Gemcitabine, L-Asparaginase, Ifosfamide, Dexamethasone and Etoposide (GLIDE) Regiment In Advanced or Refractory Aggressive NK/T Cell Lymphomas: A Pilot Study

Extra nodal NK/T cell lymphoma, nasal type (ENKL) with advanced stage and aggressive NK-cell leukemia (ANKL) are highly aggressive neoplasm with a dismal clinical outcome. Both of these diseases presented with rapid progressed clinical course and resistant to chemotherapy regimens such as CHOP(cyclophosphamide, doxorubicin, vincristine and prednisone). Expression of multi-drug resistance (MDR) associated P-glycoprotein of NK/T cell neoplasms which actively exports many anti-tumor agents outside the tumor cells is one of the well-studied mechanisms. Our new chemotherapeutic regimen GLIDE (Gemcitabine, L-asparaginase, Isofosfomide, Dexamethasone and Epotoside) showed promising results.

From 2010–2011, 3 cases of newly diagnosed ENKL,1 case of newly diagnosed ANKL, and 3 cases of refractory ENKL were enrolled. Former treatments included at least 2–6 cycles of chemotherapy (CHOP or L-asparaginase containing regimens) and local radiotherapy. All of these patients received chemotherapy of GLIDE regimen(Gemcibabine 1000mg/m̂2 D1,8; L-asparaginase 6000u/m̂2 D4,6,8,10,12; Isofosfomaide 1000mg/m̂2 D1-3;Dexamethasone 20mg D1-4; Epotoside 100mg/m̂2 D1-3).The stage of all patients was IV. IPI scores were all in high risk. All patients provided informed written consents and this trial was registered at http://www.chictr.org (ChiCTR-TNC-10000782)

The median age was 41 years (range, 23–54 years);and male (n = 2) to female (n = 5) was 1:2.5. 4 patients finished all 6 cycles, with 3 in CR and 1 in PR; 1 patient died of progression of disease after 2 cycles; 1 patient died of infection in nCR and 1 patient just finished cycle 2 with PR. The OR (CR+nCR+PR) was 85%. The major toxicity of GLIDE were grade 3/4 leucopenia (70.1%, 22 of 31 cycles), and infection (36.3%, 12 of 31 cycles) with 1 death. The non-hematologic toxicity was tolerable, and the hepatic toxicity-associated with the use of L-asparaginase was frequent (42.9%, 3 of 7 patients). However, the majority of the hepatic toxicities were grade 1 or 2.

GLIDE chemotherapy can be an effective treatment strategy with acceptable toxicity in advanced stage or refractory ENKL and ANKL.

No relevant conflicts of interest to declare.