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Indian Journal of Cancer, Vol. 47, No. 1, January-March, 2010, pp. 6-7 Guest Editorial HIV-associated non-Hodgkin's lymphoma: How much do we know? Dhir AA Professor and Head of the Department of Medicine, Tata Memorial Hospital, Mumbai, India Code Number: cn10003 PMID: 20071782 DOI: 10.4103/0019-509X.58851 Cancer was associated with acquired immunodeficiency syndrome (AIDS) even before the human immunodeficiency virus (HIV) was identified. The Centre for Disease Control and Prevention (CDC) included Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) as AIDS-defining cancers in 1987. [1] HIV-infected patients are at an increased risk for developing both Hodgkin lymphoma and NHL when compared with the general population. The excess of high-grade NHL was first reported in 1984 following the description of NHL in 90 homosexual men with AIDS. [2] The relative risk of NHL among HIV-infected patients is 150-250-fold higher than in the general population. [3] The post highly active antiretroviral therapy (HAART) era has been associated with acceleration in already declining incidence rates of KS in people with HIV and a decline in the incidence rates of NHL. The magnitude of reduction in NHL rates has not been as great as the reduction in rates of KS and of most other opportunistic infections in people with AIDS, and hence it is likely that NHL will comprise an increasing proportion of AIDS-associated illnesses. Does HIV cause cancer? We do not know. It is thought to contribute to the development of malignancies through several mechanisms, such as impaired immune surveillance, dysregulation of cytokine pathways and growth factor production, inability to combat genomic instability, chronic B cell stimulation and imbalance between cellular proliferation and differentiation. AIDS-defining malignancies are associated with oncogenic viruses. NHL is known to be associated with Ebstein Barr virus (EBV), Helicobacter pylori. EBV has been associated with only 20-40% of AIDS-related systemic NHL (S-NHL), suggesting that other oncogenic viruses like Polyomaviruses may play a role in the pathogenesis of HIV-associated NHL. We need to focus on viral pathogenesis, which may lead to new potential targets for therapeutic intervention in these cancers. The introduction of HAART has opened a new perspective in the treatment of HIV-associated malignancies. The improved control of HIV-infected patients has changed the goal from tumor control to cure and new treatment approaches with more potent regimens need to be evaluated to improve survival and quality of life in HIV-NHL. What are the practical problems faced in treating these patients? Treatment with HAART is complicated by potential pharmacokinetic and pharmacodynamic drug interactions. Pharmacokinetic drug interactions are much more common because of the nature of HAART drug metabolism. These complications were seen in the study by Sharma et al. as well. No specific recommendations exist and clinicians must make decisions despite the missing data by applying greater attention to the choice of chemotherapy protocols and the predictive surrogate markers of HIV disease, such as CD4 cell counts and viral load. Attention to supportive care measures is vital in this patient population. The judicious use of hematopoietic stimulants such as G-CSF may help reduce chemotherapy-induced cytopenic complications. All these patients need to receive prophylaxis for Pneumocystis carinii pneumonia, regardless of the CD4 cell count. Different chemotherapy schedules have been tested but there still is disagreement regarding the optimal treatment for patients with HIV-related NHL even in the post-HAART era. [4] The feasibility of combining chemotherapy with antiretroviral therapy was formally explored in several studies involving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) given with HAART. These studies found response rates between 47% and 75%, with a median OS of up to 27 months and Overall survival (O.S.) rates of 58% and 55% at 1 and 2 years, respectively. [5],[6],[7] Other treatment options include regimens with high-dose chemotherapy, low-dose chemotherapy, oral chemotherapy, continuous and infusion regimens and use of novel therapies such as rituximab. Furthermore, the improvement in immune status and life expectancy of HIV patients has encouraged the use of more aggressive therapies for NHL. Nevertheless, the long-term impact of those treatments remains unclear and ongoing trials are actively recruiting patients with this condition. High-dose therapy with autologous stem cell transplantation is increasingly being used for relapsed or refractory disease. India has the second-largest number of HIV/AIDS patients in the world. However, studies performed in the area of HIV-related malignancies are few. [8] With the availability of HAART and treatment and prevention of opportunistic infections, an increase in life expectancy of HIV-infected individuals and an increase in HIV-related malignancies and other chronic diseases is expected in India. There has been an increase in NHL in India, [9] which, at least partly, could be a reflection of the AIDS epidemic. The Tata Memorial Hospital (TMH) study [10] provides the only risk estimates for cancers in HIV-infected persons in India. NHL appears to be the most common type of cancer reported in Indian people living with HIV/AIDS (PHA). In the TMH study, [10] NHL constituted 38% of the cancers seen in the male PHA whereas 2% of the cancers were expected on the basis of all patients in 2002. In female PHA, the proportion of NHL was lower (16%) than in males because cervical cancer was predominant. There are no published data from India regarding clinical profile, treatment and outcome of patients with NHL in HIV-infected patients. The article by Dr. Atul Sharma et al. is the first such data and adds to the information on Indian data on HIV-associated NHL. Most of the trials in AIDS-related lymphomas have been performed in the West, although most of the HIV patients reside in Afica and India. Only one trial has been carried out in Africa and the authors concluded that dose-modified oral chemotherapy is efficacious and has comparable outcome to that in the United States in the pre-highly active antiretroviral therapy setting, has an acceptable safety profile and is practical in sub-Saharan Africa. [11] As the authors suggest, collection of data is important. Multicentric trials must be carried out in India, linking all the regional cancer centers. This will help in defining the epidemiology of the disease in India and improve the treatment offered to this group of patients. Certain subtypes of AIDS NHL, like plasmablastic lymphoma, are known to occur more commonly in India and their biology needs to be studied and the treatment tailored accordingly. References
Copyright 2010 - Indian Journal of Cancer |
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