Prognostic Impact of Serum ß2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients.

The significance of serum beta-2 microglobulin (sß2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sß2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8-3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sß2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sß2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff ("normal versus high"). In multivariate analysis, sß2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sß2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sß2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sß2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a "normal versus high" cutoff set at 2.4 mg/L.

Incorporating Monoclonal Antibodies into the First-Line Treatment of Classical Hodgkin Lymphoma.

The long-term survival of Hodgkin lymphoma (HL) patients treated according to the current standard of care is excellent. Combined-modality schedules (ABVD plus radiotherapy) in early-stage disease, along with treatment intensity adaptation to early metabolic response assessed by PET/CT in advanced stage HL, have been the cornerstones of risk stratification and treatment decision-making, minimizing treatment-related complications while keeping efficacy. Nevertheless, a non-negligible number of patients are primary refractory or relapse after front-line treatment. Novel immunotherapeutic agents, namely Brentuximab Vedotin (BV) and immune checkpoint inhibitors (CPI), have already shown outstanding efficacy in a relapsed/refractory setting in recent landmark studies. Several phase 2 single-arm studies suggest that the addition of these agents in the frontline setting could further improve long-term disease control permitting one to reduce the exposure to cytotoxic drugs. However, a longer follow-up is needed. At the time of this writing, the only randomized phase 3 trial so far published is the ECHELON-1, which compares 1 to 1 BV-AVD (Bleomycin is replaced by BV) with standard ABVD in untreated advanced-stage III and IV HL. The ECHELON-1 trial has proven that BV-AVD is safe and more effective both in terms of long-term disease control and overall survival. Just recently, the results of the S1826 SWOG trial demonstrated that the combination nivolumab-AVD (N-AVD) is better than BV-AVD, while preliminary results of other randomized ongoing phase 3 trials incorporating anti-PD-1 in this setting will be soon available. The aim of this review is to present the recent data regarding these novel agents in first-line treatment of HL and to highlight current and future trends which will hopefully reshape the overall management of this disease.

Are We Identifying Malnutrition in Hospitalized Patients with Hematologic Malignancies? Results from a Quality Clinical Audit.

Disease-related malnutrition (DRM) is highly prevalent among patients with hematologic malignancies. The aim of the present study was to evaluate the prevalence of DRM in hospitalized patients with hematologic malignancies and investigate the level of awareness of DRM among the medical team treating this group of patients. A cross sectional quality clinical audit took place in two hematology units of a tertiary university hospital. Inpatients were screened within 48 h of their admission using the Malnutrition Universal Screening Tool (MUST) to identify their nutritional risk, and they were reassessed to identify the implemented interventions during their hospitalization. One hundred eighty-five patients were included in the audit analysis. On admission, 37.3% of the audited population was identified as being at high risk of malnutrition according to the MUST score. Forty-nine (26.5%) patients reported reduced food intake during the past 5 days, while four (2.2%) reported no food intake. During the hospitalization, only five patients (2.7%) received nutritional support, as indicated. Low levels of awareness of the early detection and treatment of DMS were found. Moreover, the prevalence of DRM and low nutritional intake was reported to be low. Measures to increase awareness of DMR in the medical team and better coordination of the nutrition support teams is vital to ensure better management and early nutrition intervention in hematological patients.

Monoclonal Antibodies in the Treatment of Diffuse Large B-Cell Lymphoma: Moving beyond Rituximab.

Although rituximab has revolutionized the treatment of diffuse large B-cell lymphoma (DLBCL), a significant proportion of patients experience refractory disease or relapse early after the end of treatment. The lack of effective treatment options in the relapsed/refractory (R/R) setting had made the prognosis of these patients dismal. The initial enthusiasm for novel anti-CD20 antibodies had been short-lived as they failed to prove their superiority to rituximab. Therefore, research has focused on developing novel agents with a unique mechanism of action. Among them, two antibody-drug conjugates, namely polatuzumab vedotin (PolaV) and loncastuximab tesirine, along with tafasitamab, an anti-CD19 bioengineered antibody, have been approved for the treatment of R/R DLBCL. Whereas PolaV has been FDA and EMA approved, EMA has not approved loncastuximab tesirine and tafasitamab yet. Results from randomized trials, as well as real-life data for PolaV have been promising. Novel agents as bispecific antibodies bridging CD3 on T-cells to CD20 have shown very promising results in clinical trials and are expected to gain approval for treatment of R/R DLBCL soon. As the therapeutic armamentarium against DLBCL is expanding, an improvement in survival of patients with R/R and higher cure rates might soon become evident.

