Therapy of HIV-associated lymphoma-recommendations of the oncology working group of the German Study Group of Physicians in Private Practice Treating HIV-Infected Patients (DAGNÄ), in cooperation with the German AIDS Society (DAIG).

AIDS-related aggressive B cell lymphoma (HIV-NHL) is the second most common HIV-associated malignancy. In contrast, Hodgkin-lymphoma (HL) is one of the most common non-AIDS-defining malignancies. Current evidence-based recommendations for the treatment of HIV-associated lymphoma (HIV-lymphoma) are not available. A panel of experts in the field of HIV-related lymphoma performed literature searches of the PubMed, Medline, and Cochrane databases. The consensus process was carried out as an e-mail and meeting-based discussion group. Six cycles of R-CHOP or R-EPOCH are standard of care for patients (pts) with diffuse large B cell lymphoma (DLBCL). Pts with Burkitt lymphoma and good performance status should receive dose-intensive regimens such as the GMALL B-ALL/NHL protocol. Standard therapy has not been defined for pts with plasmablastic and primary effusion lymphoma. Pts with lymphoma in sensitive relapse should receive high-dose chemotherapy followed by autologous stem cell transplantation. Stage- and risk adapted treatment yields high remission and survival rates in pts with HIV-HL similar to those achieved in HIV-negative HL pts. Combination antiretroviral therapy (cART) should be applied concurrently to chemotherapy provided that pharmacokinetic interactions are being considered. Pts with HIV-lymphoma should usually be treated in an identical manner to HIV-negative patients.

Stage-adapted treatment of HIV-associated Hodgkin lymphoma: results of a prospective multicenter study.

PURPOSE: Although the outcome of patients with HIV-related Hodgkin lymphoma (HIV-HL) has markedly improved since the introduction of combined antiretroviral therapy, standard therapy is still poorly defined. This prospective study investigates a stage- and risk-adapted treatment strategy in patients with HIV-HL. PATIENTS AND METHODS: Patients with early favorable HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of involved-field (IF) radiation. In patients with early unfavorable HIV-HL, four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP baseline) or four cycles of ABVD + 30 Gy of IF radiation were administered. Six to eight cycles of BEACOPP baseline were given in patients with advanced-stage HIV-HL. In patients with advanced HIV infection, BEACOPP was replaced with ABVD. RESULTS: Of 108 patients (including eight female patients) included in the study, 23 (21%) had early favorable HL, 14 (13%) had early unfavorable HL, and 71 (66%) had advanced-stage HL. The median CD4 count at HL diagnosis was 240/µL. The complete remission rates for patients with early favorable, early unfavorable, and advanced-stage HL were 96%, 100%, and 86%, respectively. The 2-year progression-free survival of the entire study population was 91.7%. Eleven patients (11%) have died, and treatment-related mortality was 5.6%. The 2-year overall survival rate was 90.7% with no significant difference between early favorable (95.7%), early unfavorable (100%), and advanced-stage HL (86.8%). CONCLUSION: In patients with HIV-HL, stage- and risk-adapted treatment is feasible and effective. The prognosis for patients with HIV-HL may approach that of HIV-negative patients with HL.

Whole brain radiation alone produces favourable outcomes for AIDS-related primary central nervous system lymphoma in the HAART era.

Primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS) is a lethal disorder, but the recent application of highly active antiretroviral therapy (HAART) has significantly improved prognosis. This retrospective cohort study of AIDS-related PCNSL examined the actual clinical outcomes and prognostic variables affecting overall survival (OS) in the HAART era. Twenty-three newly diagnosed AIDS-related PCNSL at 12 regional centre hospitals for HIV/AIDS in Japan between 2002 and 2008 were consecutively enrolled. The estimated 3-yr OS rate of the entire cohort was 64% (95%CI, 41.0-80.3%). Whole brain radiation therapy (WBRT) had an independent positive impact on survival (WBRT >or=30 Gy vs. others, P = 0.02). Nine of 10 patients with a good performance status (PS) (0-2) remained alive with complete response, whereas 10 (77%) of 13 of those with a poor PS (3-4) died mostly after a short period. The estimated 3-yr OS rate of the groups with a good and poor PS was 100% and 38% (95%CI, 14-63%), respectively (P = 0.01). Leukoencephalopathy (grade >or= 2) developed in 21% of those that survived more than 12 months after radiation. The patients receiving a curative intent radiation dose (>or=30 Gy) of WBRT achieved prolonged survival while maintaining a good quality of life in the HAART era, especially among patients with a favourable PS.

