Optimal treatment strategies for localized extranodal natural killer/T cell lymphoma (ENKTL) have not been fully defined. We retrospectively compared the efficacy and safety of combined gemcitabine, L-asparaginase, and oxaliplatin (GELOX) (n=38), continuous infusion of etoposide, vincristine and doxorubicin, with cyclophosphamide and prednisone (EPOCH) (n=54), or combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n=135) as induction chemotherapy in patients who were newly diagnosed with stage I/II ENKTL. After induction chemotherapy, the complete response (CR) rate and overall response rate (ORR) for the GELOX group were significantly higher than those in the EPOCH group (68.4 vs. 42.6%, P=0.011 for CR and 86.8 vs. 68.5%, P=0.038 for ORR). Both EPOCH and GELOX groups can attain much higher CR rates than CHOP group (CR rate was 31.8%, P<0.05). The 3-year overall survival (OS) and progression-free survival (PFS) rate were significantly better in GELOX group than in EPOCH or CHOP group (87.0 vs. 54.0 vs. 54.0% for OS, P<0.05; 72.0 vs. 50.0 vs. 43.0% for PFS, P<0.05). However, no significant differences were found between EPOCH and CHOP groups in OS or PFS (P=0.765 for OS, and 0.421 for PFS). The safety profiles were acceptable in all three groups. In conclusion, GELOX is superior to EPOCH or CHOP in the treatment of patients with stage I/II ENKTL. Further clinical trials of ENKTL should use asparaginase-based regimens as the standard chemotherapy.
Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38–51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.
A broadly accepted standard treatment for adult T-lymphoblastic lymphoma (T-LBL) has not yet been defined. To address that issue, we retrospectively compared three chemotherapy regimens used to treat 110 adult patients with newly diagnosed T-LBL. These included two adult regimens (ECOG2993 and hyper-CVAD) and a childhood regimen (BFM-90). These intensive drug regimens are mainly used to treat childhood and adult acute lymphoblastic leukemia. They included induction, consolidation, and maintenance chemotherapy protocols and were administered over the course of 2 years. Seventy-five patients (80%) achieved a complete remission (CR). Within a median follow-up time of 31 months (range: 5–152 months), the 5-year overall survival (OS) and progression-free survival (PFS) rates were 47.7% (95% CI, 35.0–69.8%) and 45.7% (95% CI, 27.6–56.6%), respectively. Shorter survival was associated with age > 40 years, poor ECOG PS and bone marrow involvement. Elevated lactic dehydrogenase (LDH) level, Ann Arbor stage and International Prognostic Index (IPI) score had no prognostic value. The childhood chemotherapy regimen improved CR and the overall survival rate more than the adult regimen in patients aged < 40 years.
The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL.
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