Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project

Purpose To explore a more effective treatment for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKL), we conducted a phase II study of the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen. Patients and Methods Patients with newly diagnosed stage IV, relapsed, or refractory disease and a performance status of 0 to 2 were eligible. Two cycles of SMILE chemotherapy were administered as the protocol treatment. The primary end point was the overall response rate (ORR) after the protocol treatment. Results A total of 38 eligible patients were enrolled. The median age was 47 years (range, 16 to 67 years), and the male:female ratio was 21:17. The disease status was newly diagnosed stage IV in 20 patients, first relapse in 14 patients, and primary refractory in four patients. The eligibility was revised to include lymphocyte counts of 500/μL or more because the first two patients died from infections. No tre...

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2011.35.6287

Phase II Study of SMILE Chemotherapy for Newly Diagnosed Stage IV, Relapsed, or Refractory Extranodal Natural Killer (NK)/T-Cell Lymphoma, Nasal Type: The NK-Cell Tumor Study Group Study

[Extranodal NK/T-cell lymphoma, nasal type].

Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15-69 years of age, and had satisfactory performance scores (0-2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.2008.00768.x

Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia.

Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22). At the time of HSCT, 22 patients were in complete remission (CR), 11 were in relapse, and seven were primary refractory. All patients received myeloablative conditioning regimens including total-body irradiation. Sixteen died of disease progression, and six of treatment-related causes. Overall, 4-year survival was 39% with a median follow-up of 50 months; this was significantly better than that of patients who did not undergo HSCT (21%, P = 0.0003). For patients transplanted in CR, the 4-year overall survival was 68%, which was significantly better than that of patients who went into CR but did not undergo HSCT (P = 0.03). These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage.

H. Mukai

Papers

Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms.