HIV-associated Plasmablastic Lymphoma Research Articles

Abstract PO-033: Unveiling the complexity of HIV-associated plasmablastic lymphoma: A case report of anal cavity presentation with unconventional immunohistochemical profile

Abstract Introduction: HIV-associated Plasmablastic Lymphoma (PBL) stands as a rare subset of Diffuse Large B-cell Lymphoma (DLBCL), marked as an AIDS-defining malignancy. The primary presentation site is the oral cavity. Although extra-oral PBLs have been reported, these are considered to be very rare. Despite its scarcity, understanding its pathogenesis, diagnosis, and management remains paramount. Herein, we elucidate a distinctive case of HIV-associated PBL manifesting in the anal cavity, an infrequent site, accompanied by an intriguing immunohistochemical signature. Clinical Course: A 30-year-old male presented with symptoms indicative of an anal mass, ultimately diagnosed as Plasmablastic Lymphoma. Further evaluation disclosed a pulmonary nodule and a substantial anal-perineum mass. Given the concurrent HIV infection, initiation of retroviral therapy was crucial alongside lymphoma-directed treatment. Notably, immunohistochemical analysis revealed an unusual profile, encompassing positive expression for CD45, CD38, MYC, OCT2, and MUM1, alongside a heightened Ki-67 proliferation index. Conversely, markers such as CD20, PAX5, Pankeratin, CK7, CK20, MART1, CD30, HHV8 CD138 and P63 exhibited negativity. Epstein-Barr virus (EBV) presence was detected. Treatment initiation comprised HyperCVAD chemotherapy, supplemented by intrathecal chemotherapy and methotrexate. Discussion: Immunophenotypically, PBL conventionally lacks CD45, CD20, and CD79a expression while expressing CD38, CD138, and MUM1. However, our case deviated with positive CD45 expression and negative CD138. Treatment paradigms for HIV-associated PBL encompass intensive regimens such as CHOP-alike regimens with other intensive alternatives such as CODOX-M/IVAC, DA-EPOCH or Hyper-CVAD therapy, with limited intrathecal agent utilization to avert central nervous system involvement. Despite aggressive therapeutic measures, prognosis remains guarded. The progression free survival rates range between 6 and 7 months, with median overall survival falling within the 11 to 13 month range. Long-term survivors predominantly emerge among pediatric patients, underscoring potential disparities in disease biology and treatment response. Conclusion: This case epitomizes the heterogeneity and intricacy inherent in HIV-associated Plasmablastic Lymphoma. The unconventional presentation in the anal cavity, coupled with an atypical immunohistochemical profile, poses challenges to diagnostic and therapeutic strategies. Collaborative efforts with specialized centers are imperative for optimal disease management, accentuating the imperative for sustained research endeavors to enhance outcomes in this aggressive lymphoma variant. Citation Format: Aliya M Khan, Mehmet Hepgur, Sophia Navajas. Unveiling the complexity of HIV-associated plasmablastic lymphoma: A case report of anal cavity presentation with unconventional immunohistochemical profile [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-033.

Plasma EBV DNA Methylation: Evidence of EBV Lytic Infection in HIV(+) EBV(+) Plasmablastic Lymphoma

