Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study.

The phase III GALLIUM trial assessed the safety and efficacy of obinutuzumab-based versus rituximab-based immunochemotherapy in patients with previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL). At the primary analysis, the trial met its primary end point, demonstrating improvement in investigator-assessed progression-free survival (PFS) with obinutuzumab-based versus rituximab-based immunochemotherapy in patients with FL. We report the results of the final analysis in the FL population, with an additional exploratory analysis in the MZL subgroup. Overall, 1202 patients with FL were randomized 1:1 to obinutuzumab- or rituximab-based immunochemotherapy followed by maintenance with the same antibody for up to 2 years. After a median 7.9 (range, 0.0-9.8) years of follow-up, PFS remained improved with obinutuzumab- versus rituximab-based immunochemotherapy, with 7-year PFS rates of 63.4% versus 55.7% (P = 0.006). Time-to-next antilymphoma treatment was also improved (74.1% versus 65.4% of patients had not started their next antilymphoma treatment at 7 y; P = 0.001). Overall survival was similar between the arms (88.5% versus 87.2%; P = 0.36). Irrespective of the treatment received, PFS and OS were higher in patients with a complete molecular response (CMR) versus those with no CMR (P < 0.001). Serious adverse events were reported in 48.9% and 43.4% of patients in the obinutuzumab and rituximab arms, respectively; there was no difference in the rate of fatal adverse events (4.4% and 4.5%, respectively). No new safety signals were reported. These data demonstrate the long-term benefit of obinutuzumab-based immunochemotherapy and confirm its role as a standard-of-care for the first-line treatment of advanced-stage FL, taking into account patient characteristics and safety considerations.

IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B-cell lymphoma.

PURPOSE: Large B-cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. METHODS: The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. RESULTS: Twenty-one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium-sized blastoid cytology, germinal center B-cell-like, and CD5+ phenotype, compared with IRF4- ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4- ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. CONCLUSION: Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Cell-of-Origin Subtyping of Diffuse Large B-Cell Lymphoma by Using a qPCR-based Gene Expression Assay on Formalin-Fixed Paraffin-Embedded Tissues.

The well-established cell-of-origin (COO) algorithm categorizes diffuse large B-cell lymphoma (DLBCL) into activated B-cell-like (ABC) and germinal center B-cell-like (GCB) subgroups through gene expression profiling. We aimed to develop and validate a qPCR-based gene expression assay to determine the COO subgroups of DLBCL with formalin-fixed paraffin-embedded (FFPE) tissue. We first established a DLBCL transcriptome database of 1,016 samples retrieved from three published datasets (GSE10846, GSE22470, and GSE31312). With this database, we identified a qPCR-based 32-gene expression signature (DLBCL-COO assay) that is significantly associated with the COO subgroups. The DLBCL-COO assay was further validated in a cohort of 160 Chinese DLBCL patients. Biopsy samples from DLBCL patients with paired FFPE and fresh frozen tissue were collected to assign COO subtypes based on the immunohistochemistry (IHC) algorithm (Han's algorithm), DLBCL-COO assay, and global gene expression profiling with RNA-seq. For 111 paired FFPE and fresh DLBCL samples, the concordance between the IHC, qPCR, and RNA-seq methods was 77.5% and 91.9%, respectively. The DLBCL-COO assay demonstrated a significantly superior concordance of COO determination with the "gold standard" RNA-seq compared with the IHC assignment with Han's algorithm (P = 0.005). Furthermore, the overall survival of GCB patients defined by the DLBCL-COO assay was significantly superior to that of ABC patients (P = 0.023). This effect was not seen when the tumors were classified by the IHC algorithm. The DLBCL-COO assay provides flexibility and accuracy in DLBCL subtype characterization. These findings demonstrated that the DLBCL-COO assay might serve as a useful tool for guiding prognostic and therapeutic options for DLBCL patients.

Prognostic Significance of LDH Ratio in Serum/Cerebral Spinal Fluid of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma.

