Progress of chimeric antigen receptor T-cell in treatment of lymphoma / 白血病·淋巴瘤

Chimeric antigen receptor T-cell (CAR-T) has changed the treatment landscape of lymphoma. Plenty of research progresses have been made at 63rd annual meeting of American Society of Hematology. Studies with long-term follow-up indicated that CD19 CAR-T is expected to cure 30%-40% of relapsed or refractory large B-cell lymphoma (LBCL). A few studies indicated that CD19 CAR-T would be applied in the second-line or first-line therapy for LBCL. Real world studies further confirmed the efficacy and safety of CD19 CAR-T in treatment of relapsed or refractory follicular lymphoma and mantle cell lymphoma. CAR-T therapy has a promising prospect in the cinical application.

The whole process management principles of chimeric antigen receptor T-cell therapy for lymphoma at Peking University Cancer Hospital / 白血病·淋巴瘤

Chimeric antigen receptor T (CAR-T) cell has achieved excellent efficacy in hematological tumors, especially for lymphoma. Many products have been approved to market all over the world, and 2 products targeting CD19 have been approved to treat relapsed and refractory large B-cell lymphoma in China. The current experiences of using CAR-T cells come from previous clinical studies. How to use CAR-T cells in a standardized and rationalized way is still a challenge faced by our clinicians. Based on the CAR-T cell treatment experiences from Peking University Cancer Hospital and the latest research progresses in CAR-T in China and abroad, this article will elaborate on patient screening, peripheral blood mononuclear cell collection, bridging treatment, lymphocyte depletion chemotherapy, CAR-T cell infusion, the monitoring and treatment of adverse events after infusion, and long-term follow-up after infusion, in order to guide clinicians to better use CAR-T cell and to bring maximum benefits to patients.

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 significance of 18F-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 18F-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%, χ2=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ2=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ2=22.75, P=0.001) and OS (97.1% vs 40.0%, χ2=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 features, diagnosis, treatment, and prognosis of 99 cases with primary intestinal lymphoma / 中华血液学杂志

Objective@#To investigate the clinical features, diagnosis, treatment and prognosis of primary intestinal lymphoma (PIL) .@*Methods@#The characteristics, diagnosis, treatment methods, and follow-up outcomes of 99 PIL patients, diagnosed in Peking university cancer hospital between Nov.1,1995 and Nov. 30, 2013.@*Results@#There were 65 males and 34 females with a median age of 50 years. The majority of clinical manifestation were non-specific gastrointestinal symptoms, 67.68% of cases presented abdominal pain, 26.26% with acute abdomen. The most common primary sites of ileum and ileocecus were identified in 21 cases, respectively. The positive rate of endoscopic was only 24.24%, and 69 cases were diagnosed by operation. 71 patients (71.72%) were stageⅠ-Ⅱand 28 patients (28.28%) were stage Ⅳ. Hodgkin’s lymphoma was not found in all patients. Of the 99 cases, 77 were B-cell origin (77.78%) and 22 were T-cell origin. 55 cases (55.56%) were diagnosed with diffuse large B cell lymphoma (DLBCL) . 60 cases presented IPI score 0-1 point. The median overall survival (OS) was 100.0 months, and 5 year overall survival (5y-OS) was 53.5%. By multiple-factors analysis, T-cell origin lymphoma was significantly correlated with poor prognosis (P<0.05) . There was no difference of the median OS between the patients with operation and chemotherapy alone (79.0 vs 123.0 months, P=0.616) .@*Conclusion@#PIL is commonly seen in males. Abdominal pain is the most common clinical manifestations and the most primary sites are ileum and ileocecus. The diagnosis value of the endoscopic is limited. DLBCL is the most common pathologic type of PIL. T-cell origin lymphoma is an independent prognostic factor for PIL. Surgery is still commonly used in the diagnosis and treatment of PIL, and the operation do not increase the risk of death of patients with PIL.

Updates in chimeric antigen receptor T-cell therapy for lymphoma / 白血病·淋巴瘤

Tremendous success has emerged in chimeric antigen receptor (CAR)-T cell therapy over the past few years, especially in leukemia and lymphoma. The first CAR-T cell product might be available in America in 2017 due to the emergence of the critical results. This paper focused on the key data presented at the 58th American Society of Hematology Annual Meeting.

