Plasmablastic Lymphoma: A Series of 16 Cases with the Largest Collection of 9 HIV-Negative Cases

Plasmablastic lymphoma (PBL) is a distinctive B-cell lymphoma that shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts and having an immunophenotype of plasma cells. It was originally described as a rare variant of diffuse large B cell lymphoma involving the oral cavity and occurring in the clinical setting of HIV and latent EBV infection (Delecluse et al. 1997). However, the natural history of this disease in HIV-negative (HIV-) patients is poorly understood due to its rarity.

Patients with a histologic diagnosis of PBL from January 1999 to June 2010 at Moffitt Cancer Center were identified and their charts were reviewed. Relevant clinical, pathologic, laboratory data and treatment variables were recorded and analyzed.

A total of 16 patients with PBL were evaluated including 9 HIV- cases, 5 HIV positive (HIV+) cases and 2 cases with unknown HIV status. The mean age at diagnosis was 39.8 and 58.4 years for HIV+ and HIV- patients (p=0.01) respectively. Flow cytometry and/or immunohistochemical staining analyses showed all cases phenotypically expressed at least one plasma cell marker (CD138 12/14; bright CD38 8/8; MUM1 8/8) and were negative for B-cell markers tested (CD20 16/16; PAX-5 3/3).

All 5 HIV+ patients had CD4 count less than 100 (range 5–82). All 4 patients that had documented EBV status were positive. They all presented with advanced stages ranging from IIIB to IVB. Two patients received treatment, but did not have any response. All the HIV+ patients died within 6 months from diagnosis.

HIV- cases (9) were more heterogeneous (summarized in Table 1). The stage at diagnosis varied from IE to IV. The list of common disease sites in the order of the frequency was following: oral-facial structures (5), lymph nodes (LN) (4), bone marrow (BM) (2), bone (1), GI tract (1). EBV was associated with 4 out of 7 cases while in 2 patients, the EBV status was unknown. Patient #5 developed PBL secondary to EBV reactivation 5 months post umbilical cord blood allogeneic stem cell transplant (HSCT) for MDS. Seven out of 9 patients received CHOP as a front-line therapy and 2 were treated with hyper-CVAD. Six out of 8 patients with assessed responses achieved complete response (CR), while one had very good partial response adequate for HSCT consolidation and the other one required salvage therapy. Four patients underwent autologous HSCT after achieving CR1. Three of them were stage IV at diagnosis and 1 was stage IIB. Two of these 4 patients were alive and disease-free (A-NED) at the end of the follow-up. The remaining 2 patients (#2 and #3) had disease recurrence at 2 and 14 months post HSCT, respectively. Interestingly, the patient #3 was treated with bortezomib/dexamethasone and achieved CR2. Despite consolidation with allogeneic HSCT, this patient recurred in 5 months post HSCT and died. The mean overall survival for our HIV- patients was 46.6 months with median survival not reached.

Our study suggests that HIV- PBL is a heterogeneous disorder in terms of etiology and clinical course. A limited understanding of pathobiology and a lack of active biological agents for this subtype of B-cell lymphoma due to absence of cell surface CD20 expression might result in unfavorable prognosis in patients with advanced stages. Currently, more aggressive induction chemotherapy and consolidation with HSCT in CR1 have been offered to this group of patients at our center. A role of bortezomib in the front-line or relapse treatment settings needs to be tested on a larger cohort of patients.

Off Label Use: Bortezomib use in this type of disease is considered off-label. Similarly, rituximab use is also off-label since CD20 is negative in this disease.