OBJECTIVE: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is relatively rare, and risk factors of this disease are still not well understood. This study aims to identify clinical features and prognostic factors of PT-DLBCL patients. METHODS: Thirty-two patients were included in this retrospective study who were diagnosed as PT-DLBCL and treated in Fudan University Shanghai Cancer Center between November 2010 and May 2018. The demographic details, clinico-pathological characteristics of the patients were summarized, and the impact on progression-free survival (PFS) and overall survival (OS) was analyzed. RESULTS: The median age of the patients was 57 (range 36-76) years old. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 4-6 cycles and central nervous system (CNS) prophylaxis, with a CR rate 87.5% and an ORR 96.9%. Nineteen patients continued prophylactic contralateral testis radiation therapy (PCTRT) in our hospital. The 3-year PFS and OS rates were 79% and 92%, respectively. None of the 19 patients who received PCTRT experienced local recurrence. All three patients who suffered from CNS relapse were germinal center B-cell subtype. Kaplan-Meier analyses showed that PT-DLBCL patients with late-stage (Stage IV) (P =0.022), higher IPI score (IPI≥ 2) (P =0.017), B symptoms (P =0.004), and elevated LDH level (P =0.03) had a shorter PFS. More importantly, we found that patients with the ratio of the LDH level in serum to that in CSF ≥ 6.5 suffered from a worse PFS (P =0.028). CONCLUSION: Our work revealed that staging IV, IPI score ≥2, having B symptoms and elevated LDH level were risk factors for PT-DLBCL patients. Significantly, the PT-DLBCL patients with a high ratio of LDH level in serum to that in CSF were indicated to have a worse PFS.

The size and depth of lesions measured by endoscopic ultrasonography are novel prognostic factors of primary gastric diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma is one of the predominant histological subtypes of primary gastric lymphomas. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood. We analyzed 73 primary gastric diffuse large B cell lymphoma patients retrospectively, and found that patients characterized by late stage, multiple localization, B symptoms, lower serum albumin level and elevated LDH level had a shorter overall survival through Univariate Cox regression analysis. Multivariate Cox regression analysis demonstrated that ALB ≤ 35g/L, staging ≥ IIE and multiple sites localization were independent adverse prognostic factors. Significantly, in 35 patients who received endoscopy at diagnosis, Kaplan-Meier analyses indicated that patients with large (≥3 cm) and deep lesions (≥11 mm) had an inferior OS (p = .01 and .039). These findings implicated that tumor size and depth are two indicators of prognosis under ultrasonography. Further randomized studies with large number of cases are needed.

Extranodal natural killer/T-cell lymphoma involving the gastrointestinal tract: analysis of clinical features and outcomes from the Asia Lymphoma Study Group.

BACKGROUND: The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract. PATIENTS AND METHODS: Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries. RESULTS: The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 - 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone. CONCLUSION: Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.

Hepatitis B virus reactivation in B-cell lymphoma patients treated with rituximab: analysis from the Asia Lymphoma Study Group.

BACKGROUND: Hepatitis B virus (HBV) reactivation is increasing, as rituximab has become widely used for B-cell lymphoma. Thus, prevention and management of HBV reactivation are important in HBV-endemic areas. METHODS: Hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-positive patients and HBsAg-negative/HBV core antibody (HBcAb)-positive patients who received rituximab-containing chemotherapy was investigated by the Asia Lymphoma Study Group via retrospective (n=340), and the results were compared to cross-sectional analysis with patients who were prospectively monitored in a single institute (n=127). The goal of the study was to define the frequency of HBV reactivation and the efficacy of antiviral prophylaxis. RESULTS: HBV reactivation was found in 27.8% of HBsAg-positive patients (45/162) in the retrospective analysis, being significantly less frequent in patients receiving antiviral prophylaxis than those not (22.9%, 32/140 versus 59.1%, 13/22; p<0.001). Lamivudine was most commonly used (96/162, 59.3%), but more than 20% of HBsAg-positive patients showed breakthrough HBV reactivation. In the cross-sectional analysis, a reduced rate of HBV reactivation occurred for entecavir as compared with lamivudine prophylaxis (6.3% versus 39.3%; p<0.05). HBV DNA monitoring of HBsAg-negative/HBcAb-positive patients in the cross-sectional analysis showed HBV reactivation in only 2.4% of cases. CONCLUSIONS: This is the largest study of HBV reactivation in patients receiving rituximab-containing chemotherapy to date, and we defined the probability of HBV reactivation in an HBV-endemic region.