Lessons from clinical trials in African Burkitt lymphoma.

PURPOSE OF REVIEW: The center of gravity of the AIDS epidemic has moved - in 2007, 67% of all persons living with HIV infection and 72% of all deaths from AIDS occurred in Africa. The present review focuses on the treatment of an AIDS-defining malignancy, Burkitt lymphoma, since the discovery of the tumor in 1958 to provide a backdrop to the increasing necessity of dealing with AIDS-associated Burkitt lymphoma in Africa. RECENT FINDINGS: In Africa, it appears that AIDS-associated Burkitt lymphoma is increasing, but although treatment outcome is presently poor, the demonstration that highly active antiretroviral therapy permits the same treatment results to those in AIDS-unassociated Burkitt lymphoma provides hope for the future. SUMMARY: In the 1960s, the extraordinary response of Burkitt lymphoma to chemotherapy provided considerable encouragement to pioneer oncologists. Within little more than a decade, the most active drugs, the value of combination chemotherapy, and the need for intrathecal treatment, as well as the risk of tumor lysis syndrome had been demonstrated, providing a platform on which further advances could be made in resource-rich countries. Since that time, little progress has been made in Africa, but recent collaborative projects have shown that improved treatment outcome can be achieved at low cost. The impact of the HIV epidemic on the epidemiology and treatment of African Burkitt lymphoma will receive increasing focus in the coming years.

Radiation therapy for HIV-associated diffuse large cell non-Hodgkin lymphoma.

PURPOSE: To report the clinical experience with external beam radiotherapy (RT) for AIDS-related lymphoma (ARL) with or without the involvement of the central nervous system (CNS) in HIV-infected patients. PATIENTS AND METHODS: Clinical outcome of 24 HIV-seropositive patients with ARL treated with RT from 1995 to 2004 was reviewed, testing factors associated with outcome. RESULTS: After 1 and 5 years, the overall survival was 65% and 35%, respectively. The mean RT dose was 31 Gy after normalization to fractions of daily 2 Gy (range, 7.8-47.2 Gy). Radiotherapy dose was associated with survival in univariate (P = .04) and multivariate analysis (P = .01). Other factors in univariate analysis associated with outcome were viral load (VL), highly active antiretroviral therapy (HAART), ARL stage, and CNS involvement. Patients with CNS involvement achieved complete response in 46% and improved clinical performance was seen in 73%. CONCLUSIONS: After chemotherapy, RT in combination with HAART is highly active, and RT should be encouraged especially after suboptimal responses to induction treatment.

Report of AIDS-related lymphoma in South Korea.

BACKGROUND: The prevalence of AIDS-related lymphoma (ARL) is increasing in South Korea. The aim of this study is to identify the clinical features of ARL in South Korea. METHODS: From 1998 through 2006, we retrospectively analysed a total of 23 cases of ARL from seven institutions. RESULTS: The patients consisted of 20 males and 3 females at a median age of 40 (range, 20-72) on diagnosis of AIDS. ARL developed at their median age of 41 (range, 24-72). The histological diagnosis was aggressive B cell lymphoma in the majority, but rare T cell and NK/T cell lymphoma were also included. Ten of 23 (43.5%) was receiving highly active anti-retroviral therapy (HAART) before the diagnosis of ARL. Fifteen of twenty-three patients were given combination chemotherapy with/without radiation, four were given radiation alone, and four did not receive any treatment against medical advice. Of 20 patients followed-up, nine were alive in remission, two alive in disease, one died of treatment related complication, four died of progressive lymphoma, four died of AIDS related causes. The response to treatment included CR in eight (44.4%), PR in four (22.2%) and PD in three (16.7%). The response to HARRT was evaluable in 13 patients based on CD4+ cell count and HIV viral load, among which nine (69.2%) responded. Estimated median survival time was 43.9 months. CONCLUSIONS: Although the population of patients is small, this is the first clinical data analyses of Korean ARL patients. As a substantial portion of the patients remains alive disease free, the impact of HAART on the clinical course of ARL needs further follow-up and evaluation.