Background: Among people living with HIV, plasmablastic lymphoma (PBL) and classical Hodgkin lymphoma (HL) are almost uniformly associated with Epstein-Barr virus (EBV). Immunohistochemical studies have demonstrated high levels of lytic gene expression in PL,1 whereas EBV(+) HL shows exclusively latent viral gene expression. EBV virion DNA is never CpG methylated, but tumor-derived plasma EBV is CpG methylated as previously shown by our group in EBV(+) HL and nasopharyngeal carcinoma (NPC).2 Others have also presented evidence that patterns of CpG methylation of plasma EBV DNA varies between people with NPC and non-malignant EBV(+) conditions.3 To better characterize the nature of plasma EBV in patients with lymphoma, we investigated EBV DNA copy number and EBV DNA methylation in HIV-associated PBL and HL. Methods: With appropriate approvals from the Human Research Ethics Committee of the University of the Witwatersrand and the Johns Hopkins Institutional Review Boards, we collected plasma from newly diagnosed untreated patients with HIV and PBL or HL in Johannesburg, South Africa. Diagnostic biopsy specimens were reviewed in Baltimore by a hematopathologist to confirm the diagnosis and Epstein-Barr encoding region (EBER) in situ hybridization was performed to determine EBV association. Plasma EBV copies were measured by standard qPCR targeting the BamW repeats. qPCR using the same primers was also performed after capture with methyl-DNA binding protein 2 (MBD2) magnetic beads, where the captured fraction represents methylated DNA and the flow-through represents unmethylated DNA. Results: We studied plasma from 7 patients with PBL and 12 patients with HL. Four of five PBL tumors were EBV (+) and eight of 10 HL tumors were EBV (+) by tissue EBER in situ hybridization. Analysis of plasma EBV DNA copy number showed overlapping levels of EBV DNA (median 2.7 Log10 copy/mL in PBL and 3.2 Log10 copy/mL in HL) (Fig. 1). Patients with at least 1.5 Log10 copy/mL of EBV underwent CpG methylation evaluation, which showed very different EBV CpG methylation indices. The EBV methylation index was highly variable in PBL (median of 51%) and was uniformly high in HL (median of 97%). Conclusions: Although plasma from plasmablastic lymphoma patients show high EBV copy number, the characteristic of that EBV DNA is very different from the plasma EBV detected in Hodgkin lymphoma patients. This difference is hypothesized to be related to evidence of viral lytic gene expression seen in PBL. The degree of plasma EBV DNA methylation may have broad implications for lymphoma diagnosis and subtyping.

HIV-associated plasmablastic lymphoma: A single-centre 12-year experience in Kwa-Zulu Natal, South Africa.

To describe the clinical profile and outcome of patients with HIV-associated plasmablastic lymphoma (PBL) treated with cyclophosphamide, doxorubicin, oncovin, prednisone (CHOP) chemotherapy in a tertiary hospital in KwaZulu-Natal, South Africa. This 12-year retrospective clinical chart review, from 2006 to 2018, of patients with PBL treated with CHOP chemotherapy describes their clinical presentation, complete response (CR), progression-free survival (PFS) and disease-free survival (DFS). Response to salvage chemotherapy was also assessed, as was the overall survival (OS). Of 26 patients included in the study, PBL was the presenting manifestation of underlying HIV infection in 58% (n=15). The median age was 35years (range 13-49), and 62% (n=16) were males. The median CD4 count was 285 cells/µL (range 45-863). All patients had extranodal disease, with 4% having bone marrow involvement (n=1) and >60% presenting with advanced stage and high-risk PBL. Central nervous system (CNS) involvement was present in 15% (n=4). A CR was attained in 46% (n=12). The median DFS was 23.5months (range 5-91months), with an overall 2-year survival of 42% (n=11). Patients with PBL had a low CR with CHOP chemotherapy and poor OS. Use of alternative chemotherapy regimens needs to be investigated to optimally manage this aggressive lymphoma. The surprisingly low incidence of marrow involvement is the focus of ongoing local research.

MYC status in HIV-associated plasmablastic lymphoma: dual-colour CISH, FISH and immunohistochemistry.

We utilised chromogenic and fluorescencein-situhybridisation (CISH and FISH) to evaluate MYCgene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively. Sixty-seven (n=67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYCgene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75days (95% CI 14-136). Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.

Аутологичная трансплантация гемопоэтических стволовых клеток при ВИЧ-ассоциированной плазмобластной лимфоме: клинический случай

Plasmablastic lymphoma (PBL) is a disease that was originally described in 1997 as a distinct subtype of diffuse large B-cell lymphoma (DLBCL), which is more common in patients with HIV infection. It is characterized by extranodal lesions, the most common of which are the oral cavity, digestive tract, and skin3. No generally accepted chemotherapy protocol for the treatment of HIV-associated PBL has been developed. Early consolidation through autologous hematopoietic stem cell transplantation (auto-HSCT) may be a treatment option for advanced patients with concurrent use of highly active antiretroviral therapy (HAART). Disease history. Patient B., 44 years old, with HIV-associated PBL-IV-stage according to AnnArbor with lesions of the alveolar process of the upper jaw, lymph nodes of the neck on the left, bronchopulmonary lymph nodes, and the lower lobe of the right lung, who after 6 courses of chemotherapy according to the standard CHOP regimen, autotransplantation of hematopoietic stem cells was performed in the first remission. Conclusion. Our clinical experience correlates with the few studies on this issue. The patient received stem cell-supported high-dose chemotherapy (HDCT) and his life expectancy is 36 months. Keywords: plasmablastic lymphoma, HIV-associated lymphomas, autologous hematopoietic stem cell transplantation.

