Prediction and prevention of central nervous system relapse in patients with extranodal natural killer/T-cell lymphoma

Abstract

Since non-anthracycline-based chemotherapy with L-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose MTX (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into two groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new CNS-PINK model was developed using one-point powerful predictors of CNS relapse [the prognostic index of natural killer lymphoma (PINK); HR: 2.908; P = .030 and extranodal involvement (≥ 2); HR: 4.161; P = .001] and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation cohort (P = .038). Patients in the high-risk CNS-PINK group who received SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effect of S-ID-MTX for preventing CNS events in high-risk CNS-PINK patients should be verified by future studies.

Extranodal NK/T-Cell Lymphoma Occurring Primarily in the Eyes and with Central Nervous System Relapse

“…Recently, Kim et al proposed a central nervous system-prognostic index of natural killer (CNS-PINK) model to predict CNS relapse in patients with ENKTL. 14 This model included the intermediate/high prognostic index of natural killer (PINK) score and extranodal involvement≥2 as predictors of CNS relapse, with 1 point for each factor. 3 , 14 Patients with these two factors were at high risk of CNS relapse, with a 2-year CNS risk of 22.8%.…”

“… 14 This model included the intermediate/high prognostic index of natural killer (PINK) score and extranodal involvement≥2 as predictors of CNS relapse, with 1 point for each factor. 3 , 14 Patients with these two factors were at high risk of CNS relapse, with a 2-year CNS risk of 22.8%. The PINK score of this patient was 2 (high risk) with > 2 extranodal involvement, which is stratified as having a high risk of CNS relapse in this model.…”

Association of improved overall survival with decreased distant metastasis following asparaginase-based chemotherapy and radiotherapy for intermediate- and high-risk early-stage extranodal nasal-type NK/T-cell lymphoma: a CLCG study

“…8 Thus, our results may not be applicable to patients receiving ASP/MTX-based regimens. However, given the severe toxicities 9,10,14 and low risk of central nervous system involvement, 51 the role of incorporation of MTX into ASP-based regimens remains uncertain for the first-line CMT of early-stage ENKTCL. Using PFS at 24 months as an efficacy endpoint, 52 further work is needed to optimize systemic therapies or novel regimens with inclusion of ASP and radiotherapy in intermediate-and high-risk early-stage patients.…”

Is the CNS-PINK the new CNS risk model in ENKTL?

“…In this issue of Blood, Kim and colleagues sought to develop a much needed clinical predictor of central nervous system (CNS) relapse in extranodal natural killer (NK)/T-cell lymphoma (ENKTL). 1 Because CNS relapse in lymphomas is an uncommon but often devastating event, recent efforts have focused on the identification of high-risk patients to consider for CNS diagnostic tests and upfront treatment modifications.…”

“…All cases were Epstein-Barr virus positive by local review, and treatment integrated a nonanthracycline-based regimen. 1 A separate "validation" cohort consisted of 253 ENKTL Japanese patients. 9…”