Autologous hematopoietic stem cell transplantation treatment for T cell lymphoblastic lymphoma / 中华血液学杂志

Objective: To investigate the efficacy and predictors of autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of T lymphoblastic lymphoma (T-LBL) . Methods: 41 patients with T-LBL who underwent auto-HSCT from April 2006 to July 2017 in the Department of Hematology, the First Affiliated Hospital of Soochow University and the Department of Lymphoma, Peking University Cancer Hospital were analyzed retrospectively. Results: ①Among 41 patients, there were 30 males and 11 females with median age of 24 (11-53) years old. According to the Ann Arbor staging, 33 (80.5%) patients were in stage Ⅲ/Ⅳ. 12 (29.3%) patients have mediastinal involvement, and 20 (48.8%) patients have bone marrow (BM) involvement. Before transplantation, there were 26 (63.4%) patients who achieved first complete remission (CR(1)) , the other 15 (36.6%) patients were in the non-CR(1) group, and there were 29 (70.7%) patients in the low-intermediate risk group (IPI<3 scores) , the other 12 (34.1%) patients were in the middle-high risk group (IPI≥3 scores) . ②The median follow-up was 29 (3-98) months. The 3-year overall survival (OS) and progression-free survival (PFS) for 41 patients were (64.3±8.2) % and (66.0±7.8) %, respectively. 3-year cumulative recurrence rate (CIR) was (30.7±7.4) %, and 3-year non-recurring mortality (NRM) was (4.8±4.6) %. ③The 3-year OS of the CR(1) group and the non-CR(1) group were (83.4±7.6) % and (38.9±12.9) % (P=0.010) , and the 3-year PFS of two groups were (83.8±7.4) % and (40.0±12.6) % (P=0.006) , respectively. The 3-year CIR of these two groups were (16.2±7.4) % and (53.3±12.9) % (P=0.015) , and the 3-year NRM were 0 and (14.3±13.2) % (P=0.157) , respectively. ④The 3-year OS of the IPI low-intermediate risk group and the high-intermediate risk group were (76.9±8.4) % and (35.7±15.2) % (P=0.014) and the 3-year PFS were (77.4±8.2) % and (40.0±14.6) (P=0.011) , respectively. The 3-year CIR of these two groups were (18.1±7.3) % and (60.0±14.6) % (P=0.006) , and the 3-year NRM were (5.6±5.4) % and 0 (P=0.683) , respectively. The OS and PFS of patients with low-intermediate risk group were significantly higher than the other group. Conclusion: Auto-HSCT could improve the survival of T-LBL. Pre-transplant status and IPI score are important predictors for survival T-LBL patients with auto-HSCT.

Prognostic significance of (18)F-fluorodeoxyglucose positron emission tomography in patients with diffuse large B cell lymphoma undergoing autologous stem cell transplantation / 中华血液学杂志

Objective: To evaluate the prognostic value of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in patients with diffuse large B cell lymphoma (DLBCL) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-eight patients with DLBCL treated at Peking University Cancer Hospital between November 2010 and December 2014 were assessed. All patients underwent PET/CT scanning prior to or after auto-HSCT. Correlation analysis was done based upon patients characteristics, PET/CT scan results and survival. Results: ①Among 48 patients, 27 was male, 21 female, median age was 43 (17-59) years old. ② Patients with negative pre-auto-HSCT PET/CT assessment demonstrated significantly better 3-year progression free survival (PFS) (87.1% vs 53.3%, χ(2)=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ(2)=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ(2)=22.75, P=0.001) and OS (97.1% vs 40.0%, χ(2)=21.09, P=0.002) were also significantly different between patients with negative and positive post-auto-HSCT PET/CT assessment. ③ Multivariate analysis indicated a significant association of PFS (HR=13.176, P=0.005) and OS (HR=20.221, P=0.007) with post-auto-HSCT PET/CT assessment. Number of prior treatment regimens was associated with PFS (HR=10.039, P=0.040). ④ Harrell's C index revealed that the value of combined use of number of prior treatment regimens and post-auto-HSCT PET/CT assessment was superior to either one used alone in PFS (Harrell's C values were 0.976, 0.869 and 0.927 in combined use, number of prior treatment regimens and post-auto-HSCT PET/CT assessment, respectively), and the combined use of ECOG performance status and post-auto-HSCT PET/CT assessment significantly increased the Harrell's C index in OS (Harrell's C values were 0.973, 0.711 and 0.919 in combined use, ECOG performance status and post-auto-HSCT PET/CT assessment, respectively). Conclusions: Post-auto-HSCT PET/CT assessment is the main predictor of outcomes in DLBCL patients receiving auto-HSCT. Combined use of post-auto-HSCT PET/CT assessment and number of prior treatment regimens and ECOG performance status is a better prognostic tool in patients with DLBCL undergoing transplantation.

