Research On Treatment And Prognosis Of Diffuse Large B-cell Lymphoma And T/NK Cell Lymphoma

Lymphoma is one of the most common malignant tumors in China. For the reason that the pathological subtypes are complex, standard treatment has not been established for some subtypes. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non Hodgkin’s lymphoma (NHL). The treatment is still controversial for some subtypes with primary tumors located in special sites such as primary testicular DLBCL. The role of rituximab in the treatment of stage I DLBCL patients remains to be defined. Peripheral T cell lymphoma (PTCL) and extranodal NK/T cell lymphoma (ENKL) are relatively rare subtypes of NHL, which are more common in China than in western countries. There is a lack of standard treatment with poor prognosis. In this study, we aim to assess the treatment and prognosis of DLBCL and T/NK cell lymphoma, and the main contents are mainly divided into two parts.Part 1. Research on treatment and prognosis of diffuse large B-cell lymphomaChapter 1. The role of rituximab and radiotherapy in the treatment of stage I diffuse large B-cell lymphomaObjective:The role of rituximab and radiotherapy in the treatment of stage I DLBCL patients remains to be defined.Methods:Between 2003 and 2009,140 untreated patients with stage I DLBCL were retrospectively analyzed in this study.Results:Complete response (CR) rate was 77% both in R-CHOP (n=62) and CHOP (n=78) groups (P=0.945). Patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs.85%; P=0.215) and 5-year overall survival (OS) (90% vs.96%;P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs.71%; P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS.Conclusions:CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I DLBCL patients.Chapter 2. Clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphomaObjective:To assess the clinical features, survival and prognostic factors of primary testicular DLBCL.Methods:A retrospective study of 37 patients with primary testicular DLBCL was carried out from 2003 to 2012.Results:The median PFS was 26.2 months and the 3-year OS rate was 78.4%. There was a trend toward superior outcome for patients who received combined therapy (Surgery/Chemotherapy/Radiotherapy) (P=0.055). Patients who had CR, primary tumor diameter< 7.5cm and IPI≤1 were significantly associated with longer PFS at multivariate analysis.Conclusions:Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of surgery, doxorubicin contained chemotherapy and contralateral testicular radiotherapy seemed to improve survival.Part 2. Research on treatment and prognosis of NK/T cell lymphomaChapter 1. Treatment outcome and prognostic factors for stage IE/IIE extranodal natural killer/T-cell lymphomaObjective:Optimal treatment modalities and prognostic factors for localized ENKL have not been fully established.Methods:This study aimed to evaluate the best treatment strategy and prognostic factors for 305 localized ENKL patients between 2003 and 2013.Results:The CR rate for patients received chemoradiotherapy (n=175) was significantly higher than that for patients received radiotherapy alone (n=102) (89.1 vs.77.5%, P = 0.009) or chemotherapy alone (n=14) (89.1 vs.21.4%, P<0.001). The 3-year OS of 228 stage IE paranasal extension or ⅡE patients received combined chemoradiotherapy (n=154), radiotherapy alone (n=60) and chemotherapy alone (n=14) were 85.7%,73.3% and 57.1% respectively (chemoradiotherapy vs. radiotherapy, .P=0.003; chemoradiotherapy vs. chemotherapy, P< 0.001). For patients received combined chemoradiotherapy, the GDP regimen (n=54) could significantly improve 3-year PFS compared with the CHOP regimen (n=110) (88.9% vs.70.9%, P=0.022). Patients received radiotherapy first followed by chemotherapy (n=84) was associated with superior 3-year PFS compared with patients received chemotherapy first (n=96) (81.0% vs.69.8%, P=0.055). However, induction chemotherapy (n=17) was shown to increase 3-year PFS (100.0% vs.83.8%, P=0.112) and OS (100.0% vs.86.5%, P=0.180) in 54 patients treated with GDP regimen. We identified 3 risk groups with different survival outcomes based on 3 prognostic factors (stage II, elevated LDH and paranasal extension). The 3-year OS rates were 93.5%,85.0% and 62.2% respectively for patients with no risk factors,1 or 2 factors, and 3 factors (P<0.001).Conclusion:Combined chemoradiotherapy is the most optimal therapy strategy for stage IE paranasal extension or HE ENKL patients. GDP or GDP combined with pegaspargase regimen showed promising efficacy. Stage II, elevated LDH and paranasal extension could be the most significant poor prognostic factors for ENKL patients with limited stage.Chapter 2. Comparison of CHOP, CHOPE and GDP in the first-line treatment of peripheral T cell lymphomaObjectives:Optimal chemotherapy regimen for PTCL have not been fully defined.Methods:Between 2003 and 2014,93 consecutive patients with PTCL were retrospectively analyzed in this study.Results:The CR rate for patients received CHOP (n=38), CHOPE (n=39), and GDP (n=11) were 28.9%,51.3%, and 45.5% respectively (P=0.132) with an ORR of 65.8%, 76.9%, and 90.9% respectively (P=0.210). Median PFS in CHOP (n=40), CHOPE (n=42), and GDP (n=11) groups were 6.0,15.3, and 9.7 months (P=0.094) with 1-year PFS of 35.0%,54.8% and 45.5% respectively(P=0.078).1-year OS for patients received CHOP (n=40), CHOPE (n=42), and GDP (n=11) were 65.0%,83.3%, and 100% respectively (P=0.013) (CHOP vs CHOPE, P=0.030; CHOP vs GDP,P=0.024; CHOPE vs GDP, P=0.174). There was no significant difference of grade 3-4 adverse events in three groups.Conclusion:CHOPE has a trend to improve CR rate,1-year PFS and significantly improve OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies.