A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Anti-apoptotic MCL1 Protein Represents Critical Survival Molecule for Most Burkitt Lymphomas and BCL2-negative Diffuse Large B-cell Lymphomas.

The pro-survival MCL1 protein is overexpressed in many cancers, including B-cell non-Hodgkin lymphomas (B-NHL). S63845 is a highly specific inhibitor of MCL1. We analyzed mechanisms of sensitivity/resistance to S63845 in preclinical models of diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Annexin V-based cytotoxic assays, Western blot analysis, protein co-immunoprecipitation, and cell clones with manipulated expression of BCL2 family proteins were used to analyze mechanisms of sensitivity to S63845. Experimental in vivo therapy with S63845 and/or venetoclax was performed using patient-derived xenografts (PDX) of treatment-refractory B-NHL. A subset of DLBCL and majority of Burkitt lymphoma cell lines were sensitive to S63845. The level of BCL2 protein expression was the major determinant of resistance to S63845: BCL2 serves as a buffer for pro-apoptotic proteins released from MCL1 upon exposure to S63845. While BCL2-negative lymphomas were effectively eliminated by single-agent S63845, its combination with venetoclax was synthetically lethal in BCL2-positive PDX models. Concerning MCL1, both, the level of MCL1 protein expression, and its occupational status represent key factors mediating sensitivity to S63845. In contrast to MCL1-BIM/BAK1 complexes that prime lymphoma cells for S63845-mediated apoptosis, MCL1-NOXA complexes are associated with S63845 resistance. In conclusion, MCL1 represents a critical survival molecule for most Burkitt lymphomas and a subset of BCL2-negative DLBCLs. The level of BCL2 and MCL1 expression and occupational status of MCL1 belong to the key modulators of sensitivity/resistance to S63845. Co-treatment with venetoclax can overcome BCL2-mediated resistance to S63845, and enhance efficacy of MCL1 inhibitors in BCL2-positive aggressive B-NHL.

Novel Biological Insights and New Developments in Management of Burkitt Lymphoma and High-Grade B-Cell Lymphoma.

OPINION STATEMENT: Burkitt lymphoma (BL) is highly curable, and prompt institution of therapy is critical to achieving optimal outcomes. Although current "standard" approaches are very effective in disease eradication, treatment-related toxicity makes optimal delivery of curative therapy a challenge, especially in older and immunocompromised individuals. Reduced intensity approaches with fewer toxic complications have been the focus of some recent studies. A critical question is if they can replace "standard" approaches by maintaining high curability with improved tolerability. Additionally, new molecular insights in BL biology suggest that in the future, "targeted therapy" approaches may be feasible using small molecule inhibitors and novel strategies. Recently, a new category of aggressive lymphoma named "high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 translocations" has been recognized. This category overlaps clinically and biologically with BL and has an inferior prognosis compared to most B-cell lymphomas, and the optimal approach to its management remains, as yet, undefined. In this review, we discuss the current landscape of BL treatment including recent results with low-intensity regimens and also consider current approaches to HGBL. We also explore how recently elucidated novel biological insights in BL biology may shape future therapeutic directions including the use of novel cellular therapy approaches.

Chemotherapy Treatments for Burkitt Lymphoma: Systematic Review of Interventional Studies.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive hematologic cancer. This study synthetized the evidence about the efficacy and safety of chemotherapy treatments used in patients with BL using the World Health Organization classification. MATERIALS AND METHODS: A systematic review of interventional studies was performed. A search was carried out in PubMed, Scopus, and Web of Science, with additional manual and gray literature searches. The methodological quality of articles was assessed with the Newcastle-Ottawa scale. RESULTS: We identified 1358 studies; 9 nonrandomized studies satisfied the eligibility criteria (n = 544 patients). The BL epidemiologic variants were sporadic BL (44.5%), endemic BL (47.2%), and immunodeficiency-associated BL (8.3%). Regarding chemotherapy protocols, 4 groups were identified: based on CODOX-M/IVAC (n = 4), EPOCH (n = 1), BFM (n = 1), and simplified treatment schemes used in African countries (n = 3). Most studies had moderate quality. Empirically and qualitatively, the best options for adults with sporadic BL were 'DA-EPOCH-R' (7-year overall survival [OS], 100%; 95% confidence interval [CI], 82-100), 'HDR + LD into CODOX-M/IVAC' (2-year OS, 84%), and 'RD-CODOX-M/IVAC' (4-year progression-free survival, 92%; 95% CI, 77-100); in pediatric patients, the 'BFM-NHL-90-like' showed promising results (3-year OS, 90%). For immunodeficiency-associated BL, the 'SC-EPOCH-RR' demonstrated a good therapeutic profile (6-year OS, 90%; 95% CI, 60-98). The 'Malawi 2012-2014' (1-year OS, 73%; 95% CI, 61-85) could be the treatment choice in endemic BL (African countries). The main adverse events were hematologic. CONCLUSION: Selecting chemotherapy protocols for BL should be grounded in its epidemiologic variants. Further studies with greater methodological quality are needed to strengthen the evidence.

