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

Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy.
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Moulignier A, Lamirel C, Picard H, Lebrette MG, Amiel C, Hamidi M, Polivka M, Mikol J, Cochereau I, Pialoux G,


Moulignier A, Lamirel C, Picard H, Lebrette MG, Amiel C, Hamidi M, Polivka M, Mikol J, Cochereau I, Pialoux G, (click to view)

Moulignier A, Lamirel C, Picard H, Lebrette MG, Amiel C, Hamidi M, Polivka M, Mikol J, Cochereau I, Pialoux G,

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Neurology 2017 07 26() pii 10.1212/WNL.0000000000004265

Abstract
OBJECTIVE
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).

METHODS
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/m(2)) combined with cART.

RESULTS
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.

CONCLUSIONS
Combined short-term HD-MTX monochemotherapy and optimal cART simply and effectively treat AR-PCNSL, achieving long-term survival with few relapses.

CLASSIFICATION OF EVIDENCE
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.

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