Lymphotoxin alpha (LTA) polymorphism is associated with prognosis of non-Hodgkin's lymphoma in a Chinese population.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) has been widely reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the survival and prognosis of NHL patients. To evaluate the role of such genetic variations in prognosis of NHL, we conducted this study in a Chinese population. METHODS: We used the TaqMan assay to genotype six single nucleotide polymorphisms (SNPs) (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T) for 215 NHL cases. Kaplan-Meier analysis was performed to compare progression free survival among two common genotypes. Cox proportional hazard models were used to identify independent risk factors. RESULTS: We observed that LTA rs1800683G>A was significantly associated with risk of progression or relapse in NHL patients (HR = 1.63, 95%CI = 1.06-2.51; P = 0.028), particularly in Diffuse large B cell lymphoma (DLBCL) cases (HR = 1.50, 95%CI = 1.10-2.04, P = 0.01). Both univariate and multivariate Cox regression analysis showed that in DLBCL patients, Ann Arbor stage III/IV, elevated LDH level before treatment and LTA rs1800683 AA genotype carrier were independent risk factors for progression or relapse. While in NK/T cell lymphoma, Ann Arbor stage III/IV and elevated ß2-MG level before treatment indicated poorer prognosis. CONCLUSIONS: The polymorphism of LTA rs1800683G>A contributes to NHL prognosis in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.

Tumor necrosis factor-α induced protein 8 polymorphism and risk of non-Hodgkin's lymphoma in a Chinese population: a case-control study.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) has been reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the susceptibility to NHL. To evaluate the role of such genetic variations in risk of NHL, we conducted a case-control study of 514 NHL patients and 557 cancer-free controls in a Chinese population. METHOD: We used the Taqman assay to genotype six potentially functional single nucleotide polymorphisms (SNPs) in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: We observed a significantly increased risk of NHL associated with the TNFAIP8 rs1045241C>T polymorphism (adjusted OR = 3.03; 95% CI = 1.68-5.45 for TT vs. CC and adjusted OR = 2.03; 95% CI = 1.53-2.69 for CT/TT vs. CC). The risk associated with the T allele was more evident in subgroups of 40-60 year-old, non-smokers or light-smokers (less than 25 pack-years), and subjects with normal weight or overweight. Risk for both B and T cell non-Hodgkin's lymphoma was elevated for CT/TT genotypes (adjusted OR = 1.95, 95% CI = 1.41-2.70 for B cell NHL and adjusted OR = 2.22, 95% CI = 1.49-3.30 for T cell NHL), particularly for DLBCL (adjusted OR = 2.01, 95%CI = 1.41-2.85) and FL (adjusted OR = 2.53, 95% CI = 1.17-5.45). These risks were not observed for variant genotypes of other five SNPs compared with their common homozygous genotypes. CONCLUSIONS: The polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.

Oral fludarabine in combination with doxorubicin and dexamethasone as first-line therapy for nodal peripheral T-cell lymphomas: early results of a prospective multicenter study.