Comparison of prognostic models for patients with early-stage diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the prognostic value of different models in patients with early-stage diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Early-stage DLBCL patients diagnosed from January 2000 to December 2012 were analyzed retrospectively. All patients received with at least 2 cycles of immunochemotherapy R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with or without radiotherapy. The prognostic value of international prognostic index (IPI) , revised IPI (R-IPI) and enhanced IPI (NCCN-IPI) was compared.</p><p><b>RESULTS</b>Ninety-seven cases of early-stage DLBCL were included in the study. The median age was 58 years (15-88 years) with a median follow-up of 34.7 months (range 7.3-77.4 months). The expected 5-year overall survival (OS) for entire group was 82%. There was no patient in the high risk group according to IPI or NCCN-IPI. According to IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 95%, 38% and 60%, respectively. According to R-IPI, the 5-year OS in the very good, good, and poor risk groups were 93%, 75% and 60%, respectively. According to NCCN-IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 92%, 85% and 29%, respectively.</p><p><b>CONCLUSION</b>NCCN-IPI would be of an ideal prognostic model for early-stage DLBCL patients.</p>

The prognosis value of early and interim ¹⁸F-FDG-PET/CT scans in patients with diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognosis value of early and interim ¹⁸F-FDG-PET/CT scan in patients with diffuse large B- cell lymphoma （DLBCL） to establish the suitable criteria for evaluating posttherapeutic lesions in scans.</p><p><b>METHODS</b>Fifty- six newly diagnosed DLBCL patients were enrolled in the study, and underwent baseline, early and interim ¹⁸F- FDG PET/CT scans. Five- point and % ΔSUVmax criteria were used separately to interpret ¹⁸F- FDG PET/CT images. Interobserver reproducibility was assessed with the kappa test（κ）, and thresholds of %ΔSUVmax were calculated via receiver operating characteristic curve（ROC）. Survival curves were obtained using Kaplan-Meier curves and log-rank test. Cox regression analysis was used for multi-factor analysis.</p><p><b>RESULTS</b>Median follow-up was 24 months（6 to 42 months）. The kappa value of the five- point scale was above 0.600 with the reference background set in the liver（Score≥4）. The optimal threshold of %ΔSUVmax was 81% for early PET/CT and 74% for interim PET/CT. Survival analysis showed both early and interim PET/CT scans could predict the outcome of 56 patients with DLBCL, and 3-year PFS and OS of PET-negative patients were significantly higher than those of PET-positive ones（P<0.05）. Five-score criteria were more accurate in evaluating 3- year PFS of DLBCL patients in the interim PET/CT scan（76.79%）. %ΔSUVmax criteria were better for interpreting 3-year OS（76.79% and 83.93%）. Multi-factor analysis demonstrated that early and interim PET/CT were solid predicting factors for DLBCL patients.</p><p><b>CONCLUSION</b>Early and interim PET/CT scans could predict the outcome of patients with DLBCL, treated with R-CHOP/CHOP. Three-year OS was more accurate in early and interim PET/CT using 66 %ΔSUVmax criteria as an interpretation, while 3-year PFS was more accurate in interim PET/CT by five scores criteria.</p>

Non-upper aerodigestive tract NK/T- cell lymphoma: an analysis of clinical features and survival from a single center in China / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze clinical features and outcomes of non-upper aerodigestive tract NK/T-cell lymphoma (NUAT-NKTCL).</p><p><b>METHODS</b>Clinical data of 44 patients with NUAT-NKTCL diagnosed at Peking University Cancer Hospital between 1999 and 2013 were retrospectively analyzed.</p><p><b>RESULTS</b>Of the 44 patients, there were 31 males and 13 females with a median age of 39 years (range, 15 to 82 years). 27 patients (61.4%) were stage III/IV, 28(63.6%) with B symptoms, 12(27.3%) ECOG ≥ 2, 18 (40.9%) IPI score ≥ 3, and 48.8% patients had elevated serum lactate dehydrogenase. The common primary sites were skin (21/44, 47.2%) and intestinal tract (11/44, 25.0%). All the 44 patients received systemic chemotherapy. After a median follow-up of 13.5 months (range, 0.3-121.0 months), 32 patients died, and the median overall survival (OS) was 16 months with 1-year OS rate as 54.1%. CR rate of the 26 patients received CHOP or CHOPE regimens as the first line chemotherapy was 19.2% (5/26). Then L-asparaginase (L-ASP)- based regimens were used for salvage treatment, with CR rate of 47.7% and the median OS of 13 months. CR rate of the other 18 patients received L-ASP-based regimens in the firstline therapy was 55.6% (10/18) with the median OS of 16 months. Using L-ASP in firstline treatment obviously improved CR rate (P=0.015), but did not affect OS (P=0.774).</p><p><b>CONCLUSION</b>Although L-ASP improved the efficacy of NUAT-NKTCL, but the prognosis remained dismal. Thus, more effective treatment strategies are required for NUAT-NKTCL.</p>

Prognostic value of 18F-FDG PET-CT in Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine the predictive value of interim and end-of-treatment ¹⁸F-FDG PET-CT after first-line treatment in patients with Hodgkin lymphoma (HL).</p><p><b>METHODS</b>The clinical data of 50 newly diagnosed HL patients were retrospectively analyzed. Baseline, interim and end-of-treatment PET-CT were performed, and then imaging results were analyzed for the survival of patients via software SPSS 13.0.</p><p><b>RESULTS</b>Fifty patients received first-line treatment with ABVD (doxorubicin + bleomycin + vincristine + dacarbazine) or BEACOPP (bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine+ prednisone) regimen. Interim PET-CT of 35 patients were performed after 2-4 cycles of treatment, 46 patients received PET-CT scans at the end of treatment. After a median follow-up of 29.4 months (12.2-52.4 months), the 3-year progression-free survival (PFS) rates were 100% and 70% for the interim PET-CT negative (n=25) and positive (n=10) patients, respectively (P=0.004). The 3-year PFS rates were 100% and 60% for the post-treatment PET-CT negative (n=36) and positive (n=10) patients, respectively (P<0.01).</p><p><b>CONCLUSION</b>Interim and end-of-treatment PET-CT were correlated with 3-year PFS rates for HL patients. They may play an important role in predicting the outcome of HL. The relationship with OS can not be determined because of the short follow-up time.</p>