Clinical characteristics and survival analysis of de novo grade 3 or transformed follicular lymphoma patients / 中华血液学杂志

Objective: To evaluate the clinical characteristics and survival outcomes of patients with de novo grade 3 or transformed follicular lymphoma (FL). Methods: Fifty-two patients treated at Peking University Cancer Hospital between January 2009 and September 2017 were assessed, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. Baseline characteristics, survival and prognostic factors were analyzed. Results: ① Twenty-six male and 26 female patients were enrolled, including 28 patients with FL 3A grade, 13 patients with FL 3B grade, 11 patients with transformed FL. ②The 3-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 56.0% and 80.6%, respectively. Patients with international prognostic index (IPI) score 0-1 demonstrated significantly better 3-year PFS (80.3% vs 20.1%; t=18.902, P<0.001) and OS (95.7% vs 57.0%; t=10.406, P<0.001) than patients with IPI score 2-3. Three-year PFS (94.1% vs 37.2% vs 25.2%; P=0.002) and OS (100.0% vs 76.0% vs 59.8%; P=0.020) were also significantly different among patients with FLIPI 1 score 0-1, 2, ≥3. FLIPI 2 score was also identified as a prognostic factor for 3-year PFS (68.4%, 0, 0; P=0.001) and OS(87.5%, 76.2%, 0; P=0.003). ③Multivariate analysis indicated a significant association of PFS (HR=3.536, P=0.015) and OS (HR=15.713, P=0.015) with IPI. FLIPI 2 was associated with OS (score 0-1, HR=0.078, P=0.007; score 2, HR=0.080, P=0.022). Conclusion: De novo grade 3 or transformed FL might be a group of curable disease with current treatment strategies. IPI is still a prognostic tool in this scenario.

Prognostic value of (18)F-FDG PET/CT after first-line treatment in patients with diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the value of (18)F-FDG PET/CT in detecting residual disease and predicting relapse following first-line treatment in patients with diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>The clinical data of 39 patients with DLBCL, who underwent PET/CT scan after first-line treatment, were analyzed retrospectively. Kaplan-Meier method was used to analyze the survival of patients.</p><p><b>RESULTS</b>PET/CT findings were interpreted as negative, mild metabolism and positive. Seventeen patients' PET/CT findings were judged as negative, none of them relapsed with a median follow-up of 24.1 months, 13 were judged as mild metabolism, 2 of them relapsed with a median follow-up of 17.1 months. Of the rest 9 findings were judged as positive with a median follow-up of 16.3 months, 4 patients were considered as disease progression according to clinical manifestations and other radiographic results, 2 patients relapsed at the time points of 13.5 and 6.8 months after PET/CT scan respectively, the other 3 patients were diagnosed as negative by biopsy, none of them relapsed at the time points of 5.9, 9.6 and 20.0 months after PET/CT scan respectively. One-year progression-free-survival (PFS) for negative, mild metabolism and positive groups was 100%, 83% and 56%, respectively. Two-year PFS was 100%, 83% and 42%, respectively. Overall survival (OS) at 1 year for negative, mild metabolism and positive groups was 100%, 100% and 89%, respectively. Two-year OS was 100%, 100% and 63%, respectively (P = 0.004).</p><p><b>CONCLUSION</b>DLBCL patients with negative and mild metabolism PET/CT following first-line treatment had good prognosis, who needed no additional therapy. While patients with positive PET/CT had poor prognosis, those patients should receive biopsy before adjusting treatment regimen because of the high false-positive rate.</p>

The clinical features, therapeutic responses, and prognosis of the patients with mantle cell lymphoma / 癌症

Mantle cell lymphoma(MCL), a special type of non-Hodgkin's lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.