PURPOSE: Nodal peripheral T-cell lymphomas (PTCLs) have particularly poor prognoses. Few data enabling establishment of an accepted standard treatment modality for PTCLs are available. We hypothesized that fludarabine-based regimens are tolerable and effective in treatment for nodal PTCLs. Therefore, this study was to analyze the toxicity of, response rate for, and outcome of treatment for nodal PTCLs with oral fludarabine, doxorubicin, and dexamethasone (FAD). METHODS: Patients with PTCLs received FAD every 28 days, consisting of oral fludarabine at 40 mg/m(2) on days 1-3, doxorubicin at 50 mg/m(2) on day 1, and oral dexamethasone at 20 mg/day on days 1-5. Patients who did not exhibit disease progression received at least four courses of treatment. RESULTS: Thirty-one of 35 patients with previously untreated nodal PTCLs enrolled in the study from 2007 to 2008 were evaluable. The incidence of grade 3-4 neutropenia was 55%. Nine patients had to have dose reductions of fludarabine and doxorubicin, none of whom had grade 3 or 4 toxic effects at the lower dose. Five of 31 patients had pneumonitis. No treatment-related mortality occurred. The response rate for the entire patient population was 71%, and the complete remission rate was 48%. The PFS and OS rates at 2 years were 54.2 and 77.1%, respectively. Four patients had died of cancer progression at the time of this analysis. The serum lactate dehydrogenase level had a significant effect on PFS and OS. CONCLUSION: The FAD regimen had encouraging efficacy with an acceptable toxicity profile in patients with nodal PTCLs.

Advanced breast angiosarcoma completely responding to gemcitabine-containing chemotherapy.

BACKGROUND: For patients with anthracycline-resistant metastatic angiosarcoma, there is currently no available standard for second-line therapy, and a need exists for novel effective regimens to improve response rates. CASE REPORT: We report here on a case of a primary angiosarcoma of both breasts in a 34-year-old woman presenting with lung metastases. Upon completion of 3 cycles of the MAID regimen (mesna, adriamycin, ifosfamide, dacarbazine), computed tomography showed disease progression. Subsequently, a second-line chemotherapy was started using the GVP regimen (gemcitabine, vincristine, cisplatin). Complete response of the lung metastases was achieved after 6 cycles of treatment. CONCLUSION: In the absence of an effective therapy among patients with anthracycline-resistant metastatic breast angiosarcoma, a GVP chemotherapy regimen can be performed as a selective option.

A clinical analysis of primary testicular diffuse large B-cell lymphoma in China.

The objective of this study was to analyze the clinical behavior and treatment policy of patients with primary testicular diffuse large B-cell lymphoma by retrospective analysis of 32 patients at our institute. All patients underwent orchidectomy. Anthracycline-based chemotherapy was administered to 27 patients (84·38%), six of whom also received rituximab; prophylactic intrathecal chemotherapy was given to seven patients (21·88%); and eight patients (25%) received prophylactic scrotal radiotherapy. Thirteen patients had relapse, among whom 12 cases were extranodal recurrences. Seven patients had central nervous system involvement, and four patients relapsed in the contralateral testis. The presence of B symptoms, poor Eastern Cooperative Oncology Group performance status, left testicular involvement, central nervous system involvement, and first relapse within 1 year were associated with worse progression-free survival using univariate analysis. Poor Eastern Cooperative Oncology Group performance status, left testicular involvement, and surgery alone were negative prognostic factors for overall survival.

Clinical features and treatment outcomes of 14 cases of primary ovarian non-Hodgkin's lymphoma: a single-center experience.

To analyze the clinical characteristics, results of treatment, and prognostic factors of patients diagnosed as primary ovarian non-Hodgkin's lymphoma (PONHL). Fourteen cases of PONHL treated in Fudan University Cancer Center during a 10-year period were retrospectively reviewed, and the clinical data of the patients were analyzed for correlation between KPS, clinical stage, tumor size, IPI, ovary involvement, treatment and prognosis. The median age was 45 years, and thirteen patients were diagnosed of diffuse large B-cell lymphoma and one patient lymphoblastic lymphoma. Four patients were stage IE, three stage IIE, and seven stage IVE. The median tumor size was 8 cm (range, 4.0-15.0 cm). The median overall survival (OS) of the 14 patients was 23.0 months (range 11.5-71.2 months). Thirty-six percentage of patients with bilateral ovary involvement had a shorter survival time than those with unilateral ovary involvement (median OS: 19.0 vs. 37.2 months, P=0.014). The OS of Stage IVE was worse than stage IE and stage IIE (median OS: 18.75 vs. 37.5 months, P=0.047). Patients with IPI>2 had worse prognosis than those with IPI≤2 (median OS: 19.0 vs. 42.1 months, P=0.03). PONHL patient with larger tumor mass had worse prognosis (median OS: 19.1 vs. 37.2 months, P=0.019). R-CHOP regimens had a tendency to improve the OS but was not shown to be statistically significant (median OS: 22.4 vs. 37.2 months, P=0.436). The management of PONHL should be based on multi-modality treatment including surgery and chemotherapy. The significant prognostic factors of survival are tumor size, Ann Arbor staging, and IPI.

[Clinical analysis of primary gastric diffuse large B-cell lymphoma].

OBJECTIVE: To analyze the clinical features and prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) and to evaluate the staging system and treatment modality of PG-DLBCL. METHODS: The clinicopathological data of 69 patients with PG-DLBCL were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) were the primary endpoints. RESULTS: The EFS rates at 1, 3, and 5 years were 83.8%, 71.1%, and 69.0%, respectively, with a mean EFS of 91.3 months. The 1-, 3-, and 5-year OS rates were 91.3%, 80.3%, and 72.4%, respectively, with a mean OS of 98.8 months. Univariate analysis revealed that either EFS or OS was significantly prolonged by the following factors (P < 0.05): modified Ann Arbor stage I(E) or II(E1) disease; normal lactate dehydrogenase (LDH) level; normal hemoglobin level; normal albumin level; International Prognostic Index (IPI) of 0 or 1; tumor size < 5 cm; and less depth of invasion. While gender, age, B symptoms at presentation, performance status and treatment modality were not significantly associated with the prognosis (P > 0.05). Cox regression model revealed that only modified Ann Arbor stage and albumin level were independent prognostic factors for EFS and OS. CONCLUSION: The most accurate staging system and the exact role of different therapeutic options for PG-DLBCL are still debated. Further randomized prospective studies with a large number of patients are still needed to establish an optimal management for this disease.

[Clinical significance in detection of immunoglobulin heavy chain clonal rearrangement in bone marrow of patients with B cell lymphoma].

OBJECTIVE: To explore the feasibility of semi-nested PCR technique for detection of immunoglobulin heavy chain (IgH) clonal rearrangement in bone marrow of B-cell lymphoma patient and to further evaluate its clinicopathological value. METHODS: Gene clonal rearrangement of IgH was detected by semi-nested PCR using primers of FR2 & FR3A in 105 bone marrow samples of patients with B-cell lymphoma. The PCR detection results were compared with the cytomorphology of bone marrow aspiration biopsy. The correlation between PCR detection results and clinicopathological factors were evaluated. RESULTS: Among 105 cases of B-cell lymphoma, bone marrow involvement was detected by PCR technique in 48 cases (45.7%), while only 22 cases (21.0%) were detected by bone marrow cytological analysis. There was a significant difference between two methods (P < 0.05), and the concordance rate was 71.4%. The incidence of bone marrow involvement at the time of initial diagnosis detected by PCR technique was 30.8% for diffuse large B cell lymphoma (DLBCL), 25.0% for follicular lymphoma (FL), and 100.0% for small lymphocytic lymphoma (SLL), respectively. Bone marrow involvement detected by PCR detection correlated with Ann Arbor stage. Rate of clonal IgH gene rearrangement by PCR in early B-cell lymphoma was lower than that in advanced stage B-cell lymphoma patients (P = 0.02). There was no statistically significant difference in efficacy between patients with positive and negative results detected by PCR (P > 0.05). But difference in complete response (CR) rate (23.3% and 46.3%) had significant difference (P = 0.019). CONCLUSION: Semi-nested PCR analysis may be an effective method for detection of abnormalities in bone marrow in patients with B-cell lymphoma and is superior to cytomorphology. The positive rate in patients with advanced Ann Arbor stage is higher than that in patients with early Ann Arbor stage, and patients with PCR negative result have more chances to achieved CR after treatment.

Chloroxoquinoline in combination with epirubicin, cisplatin and 5-fluorouracil in metastatic gastric cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and tolerability of combination chemotherapy with epirubicin, cisplatin, 5-fluorouracil (ECF regimen), and Chloroxoquinoline in patients with metastatic gastric cancer. METHODOLOGY: Twenty-two patients with histologically confirmed metastatic gastric adenocarcinoma were treated with a combination of epirubicin 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 1), 5-fluorouracil 500 mg/m2 (days 1 to 5), and Chloroxoquinoline 400 mg (days 1 to 21), with the cycle repeated every three weeks. RESULTS: Twenty patients were evaluable for response. One case of (5%) complete response, seven of (35%) partial response, nine (45%) of stable disease, and three (15%) of progressive disease were observed, giving an overall treatment response rate of 40%. Median survival time was 9.4 months, median progression-free survival was 6.1 months, and the 1-year survival rate was 25%. Both hematologic and non-hemotologic toxicities were well tolerated and no treatment-related deaths occurred. In patients who received Chloroxoquinoline maintenance monotherapy after six cycles of the combination regimen, progression-free survival was nine months. CONCLUSION: The combination regimen demonstrated comparable efficacy and acceptable safety profiles in patients with metastatic gastric cancer. Chloroxoquinoline maintenance monotherapy has a tendency to increase progression-free survival.

[Prognosis of primary non-Hodgkin's lymphoma of the breast].

OBJECTIVE: To analyze the clinical characteristics and prognosis of primary non-Hodgkin's lymphoma of the breast (PNHLB). METHODS: The characteristics, treatment methods and outcomes of 45 patients with PNHLB were retrospectively analyzed. Chemotherapy including CHOP and CHOP-like regimens was administered in 43 patients, and monoclonal antibody therapy in 6 patients. Furthermore, 19 patients underwent radiotherapy after chemotherapy. RESULTS: Of these 45 patients, 37 patients had diffuse large B cell lymphoma (DLBCL), patients with T cell or mucosa-associated lymphoid tissue (MALT) lymphoma were 4, respectively. Overall response rate of first-line chemotherapy was 90.7%. Median overall survival (OS) and progression-free survival (PFS) of all patients was 6.82 and 4.25 years, respectively. The results of Cox regression model analysis showed that international prognostic index score (IPI) (RR = 5.682, P = 0.002) and Ann Arbor stage (RR = 1.836, P = 0.040) were negative independent prognostic factors for OS. Central nervous system involvement (RR = 1.107, P = 0.005) was a negative independent prognostic factor for PFS. CONCLUSION: The patients with PNHLB have early occurrence in lifespan. Most pathologic type was DLBCL. IPI and Ann Arbor stage are two independent prognostic factors for survival.

Interstitial pneumonitis during rituximab-containing chemotherapy for non-Hodgkin lymphoma.

Rituximab is widely used for CD20+ non-Hodgkin lymphoma (NHL). The use of rituximab has been uncommonly associated with pulmonary toxicity. We report here a single institution experience on the clinical characteristics, diagnosis, treatment and outcome of rituximab-induced interstitial lung disease. From May 2007 to February 2008, 107 patients with NHL received rituximab-containing chemotherapy. Among them, nine patients were identified who developed interstitial pneumonitis during rituximab-containing chemotherapy. The median cycles of rituximab prior to presentation was two. Most of the patients manifested with high fever, while some had dyspnea or non-productive cough. Pulmonary diffuse interstitial infiltrations were seen on computed tomography scans of all the patients. Treatment consisted of glucocorticoids with a slow taper and antibiotics against atypical pulmonary pathogens. Eight patients responded to glucocorticoid therapy and recovered, whereas one died of secondary infection. Two of the four patients who were retreated with rituximab had recurrence of interstitial pneumonitis. In conclusion, clinicians should be highly alerted of the possibility of interstitial pneumonitis in NHL patients treated with rituximab-containing regimen. Early recognition, timely establishment of diagnosis and prompt treatment with glucocorticoids in combination with empirical antibiotics are essential for a favourable clinical outcome. Retreatment with rituximab and other cytotoxic agents known to cause pulmonary toxicity should be carefully considered for risk benefit ratio.