Cancer, Lyon.
[17]	Tulpule, A. and Levine, A. (1999) AIDS-Related Lymphoma. Blood Reviews, 13, 147-150. http://dx.doi.org/10.1054/blre.1999.0112
[18]	Beral, V., Peterman, T., Berkelman, R. and Jaffe, H. (1991) AIDS-Associated Non-Hodgkin Lymphoma. The Lancet, 337, 805-809. http://dx.doi.org/10.1016/0140-6736(91)92513-2
[19]	Sitas, F., Bezwoda, W.R., Levin, V., Ruff, P., Kew, M.C., Hale, M.J., et al. (1997) Association between Human Immunodeficiency Virus Type 1 Infection and Cancer in the Black Population of Johannesburg and Soweto, South Africa. British Journal of Cancer, 75, 1704-1707. http://dx.doi.org/10.1038/bjc.1997.290
[20]	Sitas, F., Pacella-Norman, R., Carrara, H., Patel, M., Ruff, P., Sur, R., et al. (2000) The Spectrum of HIV-1 Related Cancers in South Africa. International Journal of Cancer, 88, 489-492. http://dx.doi.org/10.1002/1097-0215(20001101)88:3<489::AID-IJC25>3.0.CO;2-Q
[21]	Abayomi, E.A., Somers, A., Grewel, R., Sissolak, G., Bassa, F., Maartens, D., et al. (2011) Impact of the HIV Epidemic and Anti-Retroviral Treatment Policy on Lymphoma Incidence and Subtypes Seen in the Western Cape of South Africa, 2002-2009: Preliminary Findings of the Tygerberg Lymphoma Study Group. Transfusion and Apheresis Science, 44, 161-166. http://dx.doi.org/10.1016/j.transci.2011.01.007
[22]	Parkin, D.M., Nambooze, S., Wabwire-Mangen, E. and Wabinga, H.R. (2010) Changing Cancer Incidence in Kampala, Uganda, 1991-2006. International Journal of Cancer, 126, 1187-1195.
[23]	Patel, M., Philip, V., Lakha, A., et al. (2013) Trends in Non-Hodgkin Lymphoma (NHL) over the Past Two Decades at Chris Hani Baragwanath Academic Hospital (CHBAH). Proceedings of the Haematology Oncology Symposium, Johannesburg, 24-26 October 2013.
[24]	Kaplan, L.D., Abrams, D.I., Feigal, E., McGrath, M., Kahn, J., Neville, P., et al. (1989) AIDS-Associated Non-Hodgkin’s Lymphoma in San Francisco. Journal of the American Medical Association, 261, 719-724. http://dx.doi.org/10.1001/jama.1989.03420050069041
[25]	Mounier, N., Spina, M., Gabarre, J., Raphael, M., Rizzardini, G., Golfier, J.B., et al. (2006) AIDS-Related Non-Hodgkin Lymphoma: Final Analysis of 485 Patients Treated with Risk-Adapted Intensive Chemotherapy. Blood, 107, 3832-3840. http://dx.doi.org/10.1182/blood-2005-09-3600
[26]	Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition, International Agency for Research on Cancer, Lyon.
[27]	Wiggil, T.M., Mayne, E.S. and Willem, P. (2013) Challenges in Lymphoma Diagnosis in HIV Positive Patients in the South African Setting. Transfusion and Apheresis Science, 49, 157-162. http://dx.doi.org/10.1016/j.transci.2013.07.020
[28]	Pather, S., Mohamed, Z., McLeod, H. and Pillay, K. (2013) Large Cell Lymphoma: Correlation of HIV Status and Prognosis with Differentiation Profiles Assessed by Immunophenotyping. Pathology & Oncology Research, 19, 695-705. http://dx.doi.org/10.1007/s12253-013-9632-2
[29]	Chetty, R., Hlatswayo, N., Muc, R., Sabaratnam, R. and Gatter, K. (2003) Plasmablastic Lymphoma in HIV+ Positive Patients: An Expanding Spectrum. Histopathology, 42, 605-609. http://dx.doi.org/10.1046/j.1365-2559.2003.01636.x
[30]	Patel, M. (1994) Haematology. In: Huddle, K. and Dubb, A., Eds., Baragwanath Hospital 50 Years—A Medical Miscellany, Ultra Litho, 173-190.
[31]	Spina, M., Jaeger, U., Sparano, J.A., Talamini, R., Simonelli, C., Michieli, M., et al. (2005) Rituximab plus Infusional Cyclophosphamide, Doxorubicin and Etoposide in HIV-Associated Non-Hodgkin Lymphoma: Pooled Results from 3 Phase 2 Trials. Blood, 105, 1891-1897. http://dx.doi.org/10.1182/blood-2004-08-3300
[32]	Sparano, J.A., Lee, J.Y., Kaplan, L.D., Levine, A.M., Ramos, J.C., Ambinder, R.F., et al. (2010) Rituximab plus Concurrent Infusional EPOCH Chemotherapy Is Highly Active in HIV-Associated B-Cell Non-Hodgkin Lymphoma. Blood, 115, 3008-3016.
[33]	Dunleavy, K., Little, R.F., Pittaluga, S., Grant, N., Wayne, A.S., Carrasquillo, J.A., et al. (2010) The Role of Tumor Histogenesis, FDG-PET, and Short Course EPOCH with Dose Dense Rituximab (SC-EPOCH-RR) in HIV-Associated Diffuse Large B-Cell Lymphoma. Blood, 115, 3017-3024. http://dx.doi.org/10.1182/blood-2009-11-253039
[34]	Krishnan, A., Molina, A., Zaia, J., Smith, D., Vasquez, D., Kogut, N., et al. (2005) Durable Remission with Autologous Stem Cell Transplantation for High-Risk HIV-Associated Lymphomas. Blood, 105, 874-878. http://dx.doi.org/10.1182/blood-2004-04-1532
[35]	Herbst, A.J., Cooke, G.S., Barnighausen, T., KanyKany, A., Tanser, F. and Newell, M.-L. (2009) Adult Mortality and Anti-Retroviral Treatment Rollout in Rural KwaZulu-Natal, South Africa. Bulletin of the World Health Organization, 87, 754-762. http://dx.doi.org/10.2471/BLT.08.058982
[36]	Deeken, J.F., Pantonowitz, L. and Dezube, B.J. (2009) Targeted Therapies to Treat Non-AIDS-Defining Cancers in Patients with HIV on HAART Therapy: Treatment Considerations and Research Outlook. Current Opinion in Oncology, 21, 445-454. http://dx.doi.org/10.1097/CCO.0b013e32832f3e04
[37]	Kluin, P.M., Harris, N.L., Stein, H., et al. (2008) B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma. In: Swerdlow, S.H., Campo, E., Harris, N.L., et al., Eds., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, International Agency for Research on Cancer, Lyon, 265-266.
[38]	Jaffe, E., Stein, H., Swerdlow, S.H., et al. (2008) B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma. In: Swerdlow, S.H., Campo, E., Harris, N.L., et al., Eds., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, International Agency for Research on Cancer, Lyon, 267-268.