Plasma levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in patients with newly diagnosed lymphomas / 中国实验血液学杂志

The objective of this study was to detect the expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma of newly diagnosed lymphoma patients, and analyze their possible relationships with clinicopathological characteristics and prognosis. The expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma from 86 newly diagnosed lymphoma patients were detected by enzyme-linked immunosorbent assay (ELISA). As a results, the multivariate analysis showed that VEGF-C level in non-Hodgkin's lymphoma patients was low, but high in Hodgkin's lymphoma patients; VEGFR-2 level was higher in patients > 60 years, while VEGF-D level was lower in patients with IPI > 2. The univariate analysis showed that VEGF-D level was lower in patients with IPI > 2, while VEGF-D and VEGF-C levels were higher in patients without B symptoms. Relationship analysis between these factors indicated that the relation of VEGF-D expression level with VEGFR-2 and VEGFR-3 was positive. It is concluded that VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 play important roles in the pathogenesis of lymphoma, and may be used as indicators of prognosis evaluation or even guide for the antiangiogenesis treatment of lymphoma.

An analysis of hepatitis B virus infection rate in 405 cases of non-Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the status of hepatitis B virus (HBV) infection in non-Hodgkin lymphoma (NHL) patients.</p><p><b>METHODS</b>The serum HBV markers in NHL patients were detected by enzyme-linked immunosorbent assay (ELISA). The infection rate of HBV in NHL patients was compared with that in nationwide general population.</p><p><b>RESULTS</b>The positive rates of HBsAg, anti-HBs and anti-HBc in 405 cases of NHL were 11.6%, 39.8% and 47.9%, respectively, which were statistically different from those in general population (P < 0.01). The positive rates of HBsAg, anti-HBs and anti-HBc in B-cell NHL and T-cell NHL were 13.3% vs 7.1% (P = 0.083), 40.6% vs 37.5% (P = 0.567), 53.2% vs 33.9% (P = 0. 001), respectively. The HBV DNA positive rate was 23.7% in 93 cases of NHL, and was 50.0% in 38 cases of HBsAg-positive NHL while 5.5% in 55 cases of HBsAg-negative but HBcAb-positive NHL.</p><p><b>CONCLUSIONS</b>The infection rate of HBV in NHL patients is higher than that in general population, in which occult hepatitis B virus infection can not be ignored. The positive rate of anti-HBc in B-cell NHL is significantly higher than that in T-cell NHL. For NHL patients infected with HBV, prophylactic anti-HBV therapy to prevent viral reactivation should be given before the anti-cancer treatment. Further study in the relationship between HBV and NHL should be carried out in the future.</p>

Regulatory T cells inhibit proliferation of mouse lymphoma cell line EL4 in vitro / 中国实验血液学杂志

This study was aimed to investigate the effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cells and its mechanism in vitro. C57BL/6 mouse Treg cells were isolated by magnetic cell sorting (MACS). The purity of Treg cells and their expression of Foxp3 were identified by flow cytometry (FCM) and PT-PCR respectively. The suppression of Treg cells on EL4 cells was detected by 3H-TdR method. At the same time, enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokine TGF-β1 and IL-10. The results showed that CD4+CD25+ T cells could be successfully isolated by MACS with the purity reaching 94.52% and the expression of Foxp3 reaching 84.72%. After sorting, the expression of Foxp3 mRNA could be detected by RT-PCR. 3H-TdR assay confirmed that regulatory T cells could suppress the proliferation of EL4 cells with or without antigen presenting cells (APC) or dendritic cells (DC), APC or DC might effectively enhance the suppression. In addition, DC alone also suppressed the proliferation. TGF-β1 and IL-10 could be detected in the supernatant by ELISA. It is concluded that the Treg cells can obviously suppress the proliferation of T cell lymphoma cells in vitro, APC or DC can enhance this suppressive effect, while the DC alone also can suppress the proliferation of EL4 cells, the TGF-β1 and IL-10 cytokine pathway may be one of the mechanisms of suppression.

Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro / 中国实验血液学杂志

This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.