Acquired Immunodeficiency Syndrome (AIDS)-Associated Lymphomas
Diagnosis
Clinicians should perform imaging studies to evaluate for nonpalpable, pathologic adenopathy when patients present with unexplained constitutional symptoms that last for more than 2 weeks, such as weight loss, fevers, and night sweats. (I)
Clinicians should obtain biopsies of lymph nodes that are newly developed, pathologically enlarged (typically >2 cm), or progressively enlarging. (I)
Clinicians should have diagnoses confirmed by experts at a referral center or commercial laboratory whenever possible. (III)
Concurrent Highly Active Antiretroviral Therapy (HAART) and Lymphoma Therapy
Patients currently receiving HAART should continue their antiretroviral (ARV) regimen while undergoing therapy unless there are other indications for an interruption of ARV treatment. (III) If ARV therapy is interrupted in patients receiving ARV medications with prolonged half-lives, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs), clinicians should consult with an human immunodeficiency virus (HIV) Specialist for guidance on how to avoid the emergence of resistance.
If possible, clinicians should avoid using zidovudine in patients receiving chemotherapy. (III)
Clinicians should individualize prophylaxis for opportunistic infections in patients receiving chemotherapy. (I) When patients present with CD4 counts in the normal range (400-1400 cells/mm3), prophylaxis should be dictated by the severity of immunosuppression anticipated from the chemotherapy regimen.
Key Point:
Although chemotherapeutic drugs may have overlapping toxicities with ARV drugs, it is common practice to continue HAART during chemotherapy. However, because experience with newer ARV medications and cancer chemotherapy is limited, the clinicians should maintain vigilance for unusual or unusually severe toxicities.
Specific Lymphoma Histologies
B-Cell Diffuse Large Cell Lymphoma (B-DLCL)
Treatment
Whenever possible, HIV-infected patients should be treated with the same full-dose chemotherapy regimens that would be used in the absence of HIV infection. (III)
Clinicians should refer patients to research centers for protocol participation whenever feasible. (III)
Relapsed and Primary Refractory Disease
Clinicians should consider experimental high-dose therapy and stem cell support for patients with relapsed or refractory disease who have good performance status and well-controlled HIV disease. (III) Treatment for other patients remains palliative.
Primary Effusion Lymphoma
Key Point:
Specific recommendations for treatment cannot be made on the basis of clinical trial, although therapy directed at B-DLCL is reasonable.
Primary B-Cell CNS Lymphoma
Treatment for primary B-cell central nervous system (CNS) lymphoma is primarily palliative radiation and dexamethasone, (III) although a small, highly selected group of patients may benefit from chemotherapy.
Burkitt's and Burkitt's-like Lymphoma
There is no uniformly accepted treatment for this highly aggressive form of lymphoma. Clinicians should consider the use of regimens applicable to the non-HIV-infected population, particularly if the CD4 count is high and the associated HIV comorbidities are few. (III)
Plasmablastic Lymphoma
There are no known successful treatments for plasmablastic lymphoma.
Hodgkin's Disease
Both ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) and the more recently described Stanford V regimen are reasonable treatments for HIV-associated Hodgkin's disease. (I)
Clinicians should consider patients with relapsed or primary refractory Hodgkin's disease and well-controlled HIV for research protocols of intensive therapy with peripheral blood stem cell support. (III)
Indolent Lymphoma
Treatment should be commensurate with the lymphoma diagnosis (I) unless precluded by HIV comorbidities (III).
(See Appendix A in the original guideline document for treatment options for HIV-associated lymphomas.)
Kaposi's Sarcoma (KS)
Diagnosis
When the clinician suspects KS based on visual inspection, biopsy of at least one lesion should be obtained to confirm the diagnosis and to differentiate KS from other pigmented lesions. (III)
Cutaneous KS
As part of the annual skin examination, the clinician should examine the oral cavity and the entire skin surface, including the soles of the feet, scalp, external genitalia, and ears, for the presence of abnormal pigmented lesions. (I)
Nodal KS
Key Point:
Unless lymph nodes are sufficiently enlarged or asymmetric to warrant biopsy for exclusion of lymphoma, there is no need to routinely biopsy enlarged lymph nodes in patients with biopsy-proven KS elsewhere.
Gastrointestinal KS
In the absence of gastrointestinal symptoms, radiographic or endoscopic evaluation of the gastrointestinal tract is not recommended for routine staging of KS (III). However, when a patient with known cutaneous KS presents with unexplained gastrointestinal symptoms (particularly pain, bleeding, or signs of obstruction), the clinician should perform an endoscopic evaluation of the upper and/or lower gastrointestinal tract (I).
Pulmonary KS
When a patient with known cutaneous KS presents with dyspnea, wheezing, and/or hemoptysis, clinicians should perform a differential diagnosis for pulmonary KS by obtaining x-rays, scans, and/or bronchoscopy to exclude infections and other neoplastic processes (e.g., lymphoma, lung cancer). (I)
Treatment
Unless immediate chemotherapy is indicated, the clinician should first attempt to optimize HIV control in patients receiving no or suboptimal ARV therapy because KS may respond to this alone (I). Patients should also receive prophylaxis for and treatment of opportunistic infections (I) (for more information on infectious diseases associated with HIV infection, see the National Guideline Clearinghouse [NGC] summaries of the New York State Department of Health [NYSDOH] guidelines Mycobacterial infections and Infectious complications associated with HIV infection: parasitic infection).
