Characteristics of non-Hodgkin Lymphoma Arising in HIV-infected Patients with Suppressed HIV Replication

Laurence Gérard; Véronique Meignin; Lionel Galicier; Claire Fieschi; Nicolas Leturque; Christophe Piketty; Laurent Fonquernie; Felix Agbalika; Eric Oksenhendler

Disclosures

AIDS. 2009;23(17):2301-2308. 

In This Article

Methods

Design

The present study included patients with plasma HIV-RNA below 500 copies/ml at the time of NHL diagnosis. All these patients have been enrolled in a single-institution, prospective, observational cohort study (HIV lymphoproliferative cohort) recruiting all consecutive HIV-infected patients with a first episode of lymphoproliferative disorder. All patients with NHL included in this cohort study had confirmed HIV infection and histologically or cytologically proven NHL. The diagnosis of PCNSL was made histologically or clinically on the basis of the computed tomography scan characteristics of the lesion and failure to respond to empirical therapy for cerebral toxoplasmosis.

Collection of Data

Standardized data collection forms were completed at NHL diagnosis to provide information about sociodemographic, NHL, and HIV-related characteristics. Lymphomas were pathologically classified according to the WHO classification.[28] Routine staging was performed in all patients, according to the Ann Arbor staging criteria. NHL prognostic score was evaluated by the lymphoma International Prognostic Index (IPI). This index has been found to be prognostic in non-HIV-associated NHL[29] and in HIV-infected patients.[30] The chemotherapy regimens used were categorized into five groups: intensive (ACVBP, COPADM, and CHOP-Methotrexate), standard (CHOP or CHOP-derived), low dose (mini-CHOP and COP), or absence of treatment. Use of rituximab was also recorded. Individuals were classified as cART users if they had used cART for at least 2 months before NHL diagnosis.

A follow-up visit took place within 2 months after the end of chemotherapy. Complete response was defined as disappearance of all evidence of malignant disease. Partial remission and progressive disease were considered as treatment failures. Change in cART during chemotherapy was recorded, and immunovirological status was evaluated. Thereafter, data concerning vital status and NHL relapse were recorded until death or last available visit for patients lost to follow-up.

Pathological and Virological Methods

A centralized review of all available pathological specimens of NHL diagnosis was uniformly analysed by a single pathologist (V.M.), and they were classified according to the WHO classification.[28] Solid primary effusion lymphoma (PEL)-like NHL were classified as PEL.[31,32] The presence of EBV was detected by EBV-encoded RNAs (EBERs) in-situ hybridization and latent membrane protein (LMP) immunohistochemistry, and presence of HHV-8 by latency-associated nuclear antigen (LANA) immunohistochemistry. For patients with only cytological samples available, the detection of EBV and HHV-8 was performed using quantitative real-time PCR. Tumour was defined as virus associated if EBV or HHV-8 was detected in the tumour cells.

Suppression of HIV replication was defined as a plasma HIV-RNA level below the mostly used limit of detection since 1996 (500 copies/ml). The duration of HIV suppression was calculated from the first undetectable plasma HIV-RNA sample, without any plasma HIV-RNA measurement above 500 copies/ml, until NHL diagnosis.

Statistical Methods

Individuals were followed prospectively from enrolment in the cohort until death, last follow-up visit, or 1 September 2008, whichever occurred first. Descriptive analysis used medians with interquartile range (IQR) values. Comparison between groups used Wilcoxon rank-sum test for continuous variables, and Pearson chi-squared or Fisher's exact test for noncontinuous variables. All P values were two-sided. Survival was estimated using the Kaplan–Meier method and was tested using the log-rank test. All analyses were conducted using Stata, version 9.2 (StatCorp Inc., College Station, Texas, USA).

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