Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

PURPOSE Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

To the editor, Encouraging seroconversion rates to SARS-CoV-2 vaccination in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients have been reported in large cohort studies [1][2][3][4] ; however, the majority of these patients were not receiving active systemic anti-cancer therapy (SACT) and its impact on vaccine responses remains to be fully elucidated. Mori et al. 5 report seroconversion rates of 94.7 and 100% respectively in Japanese patients with AML and MDS after two doses of mRNA SARS-CoV-2 vaccine, of which 39% received SACT. We report SARS-CoV-2 antibody responses following vaccination in a UK cohort of AML and HR-MDS patients all receiving, or having recently completed SACT, and stratified by prior SARS-CoV-2 infection. Demographics, SACT history and laboratory parameters were collected from the electronic health records of patients following two doses of SARS-CoV-2 vaccine (BNT162b2 or ChAdOx1nCoV-19) between December 2020 and July 2021. Serological testing was performed using Roche Elecsys anti-SARS-CoV-2 enzyme immunoassays. A total of 39 patients (85% AML, 15% HR-MDS, median age 63 ), underwent serological testing after receiving two doses of vaccine (Table 1). All were tested for anti-S antibodies after two doses (median 40 days post-dose) and 59% after the first dose (median 39 days). Thirty-three patients (85%) underwent testing for anti-N antibodies, and seven (21% of those tested) had previous SARS-CoV-2 infection. Eleven patients (28%) received intensive chemotherapy, 51% venetoclax-combination therapy (with azacitidine, low-dose cytarabine or gilteritinib) and 21% non-intensive azacitidine. Seropositivity rates and antibody titres increased with consecutive vaccine doses, from 74% in all patients (75% AML, 67% MDS) to 95% (94% AML, 100% MDS), with a median anti-S titre of 5.90 U/ml (IQR 0.58-56.7) after dose one, rising to 333 U/ml (IQR 86.8-1971) post dose two. Significantly higher titres were detected after dose two in AML patients, but not in MDS, though numbers are small (Figure 1B). We report similar seroconversion rates following two doses as seen by Mori et al. (Figure 1A, Table 1), despite all our patients receiving SACT compared to 39% of their cohort; however, we found no difference in anti-S titres between AML and HR-MDS patients receiving SACT after