Case Report

AIDS-Related Lymphoma: Resolution with Antiretroviral Therapy Alone

Journal of the International Association of Providers of AIDS Care 2014, Vol. 13(4) 313-315 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2325957414521868 jiapac.sagepub.com

Rabih Riad Hallit, MD1, Muhammad Afridi, MD1, Raymund Sison, MD1, Maria Elaine Y. Szabela, MD2, Nikki Bajaj, MD2, Roula Alchaa, MD1, Souheil Hallit, MS, PharmD1, Nelly Awkar, MD3, Jack Boghossian, MD1, and Jihad Slim, MD1

Abstract Patients with HIV are at increased risk of malignancy, particularly lymphoma, which is the most common malignancy leading to death. With the advent of highly active antiretroviral therapy (HAART), patients live longer but have a longer duration of antigenic stimulation, increasing the prevalence of AIDS-related lymphoma (ARL) in the population living with HIV. Highly active antiretroviral therapy plays a direct role in preserving the immune system, helping to decrease the incidence of ARL. We present a case of a female patient with HIV (CD4 count of 576 cells/mm3) diagnosed with a stage III-B non-Hodgkin lymphoma in 2009 while off HAART. She was subsequently started on HAART, leading to full resolution of her lymphoma without any chemotherapeutic intervention. She was last seen in the clinic in December 2013 without any evidence of recurrence of her lymphoma. To our knowledge, this is the first case report of a stage III-B non-Hodgkin lymphoma in an HIV-infected patient, which resolved with only HAART. Keywords HIV, AIDS, HAART, lymphoma

Introduction Patients infected with HIV are at an increased risk of developing malignancies. These neoplasms account for one-third of total deaths in the population living with HIV in which lymphoma is the most common cause.1 Both low CD4 count and continuous antigenic stimulation are responsible for an increased incidence in non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV.2 Prior to the advent of highly active antiretroviral therapy (HAART) in 1996, AIDS-related lymphoma (ARL) was associated with a dismal prognosis, especially in patients with poor performance status, advanced immune dysfunction, and limited hematopoietic reserve. The introduction of HAART is associated with an improved prognosis in patients with HIV who are diagnosed with NHL and significantly reduces the incidence of some types of NHL, notably primary central nervous system lymphoma in patients with extremely low CD4 counts.3 Highly active antiretroviral therapy without the concomitant use of chemotherapy has not been shown to curb aggressively spreading HIV-associated lymphoma. We present the first case report in the literature of a B-cell lymphoma (stage III-B) that resolves with only antiretroviral therapy (ART) in an HIV-infected patient. We present a 55-year-old African American woman with a past medical history of HIV, hypertension, and dyslipidemia. The patient was diagnosed with HIV in 1989, contracted from

intravenous drug use. Over the years, her HIV was well controlled on HAART. However, in 2004, she developed major depressive disorder, at which time she subsequently refused therapy. At that time, her CD4 count was 576 cells/mm3, and she was being followed regularly with periodic measurements of CD4 counts and viral loads while off ART. In February 2009, the patient presented with intermittent low grade fevers, and her physical examination was unremarkable except for the presence of a left axillary lymph node. She subsequently underwent a lymph node biopsy that revealed the presence of a low grade B-cell lymphoma with plasmacytic differentiation and follicular colonization on histologic examination. Her lactate dehydrogenase (LDH) level at that time was 241 units/L. The patient was restarted on ART, specifically darunavir, norvir,

1

Department of Infectious Disease, Saint Michael’s Medical Center, Newark, NJ, USA 2 Department of Internal Medicine, Saint Michael’s Medical Center, Newark, NJ, USA 3 Department of Hematology–Oncology, Saint Michael’s Medical Center, Newark, NJ, USA Corresponding Author: Rabih Riad Hallit, Department of Infectious Disease, Saint Michael’s Medical Center, 100 Hepburn road, Apartment 6-I, Clifton, NJ, 07012, USA. Email: [email protected]

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Journal of the International Association of Providers of AIDS Care 13(4)

abacavir (ABC), and lamivudine (3TC). A positron emission tomography (PET) scan was done, which revealed the presence of moderate metabolic activity within multiple neck, axillary, internal pelvic, and right inguinal lymph nodes. The PET scan also demonstrated a 5-mm ametabolic nodule at the right lung apex with a normal-sized spleen and no osseous lesions. With a lack of lymphoma cells in the bone marrow biopsy, the patient was diagnosed with a stage III-B lymphoma. Due to financial hardships, she was lost to follow-up, however she returned to the clinic a few months later, still taking her ART as prescribed. At this time, she denied any fevers or night sweats, and the left axillary lymph node was not palpable on physical examination. Repeat LDH was 199 units/L. To confirm the lack of progression in this woman with stage III-B lymphoma, a repeat PET scan was done and revealed that the various hypermetabolic lymph nodes demonstrated previously within the neck, axillary, pelvic, and inguinal regions had decreased in size and had become ametabolic. The 5-mm ametabolic nodule at the right lung apex was unchanged. A third PET scan done 10 months after the second scan did not show any evidence of active or recurrent lymphoma and a stable 5-mm nodule in the lung with no enlarged or hypermetabolic lymph nodes was noted; all while her virus load was undetectable on HAART. On her last office visit in December 2013, she was free of any recurrence of the lymphoma and continues to be compliant with her HAART.

