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The biologic complexity of diffuse large B-cell lymphoma (DLBCL) is governed by a dynamic bidirectional relationship between tumor cells and the tumor microenvironment (TME). Prognostic significance of tumour-infiltrating T lymphocytes and T-cell subsets in de novo diffuse large B-cell lymphoma: a multiparameter flow cytometry study. Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma. Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP. [Extracted from the article]

Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors ( p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity ( p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status. [ABSTRACT FROM AUTHOR]

ASPP2 interacts with the tumor suppressor protein p53, promotes damage-induced apoptosis, and can specifically stimulate p53 apoptotic function. Thus, ASPP2 may function as a tumor suppressor and/or play a role in the cellular response to cytotoxic injury. To explore the role of ASPP2 in human cancer, we determined ASPP2 expression in two lymphoma subtypes with differing clinical outcomes: diffuse large B-cell lymphoma (DLBCL) and follicular center lymphoma (FCL). A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to detect ASPP2 mRNA. Sixty-one DLBCL and twenty-three FCL cases were analyzed and normalized ASPP2 levels were expressed relative to an mRNA standard. We found that ASPP2 mean expression strongly correlated with lymphoma subtype: DLBCL = 11.74 and FCL = 4.99 (p = 0.029, unpaired 2-tailed t-test). Importantly, ASPP2 expression was variable in DLBCL but not FCL (DLBCL-range, 0.04-94.6; FCLrange, 1.2-15.0). In these DLBCL cases, serum lactate dehydrogenase (LDH) was an independent predictor of survival with median survival in the high LDH group of 24 months and median survival not achieved in the normal-low LDH group (p = 0.014, Log-Rank Test). Mean ASPP2 levels trended toward an inverse correlation with LDH levels: High LDH, ASPP2 = 6.2; Normal-low LDH, ASPP2 = 18.2 (p = 0.074, unpaired 2-tailed t-test). In the DLBCL cases with ASPP2 levels >7.8, only 10% (1/10) had a high LDH, in contrast to cases with ASPP2 levels < 7.8 in which 59% (26/44) had a high LDH (p = 0.011, Fisher Exact Test). Thus, low ASPP2 mRNA levels may correlate with poor clinical outcome in lymphoma which is consistent with the hypothesis that ASPP2 may play a role in tumor formation and/or sensitivity to cytotoxic agents. Larger studies as well as analysis of different tumor types are warranted. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the heterogeneity and clinical outcome of angioimmunoblastic T-cell lymphoma (AITL). He mentions the study by H-N Lin and colleagues which presents AITL's associated clinicopathologic risk factors and anthracycline-based chemotherapeutic regimens. The author says that the risk factors of AITL invoke geographic and ethnic orientation importance. He hopes that pathogenesis insights from increasing awareness will lead to improved diagnosis for AITL.

We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7 years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0–1 (smIPI, 58.1%), and had non-bulky disease (<7 cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0–1 versus 2–4 was 89.5% versus 69.7%, respectively (P = 0.005). Bulky disease (≥7 cm) was associated with worse PFS and OS on univariable and multivariable analyses (P < 0.05). Patients with smIPI 0–1 without bulky disease have excellent outcomes. However, patients with smIPI 2–4 or bulky disease have a high risk of progression. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (cHL) in young children (ages 0–6) is rare in high income countries (HICs) but is more prevalent in low- and middle-income countries (LMICs) like Guatemala. Given that the majority of cHL studies have evaluated adolescent/adults, and the immune system changes with age, we sought to characterize Epstein-Barr virus (EBV) expression, immune regulatory pathway markers and the tumor microenvironment in 42 children ages 0–6 with cHL from Guatemala. We found a very high frequency of EBV expression (97.5%). Hodgkin cells showed increased expression of PD1 ligands and CD137, indicative of shared immune regulatory mechanisms with adult cHL. Pediatric cHL also showed an increase in CD8+ tumor infiltrating lymphocytes and tumor associated macrophages within the tumor microenvironment. Despite 25 having high risk disease, only 4 patients died from progressive disease, relapse or infection. [ABSTRACT FROM AUTHOR]

As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Forty-six patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90% with 19 (49%) complete response/complete response unconfirmed (CR/CRu) and 16 (41%) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44% at a median follow-up of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia ( n = 8), anemia ( n = 3), thrombocytopenia ( n = 5), congestive heart failure ( n = 4), venous thrombosis ( n = 3), gastrointestinal hemorrhage/perforation ( n = 2), infection ( n = 8) and fatigue ( n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the expression of LMO2 protein, which is a strong predictor of survival in patients with rheumatoid arthritis and diffuse large B-cell lymphoma (DLBCL).

The human germinal center-associated lymphoma (HGAL) gene has prognostic value in diffuse large B-cell lymphoma, and expression of its cognate protein is germinal center-specific. A previous study had suggested that HGAL protein expression might also be related to the outcome in patients with Hodgkin lymphoma (HL). The aim of this study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 patients with classic HL treated uniformly with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Tissue microarray analysis showed HGAL staining in 188 specimens (81%). Failure-free survival (FFS) was superior in patients with early-stage disease, low-risk IPS, and HGAL-positive patients. The estimated 5-year FFS for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (p=0.03). In the multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse FFS. This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical HL. [ABSTRACT FROM AUTHOR]