Real-world outcomes of AIDS-related Burkitt lymphoma: a retrospective study of 78 cases over a 10-year period.

We investigated the clinical characteristics and outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma (AIDS-BL). A single-center retrospective study was performed of 78 cases over a 10-year period. The baseline characteristics of enrolled patients included the following: median age, 46 years; median CD4+ T lymphocyte count, 156 cells/µL; advanced stage, 74.3%; > 1 extranodal site, 55.1%; international prognostic index (IPI) > 1, 85.9%; and elevated serum lactate dehydrogenase, 82.1%. The 1-year and 2-year overall survival (OS) rates were 52.2 ± 5.9% and 42.7 ± 6.2%, respectively. A prognostic analysis of 65 patients who had undergone chemotherapy showed that B symptoms (with vs. without fever, night sweat or weight loss), number of extranodal sites (0, 1 vs. > 1), level of serum albumin (≥ 35 g/L vs. < 35 g/L), hemoglobin (≥ 110 g/L vs. < 110 g/L), and IPI score (≤ 2 vs. > 1) were all associated with OS. However, only B symptoms (HR = 4.036, 95% CI 1.821-8.948, p = 0.001), serum albumin level < 35 g/L (HR = 2.131, 95% CI 1.013-4.483, p = 0.046), and chemotherapy without rituximab (HR = 2.286, 95% CI 1.108-4.714, p = 0.025) were independent predictors of OS after multivariate adjustment. Patients with AIDS-BL were likely to present with high-risk features, and their clinical outcomes were relatively poor, especially those with B symptoms and lower serum albumin levels.

Prognostic Stratification of Patients with Burkitt Lymphoma Using Serum ß2-microglobulin Levels.

PURPOSE: We aimed to investigate the prognostic value of serum ß2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system. MATERIALS AND METHODS: A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum ß2-microglobulin levels. A risk-stratifying classification system incorporating serum ß2-microglobulin levels was proposed and validated in an independent validation cohort (n=60). RESULTS: The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum ß2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.01 for both). Serum ß2-microglobulin levels further stratified patients in the low-risk and high-risk groups in terms of PFS (p=0.010 and p=0.044, respectively) and OS (p=0.014 and p=0.026, respectively). Multivariate analyses revealed that a high serum ß2-microglobulin level (> 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum ß2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes. CONCLUSION: Serum ß2-microglobulin level is an independent prognostic factor for BL patients. The proposed ß2-microglobulin-based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.

SPAG6 promotes cell proliferation and inhibits apoptosis through the PTEN/PI3K/AKT pathway in Burkitt lymphoma.

