1.Long term efficacy of COPADM regimen in the treatment of 20 patients with Burkitt lymphoma.
Dan YANG ; Pu WANG ; Jia CHEN ; Cai Xia LI ; Ying ZHANG ; Xiao Chen CHEN ; De Pei WU
Chinese Journal of Hematology 2018;39(8):645-649
Objective: To investigate the long term efficacy of COPADM regimen in the treatment of Burkitt lymphoma (BL). Methods: The clinical data of 39 patients with BL from April 2006 to June 2017 were retrospectively analyzed. According to different chemotherapy regimens, the patients were divided into COPADM group and control group. Results: ①Of 39 BL patients, 26 were male and 13 female. The median age was 30 (11-63) years old, including 25 younger than 40 and 14 older than 40. Among them, 33 patients were in stage Ⅲ-Ⅳ, 13 patients had B symptoms and 25 patients were IPI score≥3. ② Twenty patients treated with COPADM regimen (COPADM group), the 3 year overall survival (OS) and progression-free survival (PFS) were (83.5±2.6)% and (73.2±3.1)%, respectively. Nineteen patients in the control group had a 3-year OS and EFS of (47.4±2.4) % and (42.1±2.4) %, respectively. There were significant differences in OS and EFS between the two groups (all P<0.001). ③Of the 20 patients in COPADM group, 12 were younger patients (age≤40 years), their 3-year OS and EFS were (93.7±3.9)% and (83.3±5.4)%, respectively. The other 8 patients were older than 40 years old, and their 3-year OS and EFS were (48.3±8.5) %, (37.6±6.0) %, respectively. Both OS and EFS in younger patients was significantly better than older patients (P=0.004, P=0.045). ④ There were 24 patients treated with combination of Rituximab, their 3-year OS and EFS were (73.9±9.2)% and (69.9±9.6)%, respectively. The other 15 patients were treated without Rituximab, and their 3-year OS and EFS were (51.3±13.3) % and (38.1±12.9) %, respectively. There were significant differences in OS and EFS between the two groups (P=0.042, P=0.008). Conclusion: COPADM regimen may improve the efficacy of BL. COPADM combined with Rituximab enables BL patients with greater benefit. The prognosis is significantly worse in patients older than 40 years old than in those less than 40 years old.
Adult
;
Antibodies, Monoclonal, Murine-Derived
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Burkitt Lymphoma/drug therapy*
;
Child
;
Cyclophosphamide
;
Disease-Free Survival
;
Doxorubicin
;
Female
;
Humans
;
Male
;
Middle Aged
;
Retrospective Studies
;
Treatment Outcome
;
Vincristine
2.Aidi Injection-Asisted R-CHOP Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma.
Guo-Quan LU ; Xiao-Hong ZHOU ; Hong CHEN ; Jian-Ping TAN
Journal of Experimental Hematology 2016;24(3):733-737
OBJECTIVETo investigaate the clinical efficacy of Aidi injection-asisted R-CHOP chemotherapy for the treatment of diffuse large B-cell lymphoma (DLBCL).
METHODSFifty-one patients diagnosed as DLBCL in our department from February 2005 to September 2015 were randomly divided into 2 groups. Out of them, 26 patients in one group received R-CHOP chemotherapy asisted by Aidi intravenous infection (Aidi+R-CHOP group), 25 patients were in another group received only R-CHOP chemotherapy (R-CHOP group), 3 weeks for one course, to tally continuous 2 courses. The recent therapeutic efficacy, adverse events, quality of life, sIL-2R level and long-term survival rate were compared between 2 groups.
RESULTSThe efficacy of the Aidi+R-CHOP group was significantly higher than that of the R-CHOP group (P<0.05); the incidences of neutropenia and thrombocytopenia were significantly lower than the R-CHOP group (P<0.05); besides, KPS scores were significantly higher than in the R-CHOP group (P<0.05); sIL-2R level in the Aidi+R-CHOP group after treatment was significantly lower than that in the R-CHOP group (P<0.05), however, these data were not statistically different between the two groups before treatment. In addition, 3 and 5-year progression-free survival (PFS) rate in the Aidi+R-CHOP group was significantly higher than that in the R-CHOP group.
CONCLUSIONThe use of Aidi injection-asisted R-CHOP chemotherapy for treating patients with diffuse large B-cell lymphoma can increase the patient's tolerance to chemotherapy, improve their quality of life, also reduce the side-effects of chemotherapy, and the trerapeutic effect is more significant than that of R-CHOP regimen alone, thus improving the overall therapeutic efficacy of patients with diffuse large B-cell lymphoma.
Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Neutropenia ; Prednisone ; therapeutic use ; Quality of Life ; Rituximab ; therapeutic use ; Vincristine ; therapeutic use
3.Rituximab plus Autologous Hemotopoietic Stem Cell Transplantation for The Treatment of CD5 Positive Diffuse Large B Cell Lymphoma with Autoimmune Hemolytic Anemia.
Yi-Qun HUANG ; Rui-Ji ZHENG ; Rong-Juan WU ; Xu-Dong MA
Journal of Experimental Hematology 2016;24(3):722-726
OBJECTIVETo summarize the clinical features and therapy experience of a case of CD5 positive diffuse large B cell lymphoma (CD5+ DLBCL) with autoimmune hemolytic anemia (AIHA).
METHODSA 49-years old patient was investigated. The routine blood examination, bone marrow smear, Coombs test, serological test, chest CT, abdominal MR and immunochemistry etc were performed for this patient; and therapeutic effects of the chemotherapy regimen consisting of rituximab plus autologous hematopoietic stem cell transplantation (auto-HSCT) were observed.
RESULTSThe cervical lymphnode biopsy confirmed CD5+ DLBCL; the severe anemia, reticulocyte increase, Coombs test positive, and erythroid hyperplasia in bone marrow all suggested the occurence of autoimmune hemolytic anemia (AIHA). After plasma exchange, immune suppression using methylprednisolone, blood transfusion, one course of chemotherapy with "R-CHOP-E", the symptoms of AIHA in patient disappeared. After a continuous treatment for 3 courses of "R-CHOP-E", the bone marrow infiltration appeared, which was assessed as "PD", then the treatment was changed to the "R-ESHAP" for 4 courses, the patient was reassessed as "CR". The patient subsequently underwent auto-HSCT, followed up for 6 months, patientis still "CR".
CONCLUSIONThe status of the CD5+ DLBCL patient with AIHA is severe, and the prognosis is poor. The curative effect of the chemotherapy regimen with rituximab plus auto-HSCT for this patien is well.
Anemia, Hemolytic, Autoimmune ; therapy ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD5 Antigens ; metabolism ; Cisplatin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Cytarabine ; therapeutic use ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; therapy ; Methylprednisolone ; therapeutic use ; Middle Aged ; Prednisone ; therapeutic use ; Rituximab ; therapeutic use ; Sentinel Lymph Node Biopsy ; Vincristine ; therapeutic use
4.Rituximab and Dexamethasone Combined with Cyclophosphamide for Treatment of Relapsed and Refractory Immune Thrombocytopenia.
Xiao-Dan HAN ; Jian ZHOU ; Feng-Kuan YU ; Bai-Jun FANG ; Yan-Li ZHANG ; Xu-Dong WEI ; Yong-Ping SONG
Journal of Experimental Hematology 2016;24(1):162-166
OBJECTIVETo evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP).
METHODSTwelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks. The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay (ELISA), and the percentages of Breg, Treg and Th17 cells were detected by flow cytometry before and after treatment. Efficiency was evaluated according to platelet counts, and side effects were observed.
RESULTSSix out of 12 patients reached to complete remission and 4 patients reached to partial remission, with the total response rate 83.33%. The platelet counts [(115.42 ± 76.60) × 10(9)/L] after treatment were significantly higher than that before treatment [(115.42 ± 76.60) × 10(9)/L] (P < 0.001). The ratio of IFN-r/ IL4 after treatment (5.89 ± 2.30) was very significantly lower than that before treatment (7.00 ± 2.73) (P = 0.002). The percentage of Breg cells after treatment [(21.27 ± 4.28)%] were much significantly higher than that before treatment [(15.48 ± 1.67)%] (P < 0.001). The ratio of Treg/Th17 after treatment (3.07 ± 1.50) was significantly higher than that before treatment (0.98 ± 0.45) (P < 0.001). Infusion reaction was observed in 1 patient, secondary hypertension and hyperglycemia were in 1 patient, and pneumonia in 2 patients.
CONCLUSIONRituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractory immune thrombocytopenia patients and they were well tolerated, its mechanism may be related with the balance between T cell sunsets and Treg cells.
Antibodies, Monoclonal, Murine-Derived ; B-Lymphocytes, Regulatory ; cytology ; Cyclophosphamide ; therapeutic use ; Dexamethasone ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Platelet Count ; Prospective Studies ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Remission Induction ; Rituximab ; therapeutic use ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology
5.Evaluation Value of Invasion Area PET-CT Scanning for Chemotherapeutic Efficacy and Prognosis of Patients with Lymphoma.