Severe HIV-1 encephalitis and development of cerebral non-Hodgkin lymphoma in a patient with persistent strong HIV-1 replication in the brain despite potent HAART -- case report and review of the literature.

A 39 year old patient with HIV-1 infection, who was asymptomatic without antiretroviral therapy (HAART) for ten years, developed severe encephalopathy. Despite therapy with a four drug antiretroviral combination regimen including two protease-inhibitors (PI), plasma viral load could not be suppressed sufficiently with persistence of low level viremia of 3.08-3.40 log copies/ml, even after addition of two other antiretroviral drugs. On therapy the patient showed improvement of clinical symptoms, however with severe persisting cognitive deficits. Repeated parallel measurements of viral load showed a far higher viremia in the cerebrospinal fluid than in the plasma. Resistance testing provided no evidence of relevant PI-mutations and analysis of protease inhibitor levels demonstrated good plasma levels. 17 months after start of HAART, the patient developed a cerebral Non-Hodgkin lymphoma, leading to his death despite radiation therapy. There has been a dramatic reduction in the prevalence of HIV-1 associated CNS events in the post-HAART era. Nevertheless, subgroups of patients are infected with neurotropic viral variants which could cause progressive neurological pathology as they can not be reached sufficiently by the available drugs. These patients require the development of new drugs that achieve a better penetration into the brain.

Sarcoma de Kaposi y linfomas no hodgkinianos asociados con infección por el virus de inmunodeficiencia humana / HIV associated to Kaposi's sarcoma and non-Hodgkin lymphomas

El SIDA es producido por el virus de la inmunodeficiencia humana, tiene la particularidad de infectar y destruir las células del sistema inmune, lo que producen un estado de inmunosupresión irreversible y progresivo en el organismo que se hace susceptible a múltiples infecciones virales, micóticas y bacterianas. Se describen múltiples neoplasias en estos pacientes, pero solo algunos muestran directa relación con el virus de la inmunodeficiencia humana, y su aparición implica el diagnóstico del SIDA: sarcoma de Kaposi, linfomas no hodgkinianos, linfoma cerebral primario y carcinoma de cérvix uterino. El tratamiento de estos pacientes es difícil debido a los problemas provocados por la infección del virus de inmunodeficiencia humana que debilita el sistema inmunitario(AU)

The changing role of radiotherapy in AIDS-related malignancies.

OBJECTIVE: To review the current literature on the role of radiotherapy in AIDS-related malignancies published since 1997. METHODS: A comprehensive literature review was undertaken to review the recent advances in the role of radiotherapy in the management of AIDS-related malignancies. This was combined with the clinical experience from our two London treatment centres for AIDS-related malignancies. A Medline/Pubmed search was performed for articles published since 1997, the year of the previous review, which also coincides with the widespread usage of highly active antiretroviral treatment (HAART). The MESH search terms used were 'HIV or AIDS' and 'radiotherapy'. This search yielded a total of 86 references. CONCLUSIONS: HAART has had a major impact on the role of radiotherapy in AIDS-related malignancy. The use of HAART has led to a decline in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma and has been associated with an improved prognosis in systemic non-Hodgkin's lymphoma in people with HIV. In addition HAART alone has been successfully used as therapy for early KS lesions. Chemoradiotherapy remains the mainstay of management for anal cancer, has a central role in cervical cancer and non-AIDS defining malignancies in this population.

