Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health. It has been hypothesized that chemotherapies, similarly to environmental chemicals, may alter the spermatogenic epigenome. Here, we report the genomic and epigenomic profiling of the sperm DNA from a 31-year-old Hodgkin lymphoma patient who faced recurrent spontaneous miscarriages in his couple 11-26 months after receiving chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). In order to capture the potential deleterious impact of the ABVD treatment on mutational and methylation changes, we compared sperm DNA before and 26 months after chemotherapy with whole-genome sequencing (WGS) and reduced representation bisulfite sequencing (RRBS). The WGS analysis identified 403 variants following ABVD treatment, including 28 linked to genes crucial for embryogenesis. However, none were found in coding regions, indicating no impact of chemotherapy on protein function. The RRBS analysis identified 99 high-quality differentially methylated regions (hqDMRs) for which methylation status changed upon chemotherapy. Those hqDRMs were associated with 87 differentially methylated genes, among which 14 are known to be important or expressed during embryo development. While no variants were detected in coding regions, promoter regions of several genes potentially important for embryo development contained variants or displayed an altered methylated status. These might in turn modify the corresponding gene expression and thus affect their function during key stages of embryogenesis, leading to potential developmental disorders or miscarriages.
Humans ; Male ; Hodgkin Disease/drug therapy* ; Adult ; DNA Methylation/drug effects* ; Bleomycin/therapeutic use* ; Spermatozoa/metabolism* ; Vinblastine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Abortion, Habitual/genetics* ; Doxorubicin/therapeutic use* ; Dacarbazine/therapeutic use* ; Female ; Pregnancy

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bleomycin/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Dacarbazine/therapeutic use* ; Doxorubicin/therapeutic use* ; Etoposide/therapeutic use* ; Hodgkin Disease/drug therapy* ; Humans ; Necrosis/drug therapy* ; Prednisone/therapeutic use* ; Prognosis ; Retrospective Studies ; Sclerosis/drug therapy* ; Vinblastine/therapeutic use* ; Vincristine/therapeutic use*

To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.
Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Cytarabine ; administration & dosage ; Dexamethasone ; administration & dosage ; Humans ; Induction Chemotherapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; mortality ; Neoplasm Recurrence, Local ; drug therapy ; mortality ; Retrospective Studies ; Salvage Therapy ; methods ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vinorelbine

BACKGROUNDThe aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).

METHODSPertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.

RESULTSTwelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m 2 , combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05-1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30-0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m 2 , no significant differences in efficiency (RR = 1.11, 95% CI [0.87-1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71-1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia.

CONCLUSIONSAidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; psychology ; Cisplatin ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Injections ; Lung Neoplasms ; drug therapy ; psychology ; Publication Bias ; Quality of Life ; Vinblastine ; administration & dosage ; analogs & derivatives

OBJECTIVETo characterize the clinical features of desmoid tumor, assess the efficacy of conservative chemotherapy for inoperable desmoid tumor and analyze the prognostic factors.

METHODSFrom August 2009 to December 2013, 52 patients with inoperable desmoid tumor were treated in our department and received chemotherapy with vinorelbine combined with low-dose methotrexate. The clinical data of the patients were analyzed retrospectively.

RESULTSThe patients studied included 22 male and 30 female patients with the age of disease onset ranging from 2 to 46 years (mean 18.7 years). The lesions occurred most frequently in the lower limbs (36.5%, 19/52) and the tumor size ranged from 2.7 to 37 cm (mean 9.5 cm). The patients were followed up for a median of 29 months (7 to 64 months). The chemotherapy lasted for 4 to 30 months (median 12 months). After completion of the chemotherapy, 1 patient had a complete response (CR), 18 showed partial responses (PR), 27 cases had stable disease (SD), and 6 had progressive disease (PD), with an overall response rate (ORR) of 88.5%. The progression-free survival (PFS) time of the patients ranged from 4 to 63 months (median 26.5 months) with a 2-year PFS rate of 76.7% and 5-year PFS rate of 41.9%. A longer chemotherapy duration (over 12 months) was associated with a more favorable prognosis. No significant differences in PFS were found between the patients stratified by gender, age of disease onset, age when receiving chemotherapy, tumor site, or tumor size.

