Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers

The treatment of Burkitt lymphoma in adults

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival We also examined risk factors for CNS recurrence Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement First-line regimen selection was unaffected by CNS involvement (P=093) Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 153, 95% confidence interval [CI], 114-206, P=0004) and overall survival (aHR, 162, 95%CI, 118-222, P=0003) The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%) It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 438, 95%CI, 216-887, P<0001) Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R

/pdf/outcomes-of-burkitt-lymphoma-with-central-nervous-system-3ircpnfzmk.pdf

Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study

Genomic studies have revealed molecular mechanisms involved in the pathogenesis of Burkitt's lymphoma, including the ID3/TCF3-dependent centroblast gene expression program, tonic PI3K-AKT-mTOR signaling, and deregulation of cell cycle and apoptosis through mutations in cyclin D3, CDKN2A, or TP53. Unfortunately, these advances have not been translated into treatment, which relies on dose-intense cytotoxic chemotherapy. While most patients achieve long-term survival, options for relapsed/refractory disease are lacking, as Burkitt lymphoma is often excluded from clinical trials of novel approaches. The lower-intensity, dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) regimen constitutes a major advance allowing for treatment of older and HIV-positive patients but needs augmentation to better address the central nervous system involvement. Furthermore, DA-EPOCH-R provides a platform for the study of targeted or immunotherapeutic approaches while de-escalating cytotoxic agents and their associated adverse effects. In this review we discuss the epidemiology and molecular genetics of BL, first-line treatment considerations, and potential novel treatment strategies.

Burkitt lymphoma: bridging the gap between advances in molecular biology and therapy.

A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double-hit lymphoma (n = 1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI = 60-80%) and 75% (95% CI = 66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.

A dose-dense short-term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high-risk Burkitt lymphoma or high-grade B-cell lymphoma: safety and efficacy results of the "CARMEN" phase II trial.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1–2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Munster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14–74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.

/pdf/treatment-of-sporadic-burkitt-lymphoma-in-adults-a-1y5ywyek0s.pdf

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens

Polyostotic DLBCL Is Characterized By a NF-Κb Pathway Affecting Molecular Profile and Superior Survival

BACKGROUND
Restrictive red blood cell transfusion strategies are widely recommended for acute anemia but may not adequately address the needs of chronically anemic patients with transfusion-dependent myelodysplastic syndromes or myeloproliferative neoplasms. For these patients with chronic anemia, alleviating symptoms and improving quality of life are key objectives. This study evaluates the impact of additional red blood cell (RBC) transfusions administered alongside standard-of-care transfusions on heart rate, physical activity, quality of life, and cognitive function.


STUDY DESIGN AND METHODS
This interim analysis of a randomized, multicenter, within-subject, cross-over trial evaluated 12 transfusion-dependent patients receiving three transfusion regimens: standard-of-care, standard-of-care + 1 additional unit, and standard-of-care + 2 additional units. The primary outcome was heart rate, and secondary outcomes were physical activity, quality of life, and cognitive performance. Heart rate and activity were continuously monitored, while questionnaires and cognitive tasks assessed outcomes at predefined visits.


RESULTS
Greater hemoglobin augmentation was associated with significant reductions in heart rate, with the largest decrease in patients receiving the standard-of-care + 2 regimen. Quality of life and fatigue measures showed transient improvements with more red blood cells transfused, though these changes were not statistically significant. Cognitive performance trends suggested possible benefits, but findings were inconsistent. Physical activity, as measured by daily step count, was unaffected by transfusions.


CONCLUSIONS
This interim analysis suggests that higher post-transfusion hemoglobin is associated with lower heart rate, reflecting enhanced oxygen delivery. Wearable monitoring was sensitive to these changes. Nonsignificant, hypothesis-generating trends toward improved QoL, fatigue, and cognition were observed.

Heart rate changes in chronically red cell transfusion-dependent patients-A dose-dependent effect of red cell transfusion: A randomized cross-over trial, interim analysis.

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Papers

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens

Polyostotic DLBCL Is Characterized By a NF-Κb Pathway Affecting Molecular Profile and Superior Survival

Heart rate changes in chronically red cell transfusion-dependent patients-A dose-dependent effect of red cell transfusion: A randomized cross-over trial, interim analysis.