[Multiple medullary and extramedullary plasmacytomas in an HIV infected female patient]. / Plasmocytomes multiples médullaires et extramédullaires chez une patiente infectée par le VIH.

INTRODUCTION: Before the HIV infection era, plasmocyte tumor rarely occurred in patients younger than 40 years of age. Less frequent than lymphomas, the incidence of these blood diseases has however substantially increased in HIV-infected patients. In these patients, in addition to onset at earlier age, their clinical presentation is quite different and extramedullary plasmocytomas in unexpected locations are more common. EXEGESIS: We report the case of a 29-year-old HIV-infected female patient in whom were diagnosed occipital, parotidal, sphenoidal, epidural, and uterine plasmocytomas for which chemotherapy and subsequent radiotherapy were successful. The increase in the incidence of plasmocyte tumors in HIV-infected patients might be facilitated by Epstein Barr Virus (EBV) co-infection, HIV-related chronic antigenic stimulation, and secretion of interleukin 6 by infected lymphocytes. CONCLUSION: Plasmocyte tumors belong to neoplasia whose incidence is increased in HIV infection. Their currently poor diagnosis should be improved by highly active antiretroviral therapies allowing enhanced chemotherapy with possibility of autograft.

Acquired immunodeficiency syndrome-related primary cerebral lymphoma: response to irradiation.

Acquired immunodeficiency syndrome-related primary cerebral lymphoma (AIDS-PCL) is uncommon. Fourteen cases of presumed AIDS-PCL between 1986 and 1995 were reviewed retrospectively in order to characterize the natural history, and the response to radiotherapy. The median age was 38 years (range 24-65). The median interval between seropositive diagnosis of HIV and AIDS-PCL was 28 months (range 5-113). The median duration of symptoms was 2 weeks (range 0.2-12). At presentation, the Eastern Cooperative Oncology Group performance status (PS) was PS1 (2/14 patients), PS2 (6/14) and PS3 (6/14). The symptoms and signs were non-specific and depended on the site and extent of cerebral involvement. There was no characteristic pattern of brain imaging in terms of size, number, location or pattern of contrast enhancement of the cerebral lesions. Nine patients received various fractionation-dose schedules (range 8-50 Gy). Complete and partial responses were seen in 2/9 and 3/9 cases, respectively. Clinical stabilization of neurological symptoms was noted in 3/9 cases and disease progression in 1/9. The median survival times (MST) from presentation for irradiated and non-irradiated patients were 9.3 and 2.1 weeks, respectively (range 0.9-43.1). Although patient selection introduced bias, there appears to be a modest improvement in MST for treated patients. The MST with radiotherapy alone remains poor, but radiotherapy may provide palliation. For some selected patients, a prolonged response is possible.

Anorectal lymphoma and AIDS: an outcome analysis.

BACKGROUND AND OBJECTIVE: Primary lymphoma of the anus is an extremely rare problem. In patients with the Acquired Immune Deficiency Syndrome (AIDS), there is a marked increase in gastrointestinal non-Hodgkin's lymphomas (NHL). The aim of this study was to evaluate the outcome of patients with anorectal NHL and AIDS. METHODS: Over an 18-year period, we identified 6 patients with AIDS and primary anorectal NHL. Five were male. All were high-grade B-cell lymphomas and half showed systemic "B" symptoms. Patient's mean CD4 count was 93 (range 8 to 201). RESULTS: The average life span for those with "B" symptoms was 6.7 months and 16 months for those without symptoms. No benefit was shown from radiation or chemotherapy in those with "B" symptoms. Younger patients and those without systemic constitutional symptoms of lymphoma do better. One patient without "B" symptoms was able to tolerate his radiation and chemotherapy and is disease free at 10 months. CONCLUSION: Despite traditional non-Hodgkin's lymphoma treatment regimens, our AIDS patients (and those examined in a review of the pertinent literature) with anorectal NHL and "B" symptoms have a poor prognosis. For those without "B" symptoms and who can tolerate the therapy, NHL remission may be obtained.