HIV-associated plasmablastic lymphoma in the era of HAART: a single-center experience of 21 patients: Erratum.

HIV-associated plasmablastic lymphoma in the era of HAART: a single-center experience of 21 patients: Erratum.

HIV-associated plasmablastic lymphoma in the era of HAART: a single-center experience of 21 patients.

Patients with HIV infection have an increased risk of developing plasmablastic lymphoma (PBL). In this study, we reviewed the clinicopathologic features of PBL in HIV+ patients in the era of HAART from a single health center. Retrospective study. The morphologic, immunophenotypic, and clinical features were reviewed in these HIV+ patients with PBL and univariate analysis was employed to determine the survival prognosis. During the interval of 1 January 2008 to 30 December 2018, we identified 95 HIV+ patients with aggressive non-Hodgkin B-cell lymphomas. Among these patients, there were 21 (22%) patients with PBL (19 men and two women; median age: 45 years). Seven patients had PBL at their initial HIV diagnosis and 14 developed PBL after a median interval of 7.7 months of HIV diagnosis. Lymph nodes (n = 10), oral cavity/sinonasal mass (n = 6), and rectal masses (n = 5) were the common involved sites, and five of 15 (33%) had bone marrow involvement. Lymphoma cells were immunoreactive for MUM-1/IRF4 (100%), CD138 (90%), CD45 (63%), CD79a (47%), and CD30 (25%). Proliferation rate assessed by Ki67 was at least 90% in 18 of 20 cases. Eighteen patients received chemotherapy including etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (n = 13) and cyclophosphamide, doxorubicin, vincristine, and prednisone (n = 2). With a median follow-up time of 19 months, nine out of 17 patients died. Bone marrow involvement was associated with a poorer overall survival (median: 4.7 months, P = 0.015). PBL is the second most common type of aggressive lymphoma and often presents in lymph nodes of patients with poorly controlled HIV infection. Bone marrow involvement is associated with a poorer outcome.

The Genomic Landscape of HIV-Associated Plasmablastic Lymphoma.

A combined whole-exome and targeted sequencing study of 110 cases of human immunodeficiency virus-associated plasmablastic lymphomas revealed a distinct landscape of genetic lesions for this lymphoma entity, including a particular role of mutations in STAT3 and other members of the JAK-STAT signaling pathway, and of the RAS family in its pathogenesis. See related article by Liu et al., p. 112.

Genomic Characterization of HIV-Associated Plasmablastic Lymphoma Identifies Pervasive Mutations in the JAK–STAT Pathway

Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of Human Immunodeficiency Virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK-STAT signaling pathway, including STAT3 (42%), JAK1 (14%) and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches.

Gastrointestinal Tract Plasmablastic Lymphoma in HIV-Infected Adults: A Histopathological Review.

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma that is characterized by the expression of plasma cell antigens and loss of pan B-cell antigens. The neoplasm is extensively reported in the oral cavity and anorectal region but rarely in the gastrointestinal tract, where only isolated case reports and small case series have been reported. In the current study, morphologic, immunohistochemical, and molecular features of 17 cases of gastrointestinal tract PBL were reviewed. Ten-year retrospective study that reappraised the histomorphological and immunophenotypical profiles of HIV-associated PBLs in the gastrointestinal tract. The mean age of the study patients was 41 years with a 3:1 ratio of males to females. The most common site of tumor origin was the small intestine (42%), followed by the stomach (29%) and the colon (29%). Majority of the cases showed a predominant diffuse (82%) growth pattern. Immunoblasts and plasmablasts were observed in all cases. Plasmacytic differentiation was seen in 5 (29%) cases. Additional observations not previously described or emphasized in literature includes pseudo-alveolar growth pattern, centroblast-predominance, multinucleated giant cells, and clear cell change. Immunohistochemistry revealed absence of pan B-cell antigens and expression of plasma cell antigens in all cases. Epstein-Barr virus-encoded RNA was expressed in 53% of the cases. This study highlights the spectrum of histopathological features seen in gastrointestinal tract PBLs. Awareness of this entity and its histopathological features in the gastrointestinal tract is essential for making a timely and accurate diagnosis and improving patient outcomes.

Genomic characterization of HIV-associated plasmablastic lymphoma identifies pervasive mutations in the JAK-STAT pathway.

Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of Human Immunodeficiency Virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK-STAT signaling pathway, including STAT3 (42%), JAK1 (14%) and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches.