Discussion Since the beginning of the AIDS epidemic, the treatment of HIV-related NHL has been a challenge. Considerable progress has been made in the treatment of NHL with a concomitant HIV diagnosis. Highly active antiretroviral therapy has improved the outcome as suggested in clinical trials through immune system modulation and HIV viral suppression. Currently, the standard course of chemotherapy being used is mainly cyclophosphamide, doxorubicin, vincristine, and prednisone; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone; or infusional cyclophosphamide, doxorubicin, and etoposide. Many recent studies have demonstrated that ARL can be treated with standard dose lymphoma protocols without experiencing undue toxicity.4 Histologic comparison in pre-HAART and post-HAART patients with NHL illustrated a higher percentage of intermediate-grade NHLs with a decrease in high-grade NHLs in the post-HAART cohort.1 Several studies have demonstrated that patients with diffuse large B-cell lymphoma or Burkitt lymphoma who are on HAART have comparable outcomes with those of HIV-negative patients treated with the same chemotherapy regimens. In the post-HAART era, the spectrum of cancer in HIV-infected patients shifted from AIDS-defining cancers such as primary Kaposi sarcoma (KS) and NHL to non-AIDSdefining cancers.5 Consequently, HAART equates to an improvement in the immune status, thus reducing the risk of developing lymphoma and when given concomitantly with the standard course of chemotherapy improves survival and reduces chemotherapy-related adverse effects. There is now ample

evidence to indicate that the widespread introduction of HAART has been associated with a marked reduction in KS incidence. In patients with limited cutaneous lesions, an effective HAART regimen is the first step (and possibly the only step) for the treatment of KS. In most cases, KS lesions disappear completely after a few weeks or months.6 Kaposi sarcoma regression with HAART alone has been well documented, with 66% to 86% overall response rate and 35% complete remission rate. It is difficult to establish the exact response rate to HAART among patients with KS, since in many patients with advanced KS cytotoxic chemotherapy has been administered concurrently.7 In our case, the patient was diagnosed with HIV in 1989 and was compliant with HAART until 2004. Subsequently, the patient became noncompliant, and HAART was discontinued in 2004. About 4 years later, the patient developed B-cell symptoms and was diagnosed with NHL stage III-B via axillary lymph node biopsy and restarted on HAART. The patient was again lost to follow-up while she continued her HAART without any chemotherapy. Several months later, the patient reported an absence of her previous symptoms along with repeat PET scans showing remission of the disease. Reevaluation 10 months later confirmed complete remission of the cancer without any signs of infection. During her last visit in December 2013, there was no evidence of recurrence of the disease, and she continues to be compliant with her HAART with regular visits at our clinic. Positron emission tomography scans may be positive in patients with benign HIV-related lymphadenopathy and typically there is minimal uptake in the absence of infections. There was no evidence that our patient had any infectious disease that causes increased uptake. One of the limitations of this case is that we cannot confirm that all PET-positive sites contained lymphoma; however, the site of biopsy-documented disease demonstrated dramatic clinical and PET improvement after initiation of HAART. In the absence of a standard course of chemotherapy for NHL, her HAART was able to treat an ARL. Another limitation of this case is the short duration of follow-up; therefore, monitoring the patient closely for any signs of recurrence in the future is critical. This clinical situation begs the question—‘‘Can we treat ARL with just HAART?’’ An extensive literature search does not reveal any case report where HAART alone, without chemotherapy, has resolved HIV-associated lymphoma at this stage of the disease. In a post-HAART era, the addition of HAART to standard chemotherapy regimens improves immune response and overall survival. Highly active antiretroviral therapy also significantly reduces chemotherapy-related adverse effects in the treatment of ARL.5 Perhaps, it is time to conduct comparative clinical trials and explore the potential of HAART as a potent sole treatment option for ARL without the harmful effects of existing chemotherapy regimens. Acknowledgments In loving memory of Dr George Perez.

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References 1. Seaberg EC, Wiley D, Martinez-Maza O, et al. Cancer incidence in the multicenter AIDS cohort study before and during the HAART era: 1984 to 2007. Cancer. 2010;116(23):5507-5516. 2. Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123(1):187-194. 3. Biggar RJ, Chaturvedi AK, Goedert JJ, Engels EA. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007;99(12):962-972.

4. Vishnu P, Aboulafia DM. AIDS related Non-Hodgkin’s Lymphoma in the era of highly active antiretroviral therapy. Adv Hematol. 2012;2012:485943. 5. Navarro JT, Lloveras N, Ribera JM, Oriol A, Mate JL, Feliu E. The prognosis of HIV-infected patients with diffuse large B-cell lymphoma treated with chemotherapy and highly active antiretroviral therapy is similar to that of HIV-negative patients receiving chemotherapy. Haematologica. 2005;90(5):704-706. 6. La Ferla L, Pinzone MR, Nunnari G, et al. Kaposi’ s sarcoma in HIV-positive patients: the state of art in the HAART-era. Eur Rev Med Pharmacol Sci. 2013;17(17):2354-2365. 7. Uldrick TS, Whitby D. Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett. 2011;305(2):150-162.

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AIDS-related lymphoma: resolution with antiretroviral therapy alone.

Patients with HIV are at increased risk of malignancy, particularly lymphoma, which is the most common malignancy leading to death. With the advent of...
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