Analysis of clinical features and prognosis of 98 patients with mantle cell lymphoma / 中国肿瘤临床

Objective:To study the clinical features, therapeutic effects, survival time, and prognosis of patents with mantle cell lymphoma (MCL). Methods:Clinical data of 98 MCL patients admitted from January 2005 to December 2013 were retrospectively an-alyzed. Results:The median age was 61 years old, and the male-to-female ratio was 2.9∶1. Among these cases, 85 (86.8%) were in Ann Arbor stageⅢ-Ⅳ, 46 (46.9%) had bone marrow involvement, 25 (25.5%) had digestive tract involvement, and 53 chose R-CHOP as first-line treatment. The expected 3-year overall survival (OS) of these patients was only 61.4%. A total of 14 cases were treated with R-CHOP followed by ASCT. The expected 5-year OS was 92.3%, and the OS of the ASCT group was significantly higher than that of the R-CHOP group (75.5 months vs. 43.6 months, P=0.039). Elevated ESR,>60 years old, increased LDH level, B symptoms, and Ki-67≥25% were poor prognostic factors. Conclusion: Most patients with MCL were elder adults with bone marrow involvement. R-CHOP followed by ASCT had better clinical efficacy than conventional chemotherapy in the treatment of MCL.

Research progress of chimeric antigen receptor-modified T cell in B cell lymphoma / 白血病·淋巴瘤

The prognosis of B cell lymphoma has been significantly improved in the rituximab era,but there are also patients who are refractory or relapsed after rituximab-containing treatment.Chimeric antigen receptor T (CAR T) cell is a kind of T cell which is genetically modified to target specific antigen expressed on the lymphoma cell surface.The response rate of CAR T cell in relapsed or refractory B cell lymphoma is inspiring.Anti-CD19 CAR T cell is the most popular cell being tested in clinical studies.This article discussed the present situation of CAR T cell in B cell lymphoma,including the efficacy,toxicity,side effects and open questions existing in this treatment.

Autoimmunity and lymphoma / 白血病·淋巴瘤

The association between autoimmunity and lymphoma is bidirectional: patients with autoimmune disorders have an increased risk of developing malignant lymphoma, and autoimmune symptoms occur in the context of malignant lymphoma much more often. The epidemic features, clinical characteristics,and biologic mechanisms that underlie this association have been investigated in many studies, and this review is focused on recent progresses in this area.

Efficacy and safety of modified baseline BEACOPP regimen in the treatment of advanced Hodgkin's lymphoma / 肿瘤

Objective:To investigate the safety and efficacy of a modified baseline BEACOPP regimen(bleomycin+etoposide+adriamycin+cyclophosphamide+vincristine+ procarbazine hydrochloride+ prednisone) in the treatment of advanced Hodgkin 's lymphoma (HL). Methods:From March 2006 to September 2008, 22 previously untreated patients with stages Ⅱ(bulky), Ⅲ and Ⅳ HL were treated with a modified baseline BEACOPP regimen. Each patient was scheduled to receive 6 to 8 cycles of BEACOPP with consolidation radiotherapy to bulky (≥5 cm) or residual disease.Results:There were 11 males and 11 females with a median age of 28 years (15 to 61 years old). Twelve patients (54.5%) had nodular sclerosis HL, and 10(45.5%) had mixed cellularity HL. There were 4 patients in stageⅡ, 7 in stage Ⅲ and 11 in stage Ⅳ. Sixteen patients (72.7%) achieved a complete remission (CR) and 5 patients (22.7%) had partial remission (PR). The total effective rate (CR+PR) was 95.5%. Among all kinds of clinical factors International Prognostic Score (IPS) had significant effect on CR rate (P=0.011). The 1-, 2- and 3-year total survival rates were the same (95.5%); the 1-, 2- and 3-year progression-free survival (PFS) rates were 72.7%, 53.1% and 53.1%, respectively;the 1-, 2- and 3-year disease-free survival rates were 85.9%, 76.4% and 76.4%,respectively. Univariate analysis showed that the gender, IPS and whether achieving CR had significant effects on PFS (P<0.05). The main toxic effects were bone marrow depression and liver injury. Three patients (13.6%) had grade Ⅲ drug-induced lung injury. No treatment-related death was observed.Conclusion:The modified baseline BEACOPP regimen was effective and safe for treatment of newly diagnosed patients with advanced HL.