Sporadic Burkitt’s lymphoma/acute B-cell leukaemia presenting with progressive proptosis and orbital mass in a child

Abstract Lymphocyte function-associated antigens 1 and 3 (LFA-1, LFA-3) and intercellular adhesion molecule 1 (ICAM-1) are cell surface adhesion molecules necessary for immune processes requiring intercellular contact. It was recently proposed that malignant Burkitt's lymphoma cells (BL) may escape from immunosurveillance through the downregulation of LFA-1 (CD11a/CD18) or LFA-3 (CD58) and ICAM-1 (CD54) molecules. Expression of these three adhesion antigens was investigated in 19 BL lines. LFA-1 or LFA-3 expression was found to be absent or low in 8 of 11 Epstein-Barr virus (EBV) genome positive BL, but strongly expressed on all nonmalignant EBV genome positive lymphoblastoid cell lines (LCL). Negative or weak expression of LFA-1 and LFA-3 was also observed in 7 of 8 EBV genome negative BL. ICAM-1 was found to be expressed on the cell surface of the majority of BL lines. BL lines growing as individual cells did not express LFA-1, whereas clump- forming BL lines expressed this marker involved in B-cell homotypic aggregation. Expression of LFA-1 and LFA-3 was induced on in vitro infection of EBV-negative BL cells with the immortalizing EBV strain B95–8, and weakly with the nonimmortalizing EBV strain P3HR1. EBNA2 and LMP, two EBV encoded proteins expressed in LCL and in BL infected with B95–8 (BL/B95–8), are not expressed in P3HR1 infected BL cells (BL/P3HR1). Stable expression of EBNA2 after gene transfer in a BL/P3HR1 cell line did not restore the level of LFA-1 and LFA-3 found on BL/B95–8 cells. In EBV-positive BL cells expressing LFA-1 and LFA-3, LMP was found coexpressed, supporting the recent finding of the role of LMP in B-cell adhesion receptor activation. Consequently, diminished LFA-1 and LFA-3 expression appears to be a common characteristic of numerous EBV-positive BL as well as EBV-negative BL. These findings are discussed in the framework of BL pathogenesis.

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Burkitt’s Lymphoma and B-Cell Lymphoma Unclassifiable With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt’s Lymphoma in Patients With HIV: Outcomes in a South African Public Hospital

Journal of Global Oncology ◽

10.1200/jgo.2015.002378 ◽

2017 ◽

Vol 3 (3) ◽

pp. 218-226 ◽

Cited By ~ 5

Author(s):

Gerhard Sissolak ◽

Matthew Seftel ◽

Thomas S. Uldrick ◽

Tonya M. Esterhuizen ◽

Nooroudien Mohamed ◽

...

Keyword(s):

South Africa ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma ◽

High Dose ◽

Baseline Serum ◽

Large B Cell Lymphoma ◽

Large B Cell

Purpose Burkitt’s lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. Methods We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa. Differences between BL and BL/DLBCL, survival outcomes, and factors associated with survival were analyzed. Results There were 35 patients with either HIV-associated BL (24) or BL/DLBCL (11) who met study criteria. Median CD4+ T-lymphocyte count at lymphoma diagnosis was 188 cells/μL (range, 10 to 535 cells/μL). Patients with BL/DLBCL were significantly older and had less bone marrow involvement and lower baseline serum lactase dehydrogenase than patients with BL. Eighty-nine percent of patients presented with advanced disease, and 25% had baseline CNS involvement. Chemotherapy regimens consisted of cytoreduction with low-dose cyclophosphamide, vincristine, and prednisone followed by induction with vincristine, methotrexate, cyclophosphamide, doxorubicin and prednisone (LMB 86; 57%); hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (hyper-CVAD; 20%); cyclophosphamide, doxorubicin, vincristine, and prednisone and high-dose methotrexate with leucovorin rescue on day 10 with accompanying prophylactic IT chemotherapy (Stanford regimen; 14%); and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-like; 9%) regimens. Twenty-three patients received CNS treatment or prophylaxis, and 31 received concurrent combination antiretroviral therapy. Two-year overall survival was 38% (95% CI, 22% to 54%) and 2-year event-free survival was 23% (95% CI, 11% to 38%), with no difference between histologic subtypes. Common causes of death were infection (41%) and CNS disease progression or systemic relapse (41%). Conclusion Cure of HIV-associated BL and BL/DLBCL with intensive regimens is possible in resource-limited settings, but lower toxicity regimens, improved CNS prophylaxis, and increased resources for supportive care are required.

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