Progress of targeted drugs for treatment of diffuse large B-cell lymphoma / 白血病·淋巴瘤

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive lymphoma. The relapsed/refractory DLBCL patients have poor outcomes and DLBCL is still lack of effective treatment standard regimens. How to effectively treat relapsed/refractory DLBCL patients has become a research hotspot, and the current treatment methods include bispecific antibody therapy, chimeric antigen receptor T-cell (CAR-T) therapy, antibody-drug conjugates (ADC) therapy. This paper reviews the progress of targeted drugs/cell treatment for DLBCL at the 64th American Society of Hematology annual meeting.

Application progress of autologous stem cell transplantation in lymphoma treatment / 白血病·淋巴瘤

In recent years, due to the progress of cell-targeted therapy and the presence of a large number of new drugs, the treatment efficacy and survival of many lymphoma patients have improved. As a traditional treatment method, autologous stem cell transplantation (ASCT) still plays an important role in lymphoma treatment. ASCT can be a curable method in some clinical situations. Many clinical studies in recent years have further confirmed the role of ASCT in high-risk aggressive lymphoma and Hodgkin lymphoma. The efficacy of ASCT can be improved by combining antibodies such as brentuximab vedotin, programmed death 1, programmed death ligand 1 or chimeric antigen receptor T cell therapy, and the recurrence risk of ASCT may be decreased.

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.

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>

Advances in the diagnosis and treatment of mantle cell lymphoma / 中国肿瘤临床

Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin's lymphomas (NHLs). MCL comprises distinct subtypes with different pathological characteristics and clinical features. However, MCL remains incurable by intensified first-line regimens con-taining cytarabine and involving consolidation with high-dose therapy and autologous stem cell transplantation. Recently discovered somatic mutations and aberrant intracellular signaling pathways have been demonstrated to play an essential role in the pathogenesis of MCL. The related novel therapeutics, such as Btk inhibitors, PI3K inhibitors, and immune modulators, have exhibited promising ther-apeutic effects on untreated or even relapsed/refractory MCL. The development of an efficient combination therapy is urgently need-ed to improve the survival of MCL patients in the future.

Expression and prognostic value of COX- 2, p16(INK4A) and p53 in patients with classical Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of COX-2, p16(INK4A) and p53 in patients with classic Hodgkin's lymphoma (cHL), and to evaluate their correlation with prognosis.</p><p><b>METHODS</b>The clinical data and samples of 52 cHL cases were collected. Immunohistochemical staining was performed to analyze the proteins level mentioned above and in situ hybridization of EBV encoded RNA (EBER) to clarify the tumor EBV infection state. Correlation between the protein expression and prognosis of patients was analyzed.</p><p><b>RESULTS</b>Of 52 cases, the male and female ratio was 1.6∶1, the age was from 22 to 68 years old. All lesions located primarily in lymph nodes. All samples from 52 cases were stained with COX-2, p16(INK4A) and p53, and the positive expression of COX-2 was found in 28 cases (53.8%）, that of p16(INK4A) in 25 cases (48.1%)and p53 in 42 cases (80.8%）. All patients were divided into two groups according to differences in age (<40 years/ ≥ 40 years), gender (male/female), EBV infection (yes/no), B symptoms (yes/no), and the Ann Arbor staging (Ⅰ-Ⅱ/Ⅲ-Ⅳ), the correlation with COX-2, p16(INK4A) and p53 expression were analyzed, and only p53 expression was correlated with Ann Arbor staging (P=0.027). The statistical analysis of correlations between COX- 2, p16(INK4A) and p53 showed that the expression of COX-2 was strongly correlated with p53 (P=0.008), and p16 (INK4A) was not related to either COX-2 or p53 (P=0.246 and 0.958). Kaplan- Meier univariate OS analysis using SPSS17.0 software showed that only COX-2 expression was an adverse prognostic factor for patients'event free survival (EFS) (P=0.003). Meanwhile COX-2 expression was a unique independent prognostic factor analyzed by COX proportional hazards regression model (HR=0.091, 95% CI 0.017-0.505, P=0.006).</p><p><b>CONCLUSION</b>The expression rate of COX-2, p16 (INK4A) and p53 in the cHL were relatively high; and they were not statistically correlated with tumor EBV infection status; the COX-2 positive group had poor prognosis, but only event free survival time becomes statistically significant shorter. COX proportional hazard regression model was used to analyze the COX-2 expression as a independent adverse prognostic factors for EFS.</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.

Clinical Analysis of 13 Cases of Burkitt Lymphoma and Burkitt-like Lymphoma / 中国肿瘤临床

Objective:To summarize the clinical characteristics of Burkitt lymphoma(BL)and Burkitt-like lymphoma(BLL)and the effect of treatment on 13 cases,and to explore the treatment-related complications and optimal treatment.Methods:Clinical data of 13 BL and BLL patients treated between August 1996 and October 2008 in our hospital were retrospectively analyzed.All of these patients received chemotherapy as the first-line treatment.The efficacy and adverse reactions were evaluated.Results:Of the 13 patients,there were 12 males and 1 female,with a median age of 15 years(ranging from 11 to 62).There were 3 stage Ⅰ cases,2 stage Ⅱ cases,2 stage Ⅲ cases,and 6 stage Ⅳ cases.The advanced stage(stage Ⅲ and Ⅳ)patients accounted for 61.5%(8 cases).CNS was involved in 4 cases and bone marrow was involved in 2 cases at diagnosis.The commonly involved sites included superficial lymph nodes(61.5%),abdominal organs(53.8%),and celiac and retro-pentoneal lymph nodes(38.5%).B symptoms were observed in 7 patients(53.8%).Serum lactate dehydrogenase level was elevated in 8 of 10 cases,while serum udc acid level was elevated in 1 of 10 cases.Eleven patients were diagnosed as BL and 2 patients were diagnosed as BLL.Of the 13 patients,11(84.6%) achieved complete remission(CR)or CR/unconfirmed(CRu),and 1 patient(7.7%) got partial remission(PR).Dudng the follow-up of 8 months(ranging from 5 to 35),6 patients were still alive.The 1-year overall survival,progression-free survival and disease-free survival were 56.98%,32.31% and 39.77%,respectively.Nine patients(69.2%)developed grade Ⅲ or Ⅳ myelosuppression.Conclusion:Intensive short-course chemotherapy is the optimal first-line treatment for BL and BLL.

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.

Diagnosis and treatment of mucosa-associated lymphoid tissue lymphoma / 白血病·淋巴瘤

To describe the epidemiology, etiology, pathological features, clinical manifestation,diagnosis and management, and the role of surgery in mucosa-assoeiated lymphoid tissue (MALT) lymphoma.The relationship between the pathogenesis of gastric MALT lymphoma and helicobacter pylori infection, and its therapeutic principles and follow up study were specially stressed.