Jie WANG ; Hua PANG ; Xing-Guo JING ; Dong DUAN ; Lu XU
Journal of Experimental Hematology 2016;24(1):106-109
OBJECTIVETo investigate the evaluation value of invasion area PET-CT scanning for chemotherapeutic efficacy and prognosis of patients with lymphoma.
METHODSA total of 98 newly diagnosed patients with lymphoma received the chemotherapy by R-CHOP protocol, the PET-CT scan of whole body and invasion area was performed after 6 cycle of chemotherapy. The invasion area was determined by PET-CT scan results before chemotherapy. The difference of clinical stage, clinical efficacy, radiation dose and scanning time were compared between PET-CT scanning of whole body and invasion area.
RESULTSThe clinical stages of PET-CT scaning of whole body and invasion area were complete consistent, the consisitent rate of clinical stages from whole body and invasion area PET-CT scaning with Ann Arbor staging was 95.9%(94/98). Whole body PET-CT scan showed that 68 cases achieved CR, 26 cases achieved PR, 1 case achieved SD, 3 cases achieved PD. PET-CT scan of invasion area showed that 68 cases achieved CR, 24 cases achieved PR, 2 cases achieved SD, and 4 cases achieved PD; the PET-CT scan results of the whole body and the invasion area was consistent with CR. In 68 patients with CR, the radiation dose of CT, PET and PET-CT was significantly lower than that of whole body PET-CT, and the scanning time was significantly less than that of whole body PET-CT (P < 0.05).
CONCLUSIONFor clinical efficicacy with CR patients, the scan results of whole body and invasion area PET-CT are consistent, and the PET-CT invasion area can significantly reduce the radiation dose and scanning time; and for PR, SD and PD patients, the whole body PET-CT scan should be performed to evaluation clinical efficiency.
Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Humans ; Lymphoma ; diagnosis ; drug therapy ; Positron-Emission Tomography ; Prednisone ; therapeutic use ; Prognosis ; Tomography, X-Ray Computed ; Vincristine ; therapeutic use
6.Role of frontline autologous stem cell transplantation in young, high-risk diffuse large B-cell lymphoma patients.
Jae Ho YOON ; Jong Wook KIM ; Young Woo JEON ; Sung Eun LEE ; Ki Seong EOM ; Yoo Jin KIM ; Seok LEE ; Hee Je KIM ; Chang Ki MIN ; Jong Wook LEE ; Woo Sung MIN ; Chong Won PARK ; Seok Goo CHO
The Korean Journal of Internal Medicine 2015;30(3):362-371
BACKGROUND/AIMS: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. METHODS: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score > or = 2. From 2006 to 2011, among the 150 DLBCL patients aged < or = 60 years who were treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a complete response (CR) were treated with auto-HSCT. For comparison, we selected 35 well-matched high-risk patients with CR who completed R-CHOP treatment alone. In addition, there were 81 low-risk patients and 11 refractory patients. RESULTS: DLBCL patients with an aaIPI score > or = 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. CONCLUSIONS: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.
Adolescent
;
Adult
;
Age Factors
;
Antibodies, Monoclonal, Murine-Derived/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
;
Biomarkers, Tumor/blood
;
Chemotherapy, Adjuvant
;
Cyclophosphamide/therapeutic use
;
Disease Progression
;
Disease-Free Survival
;
Doxorubicin/therapeutic use
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
L-Lactate Dehydrogenase/blood
;
Lymphoma, Large B-Cell, Diffuse/blood/mortality/pathology/*surgery
;
Male
;
Middle Aged
;
Neoadjuvant Therapy
;
Neoplasm Staging
;
Predictive Value of Tests
;
Prednisone/therapeutic use
;
Proportional Hazards Models
;
Reproducibility of Results
;
Risk Assessment
;
Risk Factors
;
*Stem Cell Transplantation
;
Time Factors
;
Transplantation, Autologous
;
Treatment Outcome
;
Up-Regulation
;
Vincristine/therapeutic use
;
Young Adult
7.The First Case Report of Composite Bone Marrow Involvement by Simultaneously Developed Peripheral T-Cell Lymphoma, Not Otherwise Specified, and Diffuse Large B-Cell Lymphoma.
Hyun Ki KIM ; Chan Jeoung PARK ; Seongsoo JANG ; Young Uk CHO ; Sang Hyuk PARK ; Jene CHOI ; Chan Sik PARK ; Jooryung HUH ; Young Hwa CHUNG ; Jung Hee LEE
Annals of Laboratory Medicine 2015;35(1):152-154
No abstract available.
Antibodies, Monoclonal, Murine-Derived/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
;
B-Cell-Specific Activator Protein/metabolism
;
Bone Marrow/metabolism/*pathology
;
Cyclophosphamide/therapeutic use
;
Doxorubicin/therapeutic use
;
Endoscopy, Digestive System
;
Female
;
Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
;
Genetic Loci
;
Humans
;
Liver/metabolism/pathology
;
Lymphocytes/cytology/immunology
;
Lymphoma, Large B-Cell, Diffuse/complications/*diagnosis/drug therapy
;
Lymphoma, T-Cell, Peripheral/complications/*diagnosis/drug therapy
;
Middle Aged
;
Prednisone/therapeutic use
;
Receptors, Antigen, T-Cell, gamma-delta/genetics
;
Tomography, X-Ray Computed
;
Vincristine/therapeutic use
8.Rituximab treatment strategy for patients with diffuse large B-cell lymphoma after first-line therapy: a systematic review and meta-analysis.
Yuan-Rong REN ; Yong-Dong JIN ; Zhi-Hui ZHANG ; Li LI ; Ping WU
Chinese Medical Journal 2015;128(3):378-383
BACKGROUNDRituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.
METHODSWe performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled.
RESULTSSeven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94), P = 0.02], progression-free survival (PFS) [HR = 0.61, 95% CI (0.52-0.72), P < 0.05], odds ratio (OR) [RR = 1.26, 95% CI (1.07-1.47), P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65) P =0.001].
CONCLUSIONSAfter first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it's not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.
Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Rituximab
9.Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Jung Min HA ; Won SOHN ; Ju Yeon CHO ; Jeung Hui PYO ; Kyu CHOI ; Dong Hyun SINN ; Geum Youn GWAK ; Moon Seok CHOI ; Joon Hyeok LEE ; Kwang Chul KOH ; Seung Woon PAIK ; Byung Chul YOO ; Yong Han PAIK
Clinical and Molecular Hepatology 2015;21(3):232-241
BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology
;
Adult
;
Aged
;
Antibodies, Monoclonal, Murine-Derived/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
;
Antiviral Agents/therapeutic use
;
Cyclophosphamide/therapeutic use
;
DNA, Viral/analysis
;
Doxorubicin/therapeutic use
;
Female
;
Hepatitis B virus/genetics
;
Hepatitis B, Chronic/complications/*diagnosis/drug therapy
;
Hospitalization
;
Humans
;
Liver Transplantation
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Odds Ratio
;
Prednisone/therapeutic use
;
Prognosis
;
Retrospective Studies
;
Severity of Illness Index
;
Vincristine/therapeutic use
;
Young Adult
10.Single Nodular Opacity of Granulomatous Pneumocystis Jirovecii Pneumonia in an Asymptomatic Lymphoma Patient.
Hyun Soo KIM ; Kyung Eun SHIN ; Ju Hie LEE
Korean Journal of Radiology 2015;16(2):440-443
The radiologic findings of a single nodule from Pneumocystis jirovecii pneumonia (PJP) have been rarely reported. We described a case of granulomatous PJP manifesting as a solitary pulmonary nodule with a halo sign in a 69-year-old woman with diffuse large B cell lymphoma during chemotherapy. The radiologic appearance of the patient suggested an infectious lesion such as angioinvasive pulmonary aspergillosis or lymphoma involvement of the lung; however, clinical manifestations were not compatible with the diseases. The nodule was confirmed as granulomatous PJP by video-assisted thoracoscopic surgery biopsy.
Aged
;
Antibodies, Monoclonal, Murine-Derived/adverse effects/therapeutic use
;
Antineoplastic Agents/adverse effects/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
;
Biopsy/methods
;
Cyclophosphamide/adverse effects/therapeutic use
;
Doxorubicin/adverse effects/therapeutic use
;
Female
;
Humans
;
Lymphoma, Large B-Cell, Diffuse/drug therapy/microbiology
;
Pneumocystis jirovecii/pathogenicity
;
Pneumonia, Pneumocystis/*diagnosis/*radiography
;
Positron-Emission Tomography
;
Prednisone/adverse effects/therapeutic use
;
Solitary Pulmonary Nodule/*microbiology
;
Thoracic Surgery, Video-Assisted
;
Tomography, X-Ray Computed
;
Vincristine/adverse effects/therapeutic use

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