Interleukin-7 treatment of PML in a patient with idiopathic lymphocytopenia.

OBJECTIVE: To describe the compassionate use of interleukin-7 (IL-7) for treatment of progressive multifocal leukoencephalopathy (PML) in the setting of idiopathic CD8+ greater than CD4+ lymphocytopenia. METHODS: A 66-year-old HIV-seronegative man presented with progressive language dysfunction. MRI showed hyperintense lesions in the left hemispheric white matter with mild contrast enhancement. A brain biopsy performed 4 months after symptom onset established the diagnosis of PML. The patient had profound lymphocytopenia with absolute lymphocyte count (ALC) at 168 cells/µL, 87 CD4+ T cells/µL, and 7 CD8+ T cells/µL. There was no evidence of hematologic malignancy or rheumatologic disease. RESULTS: The patient received 3 intramuscular injections of IL-7 at a dose of 10 µg/kg per week with no adverse effects. ALC peaked at 595 cells/µL, CD4+ T cells at 301 cells/µL, and CD8+ T cells at 34 cells/µL 3 weeks after completion of treatment. His lesions on MRI stabilized and neurologic examination mildly improved. JCV-specific T-cell responses measured by intracellular cytokine staining were not altered after treatment with IL-7 but there was a marked increase in regulatory T cells. CONCLUSION: This case further supports the investigational use of IL-7 in patients who develop PML in the setting of ICL. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with ICL and PML, IL-7 improves PML-related-outcomes. The study is rated Class IV because it is a case report.

Brief Report: Role of Thymic Reconstitution in the Outcome of AIDS-Related PML.

Implications of thymopoiesis in AIDS-related opportunistic infections remain unexplored. We used progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), as an opportunistic infection model, and we simultaneously investigated thymic output and T-cell responses against JCV in 22 patients with PML treated with combined antiretroviral therapy. Thymic output was significantly associated with JCV-specific CD4⁺ and CD8⁺ T-cell responses and improved survival. Our data suggest that patients with AIDS-related PML and impaired thymopoiesis are less likely to develop a robust JCV-specific cellular immune response and consequently are at an increased risk for a poor clinical outcome.