This protocol applies to fit patients diagnosed with localised, limited-stage extranodal NK/T-cell lymphoma (stage I or II) who are able to tolerate chemotherapy and are eligible for haematopoietic stem-cell transplantation (HSCT).
The patient is fit, with disease confined to limited stage (I–II), and is a candidate for combined modality treatment. HSCT eligibility is a defining feature of this scenario and directly shapes the treatment regimen selected.
The approach combines involved-site radiotherapy with an anthracycline-free, L-asparaginase-containing chemotherapy regimen — the full protocol details timing, scheduling options, substitution in the event of L-asparaginase hypersensitivity, and criteria for consolidative HSCT in responding high-risk patients.
EBV DNA in peripheral blood serves as a key biomarker of treatment response and is monitored alongside imaging-based assessment throughout therapy.
DOI: 10.1016/j.annonc.2025.01.023
For fit patients with localised stage I–II disease, concomitant, interposed ('sandwich schedule') or rapidly sequential chemoradiotherapy (CRT), with an early RT dose of 50 Gy and a platinum- and/or L-asparaginase-containing regimen, have been applied.
Fit patients with limited-stage disease should receive ISRT (50 Gy) with concurrent, interposed or sequential anthracycline-free, L-asparaginase-containing ChT [e.g. DDGP or modified SMILE (mSMILE) for HSCT-eligible and AspMetDex or P-GEMOX for HSCT-ineligible patients] [II, A].
If available, crisantaspase (Erwinia chrysanthemi-derived L-asparaginase) is recommended for patients who have developed hypersensitivity or inactivating antibodies to Escherichia coli-derived L-asparaginase [III, A; not EMA or FDA approved in ENKTCL].
In HSCT-eligible responding high-risk patients, consolidative auto- or allo-HSCT can be considered [III, B].
EBV DNA in peripheral blood should be monitored by quantitative PCR at baseline and during therapy as a biomarker of response, in addition to imaging-based response assessment [II, A].
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