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report five patients with human immunodeficiency virus-1/acquired
immunodeficiency syndrome (HIV-1/AIDS) who developed T-cell large
granular lymphocytic proliferation (T-LGLP) or leukemia (T-LGLL). None
of the patients fulfilled criteria for diagnosis of diffuse
infiltrative lymphocyte syndrome (DILS) or HIV-associated CD8+
lymphocytosis syndrome at the time of diagnosis of LGL. The
immunophenotype of malignant T-cells was identical in three patients
with co-expression of CD3, CD8, CD57, and T-cell receptor (TCR)
alpha/beta. Three out of five patients were also diagnosed with clonal
disorders of B-cell origin including diffuse large B-cell lymphoma,
Burkitt’s lymphoma, and monoclonal gammopathy of undetermined
significance (MGUS). Two patients developed cytopenias due to
T-LGLL prompting initiation of therapy. Our study suggests that chronic
viral infection with HIV can contribute to the evolution of T-LGLP.
Clinical and laboratory characteristics of T-LGLP associated with
HIV-1/AIDS resemble those of immunocompetent patients.
Case 3A 47-year-old Caucasian male was diagnosed with HIV in 2000. He was treated with emtricitabine, tenofovir, lopinavir, and ritonavir, but became non-compliant with therapy from 2006 until 2008.
Case 4A 51-year-old Caucasian man presented with unintentional weight loss, diarrhea, and acute renal failure in January 2009. His CBC revealed absolute lymphocytosis >10 x109/L. Flow cytometry on peripheral blood was consistent with a CD8+ lymphoproliferative disorder. Esophagogastroduodenoscopy and colonoscopy with biopsies revealed non-specific inflammatory changes from the distal esophagus through the colon. Immunohistochemistry showed a colonic infiltration with an atypical lymphoid population co-expressing CD2, CD3, CD5, CD8 and TCR alpha/beta.
Case 5A 58-year-old male presented with unintentional weight loss, night sweats, and fatigue in 2009. He was found to have extensive abdominal and retroperitoneal lymphadenopathy and was diagnosed with stage 3B Burkitt’s lymphoma and HIV. At the time of diagnosis, his CD4 count was 0.050x109/L, and viral load was 69,000 copies/mL. He was started on cyclophosphamide, vincristine, doxorubicin, dexamethasone, cytarabine, and methotrexate (hyperCVAD) as well as emtricitabine, tenofovir, lopinavir, and ritonavir. He achieved complete remission, and his viral load became undetectable. Lopinavir was switched to efavirenz due to side effects. His viral load remained undetectable with CD4 counts > 1.0x109/L.
DiscussionA hallmark of HIV infection is a depletion of infected helper CD4+ cells resulting in an increased incidence of opportunistic infections and AIDS-defining malignancies. The introduction of HAART therapy results in a significantly decreased incidence of such malignancies, as well as an improved patient outcome.[9,10] HIV-associated mature T-cell malignancies comprised only 3% of all AIDS-related lymphomas in a single institutional study in the US. However, significantly higher frequency (27%) was observed in a study from South America, suggesting geographical and ethnic differences.
ConclusionsWe describe five unique patients with HIV/AIDS who developed persistent expansions of clonal T-cell LGLs while their HIV infection was controlled with HAART (Table 1). All patients fulfilled earlier or more recent criteria for the diagnosis of LGLL (Table 2).
|Table 1. Characterization of HIV/AIDS Method of highly active antiretroviral therapy (HAART) utilized is recorded, where available. Response to HAART is characterized by CD4 count and HIV viral load. (N/A = not available).|
|Table 2. All five patients met criteria for T-cell LGL leukemia or large granular lymphocytic proliferation. (ANC-absolute neutrophil count, ALC-absolute lymphocyte count, LGL-large granular lymphocyte, TCR-T cell receptor gene, BMBx-bone marrow biopsy, CSA: cyclosporine A, G-CSF-granulocyte-colony stimulating factor, obs-observation.).|