Very Early Onset of Therapy-Related Acute Myeloid Leukemia with 11q23 Rearrangement Presenting with Unusual PET Findings after R-DA-EPOCH for Primary Mediastinal Large B-Cell Lymphoma.

BACKGROUND: R-DA-EPOCH is an effective regimen for PMLBCL, which permits the omission of consolidative radiotherapy in the majority of patients. PATIENT: We describe a 27-year-old female patient, who achieved a complete remission after treatment with six cycles of R-DA-EPOCH (up to the final level). At 6 months after the end of treatment, PET/CT revealed an unexpected, diffusely increased 18FDG uptake by the bone marrow. Simultaneously, pancytopenia with monocytosis was observed. RESULT: The patient was diagnosed with therapy-related myelodysplastic syndrome, which rapidly evolved into acute myeloid leukemia (t-MDS/AML) with MLL rearrangements. She achieved a complete remission after induction therapy, received an allogenic transplant and remains disease-free 2 years later. CONCLUSIONS: The extremely early onset of t-MDS/AML, together with the unexpected PET/CT findings make this case unique and highlights the need for the accurate estimation of the possible dose-dependent risk of t-MDS/AML after R-DA-EPOCH in the real-life setting in patients with PMLBCL.

Prognostic Factors and Survival of Gliomatosis Cerebri: A Systematic Review and Meta-Analysis.

BACKGROUND: Gliomatosis cerebri (GC) is a fatal diffusely infiltrating glioma. Because of its rarity, only scarce evidence is available regarding outcome predictors and the proper management of GC. METHODS: Reported studies of patients with histologically confirmed GC were systematically reviewed and individual patient-level data (n = 523) extracted. Multivariable Cox proportional hazard models were fit for overall survival (OS) and progression-free survival (PFS). RESULTS: The median OS and PFS were 13 and 10 months, with 5-year rates of 18% and 13%, respectively. Age ≥65 years at diagnosis (hazard ratio for OS [HROS], 2.32; 95% confidence interval [CI], 1.62-3.31), high-grade tumor (HRPFS for grade III, 1.57; 95% CI, 1.02-2.40; HRPFS for grade IV, 1.74; 95% CI, [0.98-3.10), GC type II (HROS, 1.49; 95% CI, 1.12-1.98; HRPFS, 1.56; 95% CI, 1.04-2.34), more central nervous system (CNS) regions involved (HROS, 1.09; 95% CI, 1.01-1.18), focal neurological deficits (HROS, 1.41; 95% CI, 1.07-1.86), cerebellar symptoms (HRPFS, 2.20; 95% CI, 1.42-3.39), more symptoms at presentation (HROS, 1.21; 95% CI, 1.05-1.40), Karnofsky performance scale score <70 (HROS, 3.58; 95% CI, 1.73-7.39; HRPFS, 4.48; 95% CI, 1.39-14.4), magnetic resonance imaging contrast enhancement (HROS, 1.48; 95% CI, 1.12-1.96; HRPFS, 1.74; 95% CI, 1.18-2.55), symmetric bilateral CNS invasion (HROS, 1.42; 95% CI, 1.03-1.96), and high proliferation index (Ki-67 >5%; HROS, 2.32; 95% CI, 1.11-4.86) were independent predictors of poor outcomes. In contrast, seizure occurrence (HROS, 0.77; 95% CI, 0.60-1.00; HRPFS, 0.68; 95% CI, 0.47-0.95), isocitrate dehydrogenase 1 mutation (HROS, 0.16; 95% CI, 0.05-0.49), and O6-methylguanine-DNA-methyltransferase promoter methylation (HROS, 0.23; 95% CI, 0.09-0.59) were associated with prolonged survival. Chemotherapy and surgical resection were associated with improved outcomes, but radiotherapy, whether monotherapy or combined with chemotherapy, was not superior to chemotherapy alone. CONCLUSIONS: In the largest study to date on GC, we have identified clinical, imaging, and molecular outcome predictors that are similar to other gliomas and highlight the beneficial effect of chemotherapy and surgical resection, when feasible, on outcomes.