CONCLUSIONFor recurrent, inoperable and progressive desmoid tumor, long enough cycles of vinorelbine combined with low-dose methotrexate can be an effective and safe option for tumor control.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Fibromatosis, Aggressive ; drug therapy ; Humans ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Middle Aged ; Prognosis ; Retrospective Studies ; Vinblastine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficacy of Chinese medicine (CM) combined adjuvant chemotherapy in postponing relapse and metastasis of radical resected Ib-IIIa stage non-small cell lung cancer (NSCLC) patients, and to explore its effect in improving their quality of life (QOL) and clinical symptoms.

METHODSWe designed a cohort study of 336 radical resected Ib-IIIa NSCLC patients by analyzing disease free survival (DFS) using Log-rank test. They were randomly assigned to the control group (155 cases, treated by adjuvant chemotherapy group) and the test group (181 cases, treated by adjuvant chemotherapy combined CM). By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases). QOL scores (using EORTC QLQ-LC43 questionnaire) and TCM symptoms scores were compared between the two groups before chemotherapy, peri-chemotherapy (one day before the 2nd course of chemotherapy) , and after chemotherapy (20 days after ending the 4th course of chemotherapy).

RESULTS(1) The median DFS was longer in the test group than in the control group, but with no statistical difference between the two groups (42.73 months vs 35.57 months , P = 0.179). In the subgroup analysis, there was statistical difference in IIIa stage DFS. The median IIIa stage DFS of was longer in the test group than in the control group with statistical difference (27.87 months vs 19. 93 months, P = 0.047). (2) In the control study, repeated measured data indicated there was significant difference in physical functions between the two groups (P < 0.05). Total scores for health states decreased more in the test group than in the control group, but with no statistical difference (P > 0.05). Scores for constipation and CM syndrome scores were higher in the test group than in the control group (P < 0.05).

CONCLUSIONSCM had advantages in postponing DFS of radical resected NSCLC patients, especially in IIIa stage. CM could improve their QOL and clinical symptoms during adjuvant chemotherapy.

Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Chemotherapy, Adjuvant ; Cisplatin ; therapeutic use ; Cohort Studies ; Disease-Free Survival ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Lung Neoplasms ; Quality of Life ; Vinblastine ; analogs & derivatives ; therapeutic use

OBJECTIVETo assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.

METHODSClinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).

RESULTSAfter 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.

CONCLUSIONSNVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.

Anthracyclines ; therapeutic use ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bridged-Ring Compounds ; therapeutic use ; Capecitabine ; administration & dosage ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Humans ; Neutropenia ; chemically induced ; Retrospective Studies ; Taxoids ; therapeutic use ; Triple Negative Breast Neoplasms ; drug therapy ; pathology ; Vinblastine ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVEThe aim of this study was to investigate the effectiveness of treatment, survival and prognostic factors in Chinese patients with Hodgkin lymphoma.

METHODSA total of previously untreated 415 patients with histologically confirmed Hodgkin lymphoma admitted in the Cancer Hospital, Chinese Academy of Medical Sciences from February 1999 to February 2011 were included in this study. Their short-term and long-term survivals, as well as prognostic factors were analyzed.

RESULTSFor the whole group, 371 cases (89.4%) had complete remission (CR), 33 cases (8.0%) had partial remission (PR) and 11 cases (2.7%) experienced disease progression. The CR rates for stage I, II, III and IV patients were 96.6% (56/58), 92.0% (219/238), 83.6% (51/61) and 77.6% (45/58), respectively (P < 0.001). The 5-year disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) were 90.6%, 84.1% and 92.5%. The stage I-II patients were significantly better than stage III-IV patients in terms of 5-year DFS rate (94.5% vs. 79.2%, P < 0.001), 5-year PFS rate (91.2% vs. 66.4%, P < 0.001) and 5-year OS rate (97.0% vs. 81.5%, P < 0.001). For stage I-II patients, combined modality therapy was related to better DFS, PFS and OS as compared with radiotherapy alone, and was associated with a better PFS compared with chemotherapy alone. There was a trend that consolidative radiotherapy could improve the long-term survival for stage III-IV patients who achieved disease remission after chemotherapy. What's more, consolidative radiotherapy could significantly improve PFS for those stage II-IV patients who achieved PR after chemotherapy. Multivariate analysis showed that clinical stage and pathological type were independent prognostic factors for the 5-year DFS rate (both P < 0.05), and the stage, elevated serum β2-microglobulin and none-ABVD/BEACOP chemotherapy regimen were independent prognostic factors for 5-year PFS rate and 5-year overall survival rate (P < 0.05 for all).

