AIDS-related Primary CNS Lymphoma Research Articles

The Imaging Features of AIDS-Related Primary CNS Lymphoma; Case Series and Literature Review

The Imaging Features of AIDS-Related Primary CNS Lymphoma; Case Series and Literature Review

Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy

To assess the characteristics and outcomes of patients with AIDS-related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy (cART) era systematically treated with high-dose methotrexate (HD-MTX). We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and treated with a median of 6 (range 1-15) infusions of HD-MTX (3 g/m2) combined with cART. Median all-patients' and survivors' follow-up lasted 23 (range 0-186) and 76 (range 23-186) months, respectively. At PCNSL diagnosis, 83% of the patients were on cART, median plasma HIV load was 175,600 copies/mL, and median CD4+ T-cell count was 24/μL. Median Eastern Cooperative Oncology Group performance status was 2 (range 1-4). Median overall survival (OS) was 5.7 years, with 5- and 10-year rates of 48% and 41%. Median time to progression was not reached (69% at 10 months). PCNSL was the direct cause of 14 deaths, all observed within the 10 months after its diagnosis: 6 patients died before HD-MTX could be administered, 4 had refractory disease, and 4 relapsed. Multivariate analyses retained time interval between AIDS diagnosis and PCNSL diagnosis, age at AR-PCNSL diagnosis, and deep brain structure involvement as independent OS-predictive factors. To restore effective immune function, cART tailored to HIV genotypes was started and combined with HD-MTX; no interactions and no immune reconstitution inflammatory syndrome occurred. No patient died of acute treatment-related toxicity, and 21 of 51 (41%) patients experienced grade 3/4 toxicity. Combined short-term HD-MTX monochemotherapy and optimal cART simply and effectively treat AR-PCNSL, achieving long-term survival with few relapses. This study provides Class IV evidence that short-term HD-MTX monochemotherapy improves long-term survival of patients with AIDS with primary CNS lymphoma receiving cARTs.

AIDS-related primary CNS lymphoma

AIDS-related primary CNS lymphoma

The management of primary central nervous system lymphoma related to AIDS in the HAART era

The review highlights the recent advances in the pathogenesis, diagnosis and treatment of AIDS-related primary CNS lymphoma (AIDS-PCNSL). The incidence of AIDS-PCNSL has decreased in the era of highly active antiretroviral therapy (HAART). The prognosis has improved and this most probably in relation both with the HAART-induced immunologic status recovery and subsequently the possibility to use more aggressive treatment strategies. Immunomodulatory effect of HAART seems also to have an indirect antitumor activity on the disease. The treatment strategy for AIDS-PCNSL in the HAART era tends to become similar to that of the immunocompetent population. In the absence of randomized trials devoted to AIDS-PCNSL, most current national comprehensive cancer network guidelines recommend the use of high-dose methotrexate-based chemotherapy combined or not with whole-brain radiotherapy as initial treatment in addition to HAART. The objective for the future would be that prognosis of AIDS-PCNSL catch up with that of the immunocompetent patients with special attention to systemic and neurocognitive tolerance of the treatments.

B lymphocytes in the normal brain: contrasts with HIV-associated lymphoid infiltrates and lymphomas.

In recent years evidence has accumulated which suggests that the brain may not be the immunologically privileged site it was once considered to be. It is now widely accepted that T lymphocytes perform surveillance functions in normal brain parenchyma. However, as yet there are no reports of B lymphocytes entering brain parenchyma in the healthy state. This study aimed to determine first the prevalence of B lymphocytes in normal brain, and subsequently whether advancing HIV infection led to changes in the brain B lymphocyte population, which might contribute to the increased risk of lymphoma seen in AIDS. Our results show that B lymphocytes do enter all parts of the normal human brain in very low numbers and that the B lymphocytes within the brain parenchyma display an activated (CD23 positive) phenotype. In contrast, intravascular B lymphocytes have a much lower expression of activation markers. B lymphocytes were found in increased numbers in both the brain parenchyma and perivascular spaces of pre-AIDS brains. However, brains from the majority of AIDS subjects, including those with primary CNS lymphoma (PCNSL) (outside the area of neoplastic involvement) contained fewer B lymphocytes than normal or pre-symptomatic HIV-infected brains. A subset of AIDS brains, previously shown to have pleomorphic lymphoid infiltrates in the perivascular spaces, had significantly increased numbers of B lymphocytes in both the brain parenchyma and perivascular spaces. Virtually all AIDS-related PCNSL are known to be Epstein-Barr Virus (EBV) positive, in contrast to non-HIV PCNSL and non-CNS AIDS-related lymphomas. We examined the EBV status of brain parenchymal B lymphocytes to investigate whether EBV-positive B lymphocytes are more frequent in HIV-infected brains than normal, thus explaining the propensity for CNS lymphomas in AIDS. In situ hybridization studies showed EBV positivity only in AIDS-related PCNSL cases within the lymphoma deposits. PCR-based studies detected high EBV copy numbers in PCNSL tumour tissue, and low copy numbers in AIDS cases with pleomorphic lymphoid infiltrates. As none of the B lymphocytes in this latter group were EBV positive on in situ hybridization, bearing in mind that this appears to be a prerequisite for PCNSL development, we find no evidence that pleomorphic infiltrates represent a pre-malignant PCNSL state.

Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.

EBV AND AIDS-RELATED PRIMARY CNS LYMPHOMA

EBV AND AIDS-RELATED PRIMARY CNS LYMPHOMA

Epstein-Barr virus in AIDS-related primary central nervous system lymphoma

Primary central nervous system lymphoma occurs more often in patients with AIDS. Epstein-Barr virus (EBV) has been detected in these tumours, but the degree of association has not been defined because of both the highly restricted expression of EBV in malignant tissue and the lack of a technique that is reliable in formalin-fixed paraffin-embedded specimens. EBV-transformed lymphocytes contain short non-protein coding EBV transcripts (EBERs), which are expressed in much higher quantity than other EBV-latency transcripts. We describe a new strategy for detection of latent EBV with these transcripts as targets for in-situ hybridisation. 18 cases of Al DS-related primary CNS lymphoma from a consecutive necropsy series together with specimens from 3 further cases were studied. In each case, a strong positive signal over tumour cells indicated abundant expression of the EBV-EBER1 transcript. This 100% association suggests that the pathogenesis of these AIDS-associated lymphomas may differ from the systemic disease in which only 30-50% of tumours are associated with EBV. A pathogenetic role for EBV was further supported by showing expression of a viral protein (the latent membrane protein) that is implicated as an effector for EBV-associated lymphomagenesis. EBV might have a role as a tumour marker in the diagnosis and management of AIDS-related primary CNS lymphoma.

CT Appearance of Primary CNS Lymphoma in Patients with Acquired Immunodeficiency Syndrome

Cranial CT studies of 32 patients with biopsy-proven AIDS-related primary CNS lymphoma were reviewed retrospectively. A wide variety of different CT appearances were identified. Mass lesions varied in location, size, and number. Most lesions were either iso- or hyperdense and all enhanced with contrast medium. Several different patterns of enhancement were observed. Mass effect and edema were seen in almost all patients. After radiotherapy, most tumors decreased in diameter, became hypodense, and no longer enhanced with contrast medium. Edema and mass effect decreased or resolved in all but one patient. Postradiotherapy CT scans also revealed interval enlargement of the ventricles and cortical sulci. This study demonstrates the wide diversity of CT appearances of AIDS-related primary CNS lymphoma. The CT findings cannot be used in lieu of biopsy for diagnosis of this disorder. The appearance of postradiotherapy CT scans was consistent with regressing lymphoma.