185 Acute Kidney Injury in a Patient with HIV-Associated Plasmablastic Lymphoma

185 Acute Kidney Injury in a Patient with HIV-Associated Plasmablastic Lymphoma

Clinical Features of Plasmablastic Lymphoma: Case Series From an Asian Tertiary Cancer Center and Literature Review.

BackgroundPlasmablastic lymphoma (PBL) is an aggressive subtype of mature B-cell non-Hodgkin lymphoma. Given its rarity, there remains a lack of clinicopathological data to guide its management, particularly on Asian patients.MethodsWe conducted a retrospective chart review of 10 patients diagnosed with PBL at the National Cancer Centre Singapore and performed a literature review of similar studies on Asian cohorts.ResultsMost patients were male (n = 9), with median age at diagnosis of 55 years (range, 33 - 91 years). Seven (70%) patients were considered to be immunocompromised. In the overall cohort, the median overall survival (OS) was 19.4 months with 5-year survival estimates given at 60% and 36% for OS and progression-free survival (PFS), respectively. At diagnosis, patients with HIV/AIDS (n = 5) were younger compared to others (median, 43 vs. 61 years; P = 0.0278), had greater number of nodal site involvement (median, 6 vs. 0; P = 0.0333), and higher international prognostic index (IPI) scores (P = 0.034 for trend). Amongst different chemotherapy used, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH)-based regimens (n = 6) elicited prominent complete response rates (83%) and led to durable responses even in the setting of advanced stage, high-risk IPI score and immunodeficiency.ConclusionsIn conclusion, our study describes the features of PBL in an Asian cohort and highlights disease features unique to HIV-associated PBL.

Durable complete remission with combination chemotherapy and bortezomib in HIV-associated plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkin’s lymphoma (NHL) classically seen in patients infected with the human immunodeficiency virus, but can also be seen in other immunocompromised states...

BMET-39CENTRAL NERVOUS SYSTEM INVOLVEMENT BY PLASMABLASTIC LYMPHOMA

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive form of non-Hodgkin's lymphoma with strong HIV association. Management is challenging due to lack of data regarding clinical characteristics, prognostic factors and therapeutic options. Even less is known about central nervous system (CNS) involvement and the role of intrathecal prophylaxis (IT-PX). METHODS: Retrospective review of patients with CNS involvement by PBL treated at Montefiore Medical Center 2002-2013. RESULTS: We identified 16 patients with PBL; 10 (62.5%) were HIV positive. Three (19%) had CNS involvement. Median age was 38 (24-41). At presentation, one had stage IB; two had stage IV disease. CD4 counts were 15, 164 and 434 cells/mm3. Only one of them was on antiretroviral therapy. All three received EPOCH without IT-PX. One patient was lost to follow-up after 3 cycles, but re-presented 33 months later with bulky CNS disease and systemic recurrence. He died 1 month later after treatment with WBRT. The other two developed CNS involvement within 7 months of diagnosis. One received 4 cycles of high-dose methotrexate (HD-MTX) with vincristine and intra-ommaya (IO) cytarabine (Ara-C). However, CSF sampling showed persistent disease and BEAM with autologous stem cell transplant (ASCT) was used as salvage. A second patient had just initiated second line R-ICE when leptomeningeal metastasis occurred. CNS-directed therapy included IO rituximab, MTX, Ara-C and HD-MTX. Her CSF cleared and she received BEAM/ASCT. CNS-directed treatment provided symptom-relief in both cases, but median survival was only 5 months (2-10). Of 11 treated PBL patients, only two (18%) received IT-PX. The remaining five refused chemotherapy or were lost to follow-up. CONCLUSIONS: CNS involvement is not uncommon and may be seen more often in HIV-associated PBLs. CSF-directed treatment can provide symptomatic relief and may produce cytological and radiographic responses. Its utility in preventing CNS seeding and improving survival is less clear.

Current knowledge on HIV-associated Plasmablastic Lymphoma.

