DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients

Clin Transl Sci. 2021 Jan;14(1):405-411. doi: 10.1111/cts.12893. Epub 2020 Oct 12.


Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare peripheral T-cell lymphoma that predominantly occurs in Asian and South American populations. The treatment of ENKL has been a challenge for a long time. This study was conducted to compare the clinical efficacy and safety of cisplatin, dexamethasone, gemcitabine, and pegaspargase (DDGP) and methotrexate, dexamethasone, ifosfamide, L-asparaginase, and etoposide (SMILE) regimens for relapsed/refractory ENKL and explore the prognostic factors. From October 2014 to July 2019, 54 patients with relapsed/refractory ENKL who received DDGP or SMILE chemotherapy were retrospectively assessed in this study. Thirty-one patients received DDGP chemotherapy and 23 patients received SMILE chemotherapy. A higher complete response rate was observed in patients treated with DDGP regimen (61.3% vs. 30.4%, P = 0.025). The DDGP group (95% confidence interval (CI) of 5-year progression-free survival (PFS): 24.6-66.2%; 95% CI of 5-year overall survival (OS): 8.5-91.7%) was also significantly associated with longer 5-year PFS and 5-year OS (P = 0.008 for 5-year PFS, P = 0.023 for 5-year OS). More serious leucopenia (P = 0.021), neutropenia (P = 0.041), and allergy (P = 0.040) were observed in the SMILE group. Post-treatment Epstein-Barr virus (EBV)-DNA status (P = 0.001 for PFS, P = 0.018 for OS) was identified as a significant prognostic factor for PFS and OS in multivariate analysis. The present research suggested that compared with SMILE chemotherapy, DDGP chemotherapy can significantly improve the response and survival of relapsed/refractory ENKL with better tolerance. Post-treatment EBV-DNA status was identified as a significant prognostic factor for PFS and OS in relapsed/refractory ENKL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • DNA, Viral / isolation & purification
  • Drug Resistance, Neoplasm
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / mortality
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology
  • Female
  • Follow-Up Studies
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Lymphoma, Extranodal NK-T-Cell / drug therapy*
  • Lymphoma, Extranodal NK-T-Cell / mortality
  • Lymphoma, Extranodal NK-T-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / virology
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies
  • Risk Factors
  • Young Adult


  • DNA, Viral