Long-term survival in AIDS-related primary central nervous system lymphoma

Abstract

Background. The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention. Methods. To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX). Results. We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre-versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART. Conclusion. Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.

Optimizing treatment of HIV-associated lymphoma

“…34,35 Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH), an infusional regimen given over 5 days, emerged as Table 1. OS of HIV lymphoma subtypes both pre-and post-ART Pre-ART, % Current ART era, % Burkitt lymphoma 10-40 36,57,58,119 70-80 61,62 DLBCL 40 119 70-80 36,37 HL 55 87 80-90 86,87 PBL 6 64 75 68 Primary CNS lymphoma 20 69 60 73,74 the predominant approach after a 2003 US National Cancer Institute (NCI) study showed a 79% complete remission (CR) rate. 36 Building on EPOCH, AMC trial AMC-034 favored the addition of concurrent over sequential rituximab, the anti-CD20 antibody 37 ; the study found a 12% rate of febrile neutropenia, a 28% rate of any grade 3 or 4 infection, and 2-year rates of progression-free survival (PFS) and overall survival (OS) in the range of 70%.…”

“…71 A pilot study using only zidovudine (1.5 g twice daily), ganciclovir (5 mg/kg twice daily), and IL-2 (2 000 000 U twice daily) had 2 of 5 patients remaining in CR at 28 months and 52 months, but closed early because of low patient accrual. 72 Induction regimens are generally based on high-dose methotrexate, and retrospective studies of AIDSrelated primary CNS lymphoma include 14 ART-era patients whose 5-year OS was 60%, 73 and 51 ART-era patients whose 5year OS was 48%. 74 Several novel approaches are available for HIV 2 primary CNS NHL, but there are no data on their effectiveness in the setting of HIV.…”

Biology of CNS lymphoma and the potential of novel agents

“…Epstein-Barr virus (EBV) is detected in virtually all cases of AIDS-related PCNSL, distinct from PCNSL arising in the immunocompetent, in which 5% to 15% of cases are EBV positive. 7 …”

Is ultrasound combined with computed tomography useful for distinguishing between primary thyroid lymphoma and Hashimoto’s thyroiditis?

“…In our study, all patients had a history of HT. Lymphoma was a malignant tumour originating from the lymphatic haematopoietic system leading to the enlargement of cervical lymph nodes [41].…”