Clinicians should use chemotherapy consisting of either a liposomal anthracycline (liposomal doxorubicin or liposomal daunorubicin) or paclitaxel as first-line therapy for patients with the following KS manifestations (I):
- Documented pulmonary KS
- Symptomatic visceral KS
- Extensive, symptomatic KS-associated lymphedema
- Extensive and symptomatic or rapidly progressive cutaneous KS
For patients who do not require immediate chemotherapy for life-threatening or highly symptomatic KS, clinicians should use one of the following approaches (I):
- Local topical, injectable, or radiation therapy of cutaneous lesions
- Low-dose interferon alfa
- Participation in clinical trials of novel therapeutic agents targeting the pathogenic mechanisms involved in KS
Key Point:
Advanced HIV infection itself is not a contraindication to chemotherapy for treatment of KS.
(See Appendix A in the original guideline document for treatment options for HIV-associated KS.)
Cervical Dysplasia and Cancer
Cervical Dysplasia
Screening for Cervical Dysplasia
Clinicians should perform a gynecologic examination in HIV-infected women during the baseline evaluation. Pap tests should be performed, regardless of the woman's sexual orientation. It should be performed during the initial physical examination, repeated at 6 months, and then repeated annually, as long as the results are normal (see Table 2 in the original guideline document).
Women with abnormal Pap tests should be referred for colposcopy and further evaluation that may include human papilloma virus deoxyribonucleic acid (HPV DNA) testing, cervical biopsy, cervical curettage, and endometrial biopsy, depending on cell type and the degree of the cytological abnormality.
Cervical Cancer
Management of Cervical cancer
Clinicians should refer HIV-infected women to a gynecologic oncologist or surgeon trained in management of cervical cancer when possible. Appropriate staging, management, and therapy for cervical cancer should be determined by a gynecologic oncologist or clinician with similar training and experience.
(See Appendix A in the original guideline document for treatment options for HIV-associated cervical cancer.)
Anal Dysplasia and Cancer
Screening and Diagnosis
At baseline and as part of the annual physical examination for all HIV-infected adults, regardless of age, clinicians should:
- Inquire about anal symptoms, such as itching, bleeding, diarrhea, or pain
- Perform a visual inspection of the perianal region
- Perform a digital rectal examination (III)
Clinicians should refer women with cervical high-grade squamous intraepithelial lesion (HSIL) and any patient with abnormal anal physical findings, such as warts, hypopigmented or hyperpigmented plaques/lesions, lesions that bleed, or any other lesions of uncertain etiology, for high-resolution anoscopy and/or examination with biopsy of abnormal tissue.
Clinicians should obtain anal cytology at baseline and annually in the following HIV-infected populations (Frisch et al., 2001; Frisch, Biggar, & Goedert, 2000; Anderson et al., 2005; Goncalves et al., 2005; Caselli et al., 2005; Gaggin, Lauchin, & Steben, 2005; Diaz-Arrastia & Harrington, 2005; Head, 2005; Berry, 2005; Konstantinopoulos, Schlecht, & Bryan, 2006; Peters, Mack, & Bernstein, 1984; Melbye & Sprogel, 1991; Frisch, Olsen, & Melbye, 1994; Rabkin et al., 1992; Abramovitz et al., 2007):
- Men who have sex with men
- Any patient with a history of anogenital condylomas
- Women with abnormal cervical and/or vulvar histology
Key Point:
If the digital rectal examination is performed in conjunction with anal cytology and/or high-resolution anoscopy (HRA), the cytology must be obtained first, before lubrication is introduced into the anal canal.
Anal Cytology Screening
Clinicians should refer patients with abnormal anal cytology for high-resolution anoscopy and possible biopsy.
Treatment of Anal High-Grade Squamous Intraepithelial Lesions
Patients should receive post-treatment serial monitoring with annual HRA.
Treatment of Anal Cancer
Primary care clinicians should refer HIV-infected patients with anal cancer to an oncologist for treatment.
For patients with untreated invasive anal cancer without evidence of distant metastases and CD4 counts >200 cells/mm3, combined modality therapy with concurrent radiation and combination chemotherapy should generally be administered. In situ carcinoma is not treated with radiotherapy or chemotherapy.
(See Appendix A in the original guideline document for treatment options for HIV-associated anal cancer.)
Non-AIDS-Defining Cancers
Clinicians should promote risk-reduction behaviors, such as smoking cessation, and should adhere to standard, age-appropriate screening recommendations, such as mammography and colonoscopy, that apply to the non-HIV-infected population. (I)
Although there are no specific guidelines for the treatment of incident, non-AIDS-defining cancers in HIV-infected patients and treatment needs to be individualized, clinicians should not a priori treat such patients with less aggressive therapy than would be used in similarly staged patients without HIV infection. (III)
Key Point:
Clinicians should be vigilant for the development of cancers that are not specifically associated with HIV infection but that are common in the general population, such as lung cancer, breast cancer, colorectal cancer, prostate cancer.
Definitions:
Quality of Evidence for Recommendation
- Evidence from one or more properly randomized, controlled trial
- Evidence from one or more well-designed clinical trial without randomization; from cohort or case-controlled studies
- Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