CONCLUSIONSPatients with HL treated in China have a good prognosis. Combined modality therapy is the preferred treatment for stage I-II patients. Consolidative radiotherapy is recommended to those of stage III-IV patients who experienced PR after chemotherapy. Stage, serum β2-microglobulin and first-line chemotherapy regimen significantly affect the prognosis for patients with Hodgkin lymphoma.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Bleomycin ; China ; Combined Modality Therapy ; mortality ; Dacarbazine ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Hodgkin Disease ; mortality ; pathology ; therapy ; Humans ; Multivariate Analysis ; Prognosis ; Radiotherapy, Adjuvant ; mortality ; Remission Induction ; Survival Rate ; Treatment Outcome ; Vinblastine ; beta 2-Microglobulin ; blood

OBJECTIVETo investigate the efficacy and safety of Rituximab combined with second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.

METHODSSeven patients with relapsed and refractory Hodgkin lymphoma were treated with Rituximab combined with second line regimen. Among them, two patients were treated with R-GDP (E) [rituximab, gemcitabine, cisplatin, dexamethasone (etoposide)] regimen, another two patients with R-IGVP (rituximab, ifosfamide, gemcitabine, vinorelbine, prednisone)regimen, and the left three patients with R-BEACOPP (rituximab, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)regimen. The efficacy and safety were evaluated during and after chemotherapy.

RESULTSThere're three male and four female patients, whose median age was 21 years (range 12-36 years) old. One patient was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and the other six patients as classical HL (four nodular sclerosis HL, one lymphocyte-rich classical HL and one hmixed cellularity HL). The median cycles of salvage therapy were 4(1-4), and the median follow-up was 29 months (24-58 months). Among these 7 patients, the complete remission was observed in 4 patients, stable disease in 2 patients, but one patient died during salvage therapy. The two-year survival rates were 85.7% and the major toxic effects were bone marrow suppression.

CONCLUSIONThese results indicate that the Rituximab combined with second line regimen is an effective therapy for relapsed and refractory Hodgkin lymphoma.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Child ; Cisplatin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Dexamethasone ; therapeutic use ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Female ; Hodgkin Disease ; drug therapy ; Humans ; Male ; Neoplasm Recurrence, Local ; Prednisone ; therapeutic use ; Procarbazine ; therapeutic use ; Remission Induction ; Rituximab ; therapeutic use ; Salvage Therapy ; Vinblastine ; analogs & derivatives ; Vincristine ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of patients with HER-2-positive advanced breast cancer.

METHODS132 patients with advanced HER-2-positive breast cancer were treated with trastuzumab plus different regimens. The clinical characteristics, efficacy and toxicity of the 132 patients were retrospectively analyzed.

RESULTSFive patients had complete response (CR), 61 patients had partial response (PR), 39 patients had stable disease (SD), and 27 patients had progressive disease (PD). The objective response rate was 50.0% and the disease control rate was 79.5%. The median progression-free survival was 9.3 months. The median overall survival time was 46.2 months. The 1-, 2-, 5- year survival rates were 98.3%, 81.9% and 40.2%, respectively. Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy (51.2% vs. 33.3%). The number of metastatic sites, efficacy, different previous treatment lines were independent prognostic factors of PFS (P = 0.002, P < 0.0001 and P < 0.0001, respectively). Visceral metastases, pathological grade, and PFS were independent prognostic factors of OS (P = 0.041, P = 0.001, P = 0.025, P < 0.001, P < 0.0001 and P < 0.0001, respectively). Regarding the toxicities, one case discontinued treatment due to the decrease of left ventricular ejection fraction to 47%, two cases had heartbeat tachycardia, 6 cases had palpitation, 17 cases had a fever during first input trastuzumab. No other serious cardiac toxicity was observed. The most common toxicities were chemotherapy-related hematological and non-hematological toxicities.

CONCLUSIONSTrastuzumab combined with chemotherapy is superior to trastuzumab monotherapy. Patients may get benefits for early use of trastuzumab. Trastuzumab plus chemotherapy is effective and well tolerated in patients with advanced HER-2 positive breast cancer. No heart failure occurred in this series of patients, and cardiac safety seems better than that in Caucasians because of younger age at the onset in Chinese advanced breast cancer patients.

Adult ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Disease Progression ; Disease-Free Survival ; Female ; Fever ; chemically induced ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neutropenia ; chemically induced ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vomiting ; chemically induced