Impact of Chemotherapy on Immunological Parameters in HIV associated Malignancies

Suresh, S (2011) Impact of Chemotherapy on Immunological Parameters in HIV associated Malignancies. Diploma thesis, Christian Medical College, Vellore.


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INTRODUCTION: There are about 2.5 to 3 million HIV patients in India and the calculated prevalence in Tamilnadu is about 0.34 percent. Survival of HIV patients has improved significantly with better control of opportunistic infections and administration of Highly Active Anti-Retroviral Therapy (HAART). Real incidence of AIDS-associated cancers in Indians is not known. There are only few reports in Indian literature. It may be roughly 3-4 per cent in Indians. Since the onset of the HIV/AIDS pandemic in the early 1980s, HIV infection and cancer have been closely related. Several reasons explain this phenomenon; the immune suppression induced by HIV favors occurrence of cancers such as high-grade non - Hodgkin’s lymphoma (NHL); the oncogenic nature of certain viruses, which directly cause cancers such as HHV8 and Kaposi’s sarcoma (KS) and human papilloma virus and cervical cancer in women or rectal squamous cell cancer in men. Because many of these tumors have such a high prevalence in HIV-infected persons, they are included as part of the clinical definition of AIDS and are reported formally as “AIDS-defining malignancies”. Secondly, the increase in survival of HIV-infected patients has led to the observation in several cohort studies that an increasing number of “non-AIDS-defining malignancies”, such as Hodgkin’s disease (HD), invasive anal carcinoma, lung carcinoma, skin cancer and hepatocarcinoma, are now being reported at higher than expected frequencies compared to rates observed in the general population. The hallmark of HIV disease is a profound immunodeficiency resulting primarily from a progressive quantitative and qualitative deficiency of the subset of T lymphocytes referred to as helper T cells. This subset of T cells is defined phenotypically by the presence on its surface of the CD4 molecule which serves as the primary cellular receptor for HIV. It has been observed that malignancies may be related to two different profiles: time spent with a low CD4 cell count and exposure to a high viral load. Both conditions are associated with a higher risk for developing AIDS-related cancers while the time spent with CD4 counts under 500cells/mm3 or with viral load greater than 500 copies/ml are associated with a higher risk for non-AIDS-defining malignancies. AIM OF THE STUDY: To evaluate the impact of chemotherapy and HAART on immunological parameters in all HIV associated malignancies. 1. To describe the response after each cycle of chemotherapy and HAART with reference to CD4 count. 2. To study the pattern of HIV patients presenting with AIDS defining cancers and non-AIDS defining cancers. 3. To determine the feasibility of treatment delivery, patient tolerance, and acute toxicities. MATERIALS AND METHODS: 1. Conditions for patient eligibility: Pathologically (histologic or cytologic) proven diagnosis of primary solid or hematological malignancy and metastasis of unknown origin. 2. Serologic proof of HIV (ELISA/TRIPLE RAPID TEST). 3. All Stages of malignancy based upon the following minimum diagnostic work-up: • History / physical examination within 4 weeks prior to registration. • Imaging work-up with chest roentogram, usg –abdomen/ pelvis/scrotum within 4 weeks prior to registration. • Chest/abdomen/brain/whole neck –CT or MRI wherever feasible within 4 weeks prior to registration. • ECG/ECHOCARDIOGRAM within a week prior to registration. • Endoscopy –upper or lower GI Scopy, Bronchoscopy whenever necessary within 4 weeks prior to registration. • Peripheral smear and bone marrow biopsy/smear whenever necessary within a week prior to registration. 4. Zubrod/ ECOG performance status 0-2. 5. Age: Above 10 and below 65. 6. CBC/differential obtained within a week prior to registration on study, with or without bone marrow involvement but with adequate bone marrow function defined as follows: • Absolute neutrophil count (ANC) _>1500 cell/mm3. • Platelets >100000 cells/mm3. . (Note:The use of transfusion or other intervention to achieve platelets >100000/mm3 is acceptable). • Hemoglobin >8.0g/dl. (Note:The use of transfusion or other intervention to achieve Hgb >8.0g/dl is acceptable). 7. Additional laboratory studies obtained within 2 weeks prior to registration on study • Creatinine <1.5mg/dl. • Bilirubin <1.5 x upper limit of normal. • AST <3x upper limit of normal. • Serum pregnancy test for women of childbearing potential. • Serum lactate dehydrogenase (LDH). 8. HBsAG and HBC within 4 weeks prior to registration on study. 9. Patient must provide Signed study-specific consent form prior to study entry. METHODOLGY: All patients referred to our department with known HIV positivity and patients without known HIV status are referred for Elisa/Triple rapid test and are included in our protocol study. All HIV Positive patients are then registered with ART centre and assessed for CD4 count routinely and viral load if possible. This study requires only CD4 count done at the time of registration and at the beginning of next chemotherapy. Staging of HIV infection was done with CD4+ counts. Serum LDH was estimated for evaluation of disease activity. Patient and relatives were given complete information about the nature of both the diseases, further plan of management and complications involved in this. Different treatment options of highly active anti-retroviral therapy (HAART) were discussed with patients. Reverse transcriptase inhibitor (RTI) – or protease inhibitor (PI) based antiretroviral therapy, interaction between chemotherapeutic agents, their toxicities were discussed in detail with the patient and relatives. RESULTS: Between August 2009 and July 2010, 36 patients met the eligibility criteria of the proposed study and were recruited. The total number of patients registered in Medical Oncology department during the same period was 2465. Patients with HIV associated Malignancy constituted about 1.46%. CONCLUSION: In conclusion, we have identified that; 1. The surrogate parameter to assess the immune competence of HIV patients is CD4 count, which is found to be varying with each cycle of chemotherapy. 2. The final response outcome depends on the initial CD4 count, change in CD4 count between chemotherapy cycles, performance status of the patient, pathobiology and aggressiveness of the malignancy and opportunistic infection. 3. Concurrent chemotherapy and HAART has been observed to be feasible in our study. 4. Non AIDS defining Malignancies are increasing in incidence which can be attributed to the increased life expectancy with HAART.

Item Type: Thesis (Diploma)
Uncontrolled Keywords: Impact of Chemotherapy ; Immunological Parameters ; HIV ; associated Malignancies.
Subjects: MEDICAL > Medical Oncology
Depositing User: Kambaraman B
Date Deposited: 09 May 2018 17:52
Last Modified: 09 May 2018 17:52

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