The main purpose of the present study was to elucidate the role of sperm­associated antigen 6 (SPAG6) in the occurrence and development of Burkitt lymphoma (BL) and explore the underlying molecular mechanisms. A correlation was observed between the expression of SPAG6 and the prognosis of patients with lymphoma using The Cancer Genome Atlas (TCGA) database analysis. It was demonstrated that the levels of SPAG6 in BL cells were higher compared with that in IM­9 cells by reverse transcription­PCR and western blot assays. Moreover, silencing of SPAG6 significantly decreased proliferation and increased apoptosis of Daudi and Raji cells, whereas SPAG6 overexpression exerted the opposite effects on CA46 and NAMALWA cells. When investigating the possible mechanism, it was first observed that the level of phosphatase and tensin homolog (PTEN) protein was significantly increased, while that of phosphorylated (p­)AKT protein was markedly reduced in the SPAG6­knockdown group compared with the blank control group in Daudi and Raji cells by western blot analysis. It was further ascertained whether the phosphoinositide 3­kinase (PI3K)/PTEN/protein kinase B (AKT) pathway mediates the effects of SPAG6 on cell proliferation and apoptosis, and the results demonstrated that silencing of SPAG6 suppressed the viability of Daudi and Raji cells, whereas PTEN knockdown using siRNA or SF1670 (a specific PTEN inhibitor) reversed the inhibitory effect on cell proliferation and the promoting effect on cell apoptosis induced by SPAG6 depletion in vitro as well as in vivo. These data revealed that SPAG6 may promote the proliferation and inhibit the apoptosis of BL cells via the PTEN/PI3K/AKT pathway. The results of the present study suggest that SPAG6 may play a key role in the progression of BL and may be of value as a predictive prognostic biomarker in patients with BL.

MYC functions as a switch for natural killer cell-mediated immune surveillance of lymphoid malignancies.

The MYC oncogene drives T- and B- lymphoid malignancies, including Burkitt's lymphoma (BL) and Acute Lymphoblastic Leukemia (ALL). Here, we demonstrate a systemic reduction in natural killer (NK) cell numbers in SRα-tTA/Tet-O-MYCON mice bearing MYC-driven T-lymphomas. Residual mNK cells in spleens of MYCON T-lymphoma-bearing mice exhibit perturbations in the terminal NK effector differentiation pathway. Lymphoma-intrinsic MYC arrests NK maturation by transcriptionally repressing STAT1/2 and secretion of Type I Interferons (IFNs). Treating T-lymphoma-bearing mice with Type I IFN improves survival by rescuing NK cell maturation. Adoptive transfer of mature NK cells is sufficient to delay both T-lymphoma growth and recurrence post MYC inactivation. In MYC-driven BL patients, low expression of both STAT1 and STAT2 correlates significantly with the absence of activated NK cells and predicts unfavorable clinical outcomes. Our studies thus provide a rationale for developing NK cell-based therapies to effectively treat MYC-driven lymphomas in the future.

BI6727, a polo-like kinase 1 inhibitor with promising efficacy on Burkitt lymphoma cells.

OBJECTIVE: BI6727, an ATP-competitive PLK1 inhibitor, has been shown to cause cell death in multi-tumors. This study aimed to investigate the anti-tumor effect and potential molecular mechanism of BI6727 in human Burkitt lymphoma (BL) cell lines. METHODS: We assessed polo-like kinase 1 (PLK1) expression in BL patient tissues and cells, also investigated the cytotoxic effect using CCK8 assay and flow cytometry. In addition, western blotting and real-time polymerase chain reaction (RT-PCR) assays were used to explore the molecular mechanisms of BI6727 in human BL cell lines. RESULTS: PLK1 was overexpressed in BL cells compared with normal cells. The PLK1 inhibitor BI6727 reduced activated PLK1 expression and caused mitotic arrest in BL cells. Additionally, BI6727 suppressed cellular proliferation and induced apoptosis in BL cell lines. BI6727 treatment also decreased C-MYC protein and mRNA expression, blocked the PI3K/AKT/mTOR signaling pathway, and stabilized the FBXW7 protein. CONCLUSIONS: Our findings explained a potential molecular mechanism of BI6727 in BL cells and suggested that BI6727 might be a new therapeutic agent for BL in the future.

Outcome at the end of treatment of patients with common and curable childhood cancer types in Blantyre, Malawi.

BACKGROUND: The WHO Global Initiative for Childhood Cancer aims to increase survival to at least 60% for all children with cancer globally, with initial focus on six common curable cancer types. Frequent causes of treatment failure in low income countries (LICs) are treatment abandonment and death during treatment. Here, we report on the outcome at the end of treatment of patients with newly diagnosed common and curable cancer types, admitted in the Queen Elizabeth Central Hospital, Blantyre, Malawi. PROCEDURE: Outcome at end of treatment was documented and analyzed retrospectively for all children with a working diagnosis of a common and curable cancer type (ALL, Hodgkin disease, Wilms tumor, retinoblastoma, and Burkitt lymphoma) admitted over a 2-year period. Patients with a misdiagnosis were excluded. Outcomes were categorized as alive without evidence of disease, treatment abandonment, death during treatment, or persistent disease. RESULTS: We included 264 patients. Seven patients with a misdiagnosis were excluded. At the end of treatment, 53% (139 of 264) of patients were alive without evidence of disease, 19% (49 of 264) had abandoned treatment, 23% (61 of 264) had died during treatment, and 6% (15 of 264) had persistent disease. CONCLUSION: Survival of children with common and curable cancers is (significantly) below 50%. Almost half (42%) of the patients either abandoned treatment or died during treatment. Strategies to enable parents to complete treatment of their child and improved supportive care are needed. Such interventions may need to be given priority to improve the currently poor survival.