HIV-associated PBL is an AIDS-defining cancer, classified by WHO as a distinct entity of aggressive DLBCL. To date less than 250 cases have been published, of them 17 are pediatric. The pathogenesis of this rare disease is related to immunodeficiency, chronic immune stimulation and EBV. Clinically is a rapid growing destructive disease mainly involving the oral cavity even if extraoral and extranodal sites are not infrequent. The diagnosis requires tissue mass or lymph node biopsy and core needle or fine needle biopsy is acceptable only for difficult access sites. Classically immunophenotype is CD45, CD20, CD79a negative and CD38, CD138, MUM1 positive, EBER and KI67 is >80%. Regarding the therapy, standard treatment is, usually, CHOP or CHOP-like regimens while more intensive regimens as CODOX-M/IVAC or DA-EPOCH are possible options. Use of cART is recommended during chemotherapy, keeping in mind the possible overlapping toxicities. Rituximab is not useful for this CD20 negative disease and CNS prophylaxis is mandatory. Intensification with ABMT in CR1 may be considered for fit patients. For refractory/relapsed patients, therapy is, usually, considered palliative, however, in chemo-sensitive disease, intensification + ABMT or new drugs as Bortezomib may be considered. Factors affecting outcome are achieving complete remission, PS, clinical stage, MYC, IPI score. Reported median PFS ranges between 6–7 months and median OS ranges between 11–13 months. Long term survivors are reported but mostly in pediatric patients. Finally, due to the scarcity of data on this subtype of NHL we suggest that the diagnosis and the management of HIV-positive PBL patients should be performed in specialized centers.

Treatment of HIV-associated plasmablastic lymphoma: A single-center experience with 25 patients.

8583 Background: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of B-cell lymphoma with a predominant occurrence in patients with HIV and other immune compromised states. It commonly...

Plasmablastic lymphoma: Does prognosis differ with HIV status and site of disease?

Background: Apart from its common occurrence in the oral cavity in HIV-positive patients, plasmablastic lymphoma (PBL) has also been described at extraoral sites and among immunocompetent individuals. There is sparse data quoting prognostication of PBL depending on the site of occurrence and HIV status of patients. Aims: The present study was carried out at a tertiary oncology center to address the issue whether PBLs occurring at oral and extraoral sites differ prognostically and whether HIV status of patient has any impact on prognosis. Materials and Methods: This was a retrospective observational study conducted at our center on consecutive patients diagnosed with PBL, from January 2008 to December 2012. Results: We had four patients with oral PBL; three male and one female. Sites of involvement were oral tongue and buccal mucosa. Two patients died within 6 months of diagnosis due to disease progression while on treatment. One patient was lost to follow-up after achieving complete remission (CR) after chemotherapy. Only one patient completed the prescribed schedule of chemotherapy and radiotherapy and is in CR with 33 months follow-up. There were four extraoral PBL patients; three female and one male. Extraoral sites were ileocaecal region, ovary, clavicle and rectum. Three patients died within 6 months due to progressive disease during treatment. Only one patient has completed chemotherapy and is in CR with18 months follow-up. Among all these eight oral and extraoral PBL patients, four were HIV positive. Two of them are in CR after treatment (18 months and 33 months follow-up). One patient died during treatment and one patient was lost to follow-up after being in CR. Unfortunately, none of the other four HIV-negative patients could survive for more than 6 months after diagnosis. Conclusion: Both oral and extraoral PBLs have aggressive clinical course and an overall unfavorable outcome. Prognosis of HIV-associated PBL seems to be better with addition of highly active antiretroviral therapy to chemotherapy. Further large sample studies are needed to confirm these results.

Human immunodeficiency virus‐associated plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell lymphoma strongly associated with human immunodeficiency virus (HIV) infection. The authors conducted a multi-institutional, retrospective study to describe characteristics and determine prognostic factors in HIV-associated PBL. For this study, the investigators included consecutive, HIV-positive patients diagnosed between the years 2000 and 2010 whose tumors had a plasmablastic morphology, were cluster of differentiation 20 (CD20)-negative, and expressed markers of plasmacytic differentiation. Fifty patients from 13 institutions were evaluated. The median age was 43 years, and there was a male predominance. The median count of cells that were positive for CD4 (a glycoprotein expressed on the surface of T-helper cells, monocytes, macrophages, and dendritic cells) was 206 cells/mm(3) . At presentation, 90% of patients had extranodal involvement, 69% presented with advanced stage disease, and 27% had oral involvement. Rearrangements of v-myc myelocytomatosis viral oncogene homolog (MYC) were detected in 41% of the tested patients. Eighty-five percent of patients received chemotherapy, with 63% receiving cyclophosphamide, doxorubicin, vincristine, and prednisone and 37% receiving more intensive regimens. The complete response (CR) rate was 66%. The median overall survival (OS) was 11 months regardless of the intensity of chemotherapy. In the survival analysis, an Eastern Cooperative Oncology Group performance status ≥2, advanced stage, and MYC rearrangements were associated significantly with a worse outcome, whereas attaining a CR with chemotherapy was associated with a better outcome. The prognosis of PBL in HIV-infected individuals remains poor in the highly active antiretroviral therapy era. Intensive chemotherapy regimens do not seem to increase survival in patients with HIV-associated PBL. Cancer 2012.

