Introduction: Extranodal natural killer/T cell lymphoma (ENKTL) nasal type is a rare and highly aggressive subtype of lymphoid neoplasia, with a characteristic epidemiology, predominating in the Asian population and some sites in Latin and Central America. Diagnostic pitfalls and the lack of large randomized trials partly explain the unsatisfactory outcomes reported, even with the recent advances such as the incorporation of asparaginase in the frontline regimens and the description of new prognostic factors. Since few reports from Latin America and non-Asian population are available, we conducted this retrospective study to evaluate clinical characteristics and outcomes in a Brazilian referral center.
Methods: This is a retrospective single-center study, conducted in an academic center in Brazil. All patients diagnosed with ENKTL from May 1993 to March 2019 were included. Staging was performed according to Ann-Arbor classification. Patients were treated based at discretion of the physician. Survival analysis was performed using the Kaplan-Meier method and log-rank test for comparison. Cumulative incidence of relapse (CIR) was calculated using death as a competitor.
Results: A total of 37 patients with ENKTL was included. Median age was 46 years (range, 18 - 84), with male predominance (54%) and Caucasian ethnic majority (87%). Localized disease (Stages I and II) was predominant (81%) and five cases of primary extranasal disease were found. Skin was the most frequent extranasal site affected (60%). Five patients had central nervous system (CNS) disease (3 at diagnosis and 2 during progression/relapse). Tumor site infection at diagnosis was documented in 74%. Only six patients had EBV viral load available at diagnosis, with an median of 650 copies/ml (range, 482 - 997). Other features are summarized in Table 1. Five patients did not receive any regimen (3 subjects died from sepsis before treatment and 2 received only supportive care). Among the treated patients, anthracycline-based regimens (CHOP-like including or not methotrexate) were the most common regimen (16/32, 50%), followed by concomitant chemotherapy/radiotherapy (CCRT) strategy (8/32, 25%). Asparaginase was included in the treatment in 16% of cases (5/32) and 9% received isolated radiotherapy (RT) (3/32). RT was performed in 81%, mostly using sequential strategies (61%). Incidence of febrile neutropenia and grade 3/4 mucositis during treatment was 88% and 65%, respectively. Complete response (CR) rate after the first-line regimen was 62.5% (95% confidence interval [CI]: 43.7 - 78.3) and primary refractory disease was found in 18.7%. Regarding the patients who achieved CR, 5-year CIR was 19.1% (95% CI 6.6 - 36.4). Autologous stem cell transplantation (ASCT) was performed in two cases after achieving a second CR. Median follow-up was 8.7 years, with 5-year OS of 45.9% (95% CI: 31.4 - 67.1) for all patients and 53.9% (95% CI: 38 - 76.5) among the treated group (Figure 1). Albumin level (<3.5 g/dL) at diagnosis was associated with worse PFS (p = 0.011) and OS (p = 0.0057) in the univariate analysis (unadjusted hazard ratio [HR]=5.16 (95% CI 0.06 - 0.60, p = 0.004) (Figure 2 and 3). Sex, staging, age, blood counts, infection at diagnosis, extranasal type, international prognostic index or employed regimen were not associated with outcomes in our cohort.
Conclusion: There are few reports of clinical characteristics and outcomes of ENKTL in the Latin American population. Although the current data show an increase in response and survival rates in localized stages, published reports from non-Asian population still display poor outcomes. Hypoalbuminemia, as previously described, was associated with worse outcomes in our cohort and, along with the higher toxicity and infection rates, denote the challenge of adapting regimens in the Brazilian population. Cooperative multicenter initiatives and prospective strategies are essential to improve outcomes of this rare and poorly described disease in the non-Asian population.
No relevant conflicts of interest to declare.
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