Rituximab is highly effective in children and adolescents with Burkitt lymphoma in Risk Groups R2 to R4.

Data regarding the use of rituximab in children and adolescents with Burkitt's lymphoma (BL) is limited. This study retrospectively analyzed the effect of rituximab on children and adolescents with BL in risk group (R) 2 to R4. Patients underwent chemotherapy according to the revised NHL-BFM-95 protocol. Rituximab was administered at the dose of 375 mg/m2 on day 0 of each cycle. A total of 106 patients were included. Stratified by the number of doses of rituximab, there were 49, 16, and 41 patients in group 1 (no rituximab), group 2 (1-3 doses of rituximab) and group 3 (≥4 doses of rituximab), respectively. The 3-year event-free survival (EFS) rates were 83.2% (95% CI = 72.6%-93.8%), 81.2% (95% CI = 52.3%-93.5%) and 96.8% (95% CI = 78.8%-99.6%) in group 1, group 2 and group 3, respectively (p = 0.077). In R2/R3, the relapse rates were 0 in patients treated with rituximab and 11.8% in those treated without rituximab (p = 0.516). In R4, the relapse rates were 18.8%, 21.4% and 3.0% in group 1, group 2 and group 3, respectively (p = 0.048). Rituximab is highly effective in children and adolescents with BL in R2 to R4. The optimal number of doses was 4-6 in patients with BL in R4.

Clinicopathological analysis of oral Burkitt's lymphoma in pediatric patients: A systematic review.

The aim of this study was to integrate the available data regarding pediatric Burkitt's lymphoma (BL) of the oral cavity. A systematic review was conducted following PRISMA guidelines, through a specific search strategy. Twenty-nine publications were included in this study, resulting in a total of 144 cases. Oral BL was predominantly found in males (75.7%). The mandible was the most involved site (37.5%), and all cases clinically exhibited a swelling. Presence of EBV was observed in 33.3% of the cases, and 4 cases reported HIV-positive patients (33.3%). Chemotherapy was the leading treatment choice for oral BL (94.9%), and the overall 5-year survival was 54.3%. Regarding the quality assessment of the studies, most (19 studies; 65.5%) were classified as an overall moderate risk of bias. In conclusion, the clinicopathological characteristics of oral BL in the pediatric population comprise the sporadic and intermediate subtypes. Despite its aggressiveness, this malignancy presents a moderate overall survival.

Clinicopathologic Characterization of Children With B-Cell Non-Hodgkin Lymphoma Over 10 Years at a Tertiary Center in Cape Town, South Africa.

BACKGROUND: We characterized B-cell non-Hodgkin lymphoma (NHL) cases over 10 years at a tertiary children's hospital to contribute to the body of knowledge on pediatric lymphoma in developing countries with a high human immunodeficiency virus (HIV) burden. METHODS: A retrospective cohort study was carried out using clinical and laboratory records of children newly diagnosed with B-cell NHL from January 2005 to December 2014. RESULTS: Seventy-five children ≤15 years of age were included. The majority had Burkitt lymphoma (n=61). Overall, (n=19) were HIV positive and 16% (n=12) had concurrent active tuberculosis. Bulky disease was present in 65.7% (n=46) and 30.1% (n=22) were classified as Lymphomes Malins B risk group C. The 5-year survival estimates for HIV-negative and HIV-positive children were similar in our cohort: 81% versus 79% for event-free survival and 85% versus 83.9% for overall survival. Of 3 children with Burkitt lymphoma, HIV, and Lymphomes Malins B group C, 2 died within 1 year. CONCLUSIONS: Irrespective of HIV status, the survival of children in our B-cell NHL cohort compares favorably with cure rates in developed nations, although advanced disease remains associated with a poor prognosis. Characterization of childhood NHL cases contributes to accurate risk stratification and tailored treatment.