HIV-Associated Plasmablastic Lymphoma: A Multi-Institutional Study

Abstract 1589 Background:Plasmablastic lymphoma (PBL) is a distinct subtype of B-cell lymphoma strongly associated with HIV infection with no more than 150 cases reported in the literature. We conducted a retrospective study to evaluate clinicopathological characteristics and determine prognostic factors in HIV-associated PBL (HIV PBL). Methods:Institutions in the United States (US) and internationally submitted clinical and pathological patient-level data on HIV-positive individuals who had a pathological diagnosis of PBL. According to WHO criteria, all the cases were required to have a plasmablastic morphology, be CD20-negative and to express at least one plasmacytic marker (i.e. CD38, CD138 and/or MUM1/IRF4). Continuous and categorical variables are presented using descriptive statistics. Univariate survival analyses were performed using the Kaplan-Meier method and the log-rank test. Cox proportional-hazard regression test was used for the multivariate survival analysis. P-values of less than 0.05 were considered statistically significant. Results:Thus far, data on 45 patients have been obtained from 11 institutions. Twenty cases (44%) were from Europe, 17 (38%) from the US, 4 (9%) from Africa and 4 (9%) from South America. The median age was 43 years (range: 19–66 years). Of 45 patients studied, 78% (n=35) were men. The median CD4+ count was 177 cells/mm3 (range: 17–683 cells/mm3). The median duration of HIV infection prior to PBL diagnosis was 6 years (range 0–26 years), and 80% (n=36) received HAART. PBL was the initial presentation of HIV infection in 29% (n=13) of the patients. The median viral load at presentation was 45,000 copies/ml (range: undetectable to 4.7 million copies/ml). At presentation, 69% (n=25) of patients exhibited B symptoms, 44% (n=20) had extranodal involvement, 65% (n=28) presented with stage III or IV disease, 20% (n=9) had oral involvement and 39% (n=12) had an absolute lymphocyte count (ALC) <1000 cells/mm3. EBV-encoded RNA was expressed in 94% (n=31), Ki67 >90% was seen in 66% (n=21) and MYC rearrangement was detected in 50% (n=10) of tested patients. Chemotherapy was employed in 89% (n=39) of patients, with 59% (n=23) receiving CHOP. A minority (n=4; 10%) underwent HSCT. Complete response (CR) was obtained in 69% (n=22); however, after 48 months of follow-up, 66% of patients (n=29) have died. The median overall survival (OS) was 11 months (95% CI 7–20 months) from diagnosis. The most common cause of death was PBL progression (n=18; 62%). At the univariate level, adverse prognostic factors for survival included non-CR to chemotherapy (p =0.002), ALC <1000 cells/mm3 (p =0.006), MYC rearrangement (p =0.0005), ECOG performance status >1 (p =0.048), female sex (p =0.02), and advanced stage (p =0.047). At the multivariate level, ALC <1000 cells/mm3 and non-CR were independent adverse prognostic factors in patients with HIV PBL (p =0.01 and p =0.02, respectively). Conclusions:PBL is a rare aggressive B-cell lymphoma, which tends to affect young HIV-positive men who have CD4+ counts <200 cells/mm3. Advanced stage, extranodal involvement, and tumors with EBER expression, MYC rearrangements and Ki67 >90% at presentation are common features of HIV PBL. Although showing a 69% CR to chemotherapy, the median OS remains poor at 11 months. In the multivariate survival analysis, ALC <1000 cells/mm3 and lack of achievement of CR to chemotherapy were independent adverse prognostic factors in HIV PBL. In the HAART era, HIV PBL seems to have a shorter median OS than other HIV-associated aggressive B-cell lymphomas. Disclosures:Montoto:Genentech: Research Funding; Roche: Honoraria. Vose:GSK: Research Funding; Millenium: Research Funding; Celgene: Research Funding; BMS: Research Funding; Exelixis: Research Funding; SBio: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding. Castillo:GlaxoSmithKline: Research Funding; MIllennium Pharmaceuticals: Research Funding.