Consumption of fruits, vegetables, and risk of hematological malignancies: a systematic review and meta-analysis of prospective studies.

We examined the association between fruit/vegetable consumption and the risk of hematological malignancies in cohort studies (end of search: August 31, 2016). Total fruit consumption was not associated with the risk of non-Hodgkin lymphoma (NHL) (RR = 1.03, 95% CI: 0.92-1.16, I2 = 12.1%, n = 7), acute myeloid leukemia (RR = 1.23, 95% CI: 0.94-1.61, I2 = 0%, n = 3), multiple myeloma (MM; RR = 1.05, 95% CI: 0.72-1.55, I2 = 60.0%, n = 4), and Hodgkin lymphoma. However, citrus fruit consumption was associated with reduced NHL risk (RR = 0.85, 95% CI: 0.73-1.00, p = .044, I2 = 0%, n = 6). Vegetable intake was marginally associated with reduced NHL risk (RR = 0.89, 95% CI: 0.79-1.00, p = .056, I2 = 16.2%, n = 7), but not with acute myeloid leukemia, multiple myeloma, and Hodgkin lymphoma risk. Nevertheless, NHL risk was inversely associated with cruciferous vegetable consumption (RR = 0.84, 95% CI: 0.71-1.00, p = .047, I2 = 0%, n = 3). Notably, combined fruit/vegetable consumption was associated with decreased NHL risk (RR = 0.79, 95% CI: 0.65-0.96, I2 = 11.2%, n = 3). This meta-analysis reveals possible protective effects; however, confounding and reporting bias could have affected the results.

Anthropometrics at birth and risk of a primary central nervous system tumour: A systematic review and meta-analysis.

BACKGROUND: The aetiology of primary central nervous system (CNS) tumours remains largely unknown, but their childhood peak points to perinatal parameters as tentative risk factors. In this meta-analysis, we opted to quantitatively synthesise published evidence on the association between birth anthropometrics and risk of primary CNS tumour. METHODS: Eligible studies were identified via systematic literature review; random-effects meta-analyses were conducted for the effect of birth weight and size-for-gestational-age on childhood and adult primary CNS tumours; subgroup, sensitivity, meta-regression and dose-response by birth weight category analyses were also performed. RESULTS: Forty-one articles, encompassing 53,167 CNS tumour cases, were eligible. Birth weight >4000 g was associated with increased risk of childhood CNS tumour (OR: 1.14, [1.08-1.20]; 22,330 cases). The risk was higher for astrocytoma (OR: 1.22, [1.13-1.31]; 7456 cases) and embryonal tumour (OR: 1.16, [1.04-1.29]; 3574 cases) and non-significant for ependymoma (OR: 1.12, [0.94-1.34]; 1374 cases). Increased odds for a CNS tumour were also noted among large-for-gestational-age children (OR: 1.12, [1.03-1.22]; 10,339 cases), whereas insufficient data for synthesis were identified for other birth anthropometrics. The findings remained robust across subgroup and sensitivity analyses controlling for several sources of bias, whereas no significant heterogeneity or publication bias were documented. The limited available evidence on adults (4 studies) did not reveal significant associations between increasing birth weight (500-g increment) and overall risk CNS tumour (OR: 0.99, [0.98-1.00]; 1091 cases) or glioma (OR: 1.03, [0.98-1.07]; 2052 cases). CONCLUSIONS: This meta-analysis confirms a sizeable association of high birth weight, with childhood CNS tumour risk, particularly astrocytoma and embryonal tumour, which seems to be independent of gestational age. Further research is needed to explore underlying mechanisms, especially modifiable determinants of infant macrosomia, such as gestational diabetes.