Peripheral T-Cell Lymphoma-Unspecified (PTCL-U) and NK/T-Cell Lymphoma Showed a Significantly Poor Prognosis in a Randomized Controlled Trial (RCT) JCOG9002 with Multidrug Combination Chemotherapy for Aggressive Lymphoma.
Authors: Kinoshita Tomohiro , Hotta Tomomitsu , Shibata Taro , Mukai Kiyoshi , Yamaguchi Motoko , Tsukasaki Kunihiro , Kagami Yoshitoyo , Kasai Masaharu , Tobinai Kensei , Shimoyama Masanori 
Published: October 2019

Abstract
PURPOSE: To elucidate clinical features of NHL subtyped with WHO classification, and to evaluate the prognostic impact of WHO classification on aggressive lymphoma treated in an RCT.
METHODS: JCOG9002 was an RCT comparing two multidrug combination chemotherapy regimens, LSG9 and mLSG4 (Int J Hematol 80:341, 2004). Major eligibility criteria were; previously untreated patients with intermediate- or high-grade NHL on WF (ATL, LbL and CTCL were excluded); CS I to IV except CS I in GI, thyroid, orbit, or Waldeyer; age 15–69. Tissue specimens were centrally reviewed by six hematopathologists and classified according to WHO classification of lymphoid tumors. Overall survival (OAS) and complete response rate (%CR) of each WHO category were analyzed. Multivariate analyses of prognostic factors influencing OAS were conducted.
RESULTS: A total of 447 patients were registered between 1991 and 1995, and the central pathological review was conducted on 404 patients. Characteristics of the 404 pts include median (range) age 56 (18–69) years; male/female 63/37%, CS I+II/III+IV 31/69%; LDH N/>N 51/49%; PS 0+1/2–4 78/22%; No. of extranodal sites 0–1/1< 77/23%; IPI L/LI/HI/H 40/27/20/12%. Major clinical features, OAS and %CR of major types according to WHO classification are summarized in Table 1. Twelve patients with FL (G1+2) were ineligible in this study but included. Clinical features, response to treatment and prognosis of each subtypes showed distinct patterns. Besides, we found that PTCL-U and NK/T-cell lymphoma showed lower CR rate and poorer OAS, and these features were quite different from other PTCL such as AILT or ALCL. Clinical features in other subtypes were similar to previous reports (Blood89: 3909, 1997; J Clin Oncol16: 2780, 1998). Cox regression analysis with IPI and WHO classification in 366 pts without missing value revealed that PTCL-U and NK/T-cell lymphoma were significant prognostic factors independent from IPI. Hazard ratios of these subgroups vs IPI low risk DLBCL group are 2.66 (95% confidence interval: 1.58–4.48) and 3.21 (1.40–7.37).
CONCLUSIONS: Patients with aggressive lymphoma subtyped according to the WHO classification who were treated in an RCT showed distinctive clinical features. PTCL-U and NK/T-cell lymphoma showed a significantly poor prognosis independent from IPI, warranting further investigations focusing on these two subtypes.
Table 1 No of cases (%) % male Median age % stage III or IV % IPI HI/H %5-yr OAS % CR *Pts with missing value are excluded from the denominator. Only major subtypes are included in this table. DLBCL 242 (59.9) 61 58 63 37 55 71 FL, all grades 37 (9.2) 70 55 68 15 76 70 MCL 15 (3.7) 60 57 87 20 53 73 MZL 9 (2.2) 56 51 71 0 89 67 AILT 22 (5.4) 77 58 100 67 67 73 PTCL-U 23 (5.7) 65 51 83 38 22 43 ALCL 10 (2.5) 70 50 70 33 70 70 NK/T 10 (2.5) 80 52 70 25 40 40