Experience with provisional WHO-entities large B-cell lymphoma with IRF4-rearrangement and Burkitt-like lymphoma with 11q aberration in paediatric patients of the NHL-BFM group.

Large B-cell lymphoma with IRF4 rearrangement, and Burkitt-like lymphoma with 11q aberration are two provisional lymphoma entities in the 2017 revision of the WHO classification of lymphoid neoplasms. Despite being more frequent in young patients, knowledge regarding their true incidence and clinical features in unselected cohorts of paediatric and adolescent patients is limited. We screened for both entities among paediatric patients (<18 years of age) in the German NHL-BFM (Non-Hodgkin lymphoma Berlin-Frankfurt-Münster) group. Among follicular lymphomas and diffuse large B-cell lymphomas (DLBCL), 7/34 cases (21%) showed an IRF4 break-apart pattern by fluorescence in situ hybridisation (FISH) and are associated with stages I and II disease (P = 0·043). Among lymphomas morphologically resembling Burkitt lymphoma, DLBCL and high-grade B-cell lymphoma, unclassifiable, 13/102 cases (13%) lacked a MYC break-apart pattern but were positive for 11q proximal gain and telomeric loss by FISH. MYC-negative Burkitt-like lymphomas with the typical 11q gain-loss pattern by FISH were older (P = 0·004), showed less male predominance (P = 0·003), lower stage (P = 0·040), lower serum LDH level (P = 0·01) and less abdominal involvement (P = 0·008) compared to high grade B-cell lymphomas without 11q gain-loss pattern. Both entities showed excellent outcome with overall survival of 100% when managed according to NHL-BFM strategies and may provide candidates for future therapy de-escalation in clinical trials.

A long-term retrospective study on sporadic Burkitt lymphoma in chinese population.

Burkitt lymphoma (BL), an aggressive malignancy, brings a prognosis varying among children, adolescents, and adults. Most of previous retrospective studies of BL focused on a part of population. This study aimed to find the leading prognostic factors in BL among patients of different age groups. World Health Organization classification of lymphoid neoplasms in 2008 and revision in 2016 were used as diagnostic criteria for BL. We compared the laboratory results and clinical manifestations in 2 age groups by Kaplan-Meier survival analysis. Our study strongly indicated that age >14 years and lactate dehydrogenase >570 U/L were 2 powerful prognostic factors for BL. The results indicated that poor prognosis may be for the poor tolerance and low dose of drugs in adolescents and adults.

Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy: an international study of 264 real-world patients.

Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: -0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.

Clinicopathological features of primary thyroid Burkitt's lymphoma: a systematic review and meta-analysis.

BACKGROUND: Primary thyroid Burkitt's lymphoma (BL) is an extremely rare and highly aggressive form of non-Hodgkin's lymphoma; only isolated case reports are available for patients with this disease. METHODS: We analyzed the clinicopathological features of thyroid BL by conducting a meta-analysis of 21 known patients (including ours) and compared them to those of extrathyroidal BL. RESULTS: There were 13 men and 8 women with a median age of 39.3 years (range, 6-75 years). The median follow-up was 46.5 months (range, 0.5-361 months). Six patients (28.6%) had stage I disease, 2 (9.5%) had stage II, 2 (9.5%) had stage III, and 11 (52.4%) had stage IV. Five of 7 tested patients with thyroid BL (71.4%) had histological evidence of underlying Hashimoto's thyroiditis. Ki-67 labeling indices exceeding 90% in all 19 patients tested (100%). Fluorescence in situ hybridization performed on 12 patient samples revealed that all (100%) had MYC rearrangement. Among the 16 patients for whom follow-up data were available, 4 died of disease-related causes. Kaplan-Meier analysis revealed that the 12- and 60-month overall survival rates for patients with thyroid BL were 87.5 and 70.7%, respectively. CONCLUSIONS: Ours was the largest study of thyroid BL and its detailed clinicopathological features to date. Thyroid BL is not associated with underlying Epstein-Barr virus infection but is closely linked to Hashimoto's thyroiditis; patients generally have good overall survival and respond well to intensive chemotherapy. The correct pathological diagnosis is essential for treatment selection and outcome improvement.

CD30 expression and survival in posttransplant lymphoproliferative disorders.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of transplantation. For refractory and relapsed PTLD new therapies are needed, such as the antibody-drug conjugate brentuximab vedotin that targets CD30. There is limited knowledge of CD30 expression in various subtypes of PTLD and its correlation to clinicopathological features. Therefore, we studied the expression of CD30 in PTLD following solid organ transplantation and correlated CD30 expression to PTLD subtype, Epstein-Barr virus (EBV)-status, intratumoral regulatory T-cells (Tregs), clinical features, and outcome.Methods: We included 50 cases of PTLD from a nation-wide study of PTLDs following solid organ transplantation in Sweden. The tumor biopsies were reevaluated, and clinical data were collected. CD30 expression on tumor cells was analyzed by immunohistochemistry with the clone Ber-H2. Thirty-one cases were stained with clone 236 A/E7 for detection of forkhead box protein 3 (FoxP3, a Treg biomarker).Results: The case series consisted of 6% polymorphic, 88% monomorphic, and 6% Hodgkin lymphoma-like PTLDs and 53% of the cases were EBV+. Overall, 70% (35/50) of the PTLDs were CD30+ (≥1% CD30+ tumor cells) and 30% (15/50) were CD30-. All polymorphic PTLDs (n = 3) and Hodgkin lymphomas (n = 3), 88% (14/16) of non-germinal center type of diffuse large B-cell lymphoma (DLBCL), and 75% (9/12) of T-cell PTLDs were CD30+ whereas all germinal center-type of DLBCL (n = 5) and Burkitt type PTLD (n = 2) were CD30-. CD30+ PTLD tended to be EBV+ more frequently (p = .07) and occurred earlier posttransplant (2.1 vs. 8.2 years, p = .01) than CD30- PTLD. Type of transplant and localization of the tumor did not differ between the groups except that CNS engagement was more common in CD30- PTLD (p = .02). CD30-status was not associated with presence of intratumoral Tregs or overall survival.Conclusion: Expression of CD30 varied with PTLD subtype. There was no association between CD30 and survival, regardless of subtype.

In the South African setting, HIV-associated Burkitt lymphoma is associated with frequent leukaemic presentation, complex cytogenetic karyotypes, and adverse clinical outcomes.

South Africa (SA) has a high prevalence of human immunodeficiency virus (HIV) infection. People living with HIV are at markedly increased risk of developing Burkitt lymphoma (BL), which is characterized by the MYC translocation. There is a paucity of survival data of HIV-associated Burkitt lymphoma/leukaemia (HIV-BL) cases from SA, and the relationship between karyotype and outcomes has not been widely reported. Here we report the clinico-pathological characteristics of a cohort of cytogenetically confirmed HIV-BL cases. A retrospective, descriptive review was conducted of clinico-pathological features of HIV-BL patients newly diagnosed and treated between 2005 and 2014 at our tertiary academic institution in Cape Town. Only HIV-BL patients with cytogenetic evidence of a MYC translocation were included for analysis. A multivariable Cox proportional hazards model assessed the impact of variables on overall survival (OS). Forty-nine patients met inclusion criteria. Their median age was 37 years (IQR 30-43 years) and 57% (n = 28) were females. Their median CD4 count was 240 cells/µl (IQR 103-423 cells/µl). The majority, 61% (n = 30), had leukaemic presentation, and 20% (n = 10) had a complex karyotype on conventional karyotyping. Seventy-seven percent (n = 36) received various protocols of combination intensive chemotherapy, excluding rituximab. Their OS was 64% (95% CI 45-77%) at 6 months, and 34% (95% CI 17-51%) at 5 years. Leukaemic presentation and a complex karyotype gave a 2.7-fold (95% CI 1.0-6.7) and 2.6-fold (95% CI 1.1-6.6) increased risk of mortality respectively, which were statistical significant (p < 0.05). We report 49 newly diagnosed, cytogenetically confirmed HIV-BL patients at our institution over a 10-year period. There was a high proportion of complex karyotypes and leukaemic presentation, which both independently adversely affected survival. This may be due to differences in the pathobiology of HIV-BL that requires further study and could lead to therapeutic advances in this patient group.