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1.
Article in English | WPRIM (Western Pacific) | ID: wpr-977405

ABSTRACT

Background/Aims@#We compared the efficacy of the granisetron transdermal system (GTS) with that of ondansetron for controlling chemotherapy-induced nausea and vomiting (CINV) in patients treated with highly emetogenic chemotherapy (HEC). @*Methods@#We randomized a total of 389 patients to groups treated by GTS and ondansetron before HEC. The primary endpoint was the percentage of patients achieving complete response (CR; no retching/vomiting/rescue medication) of CINV from the time of chemotherapy initiation to 24 hours after the last administration of chemotherapy (prespecified non-inferiority margin of 15%). Quality of life (QoL) was also assessed using the Functional Living Index-Emesis (FLIE). @*Results@#The per protocol analysis included 152 (47.80%) and 166 patients (52.20%) in the GTS and ondansetron groups, respectively. In the full analysis set, the most common diagnosis, regimen, and period of chemotherapy were lung cancer (149 patients, 40.27%), cisplatin-based regimen (297 patients, 80.27%), and 1 day chemotherapy (221 patients, 59.73%). The CR rates were 86.84% and 90.36% in the GTS and ondansetron groups, respectively; the treatment difference was −3.52% (95% confidence interval, −10.52 to 3.48) and met the primary endpoint, indicating that GTS was not inferior to ondansetron. Patient satisfaction, assessed on the FLIE, showed significantly higher scores in the GTS group compared to the ondansetron group (mean ± standard deviation, 1,547.38 ± 306.00 and 1,494.07 ± 312.05 mm, respectively; p = 0.0449). @*Conclusions@#GTS provided effective, safe, and well-tolerated control of CINV and improved the QoL in HEC.

2.
Article in English | WPRIM (Western Pacific) | ID: wpr-966490

ABSTRACT

Purpose@#The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. @*Materials and Methods@#We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. @*Results@#The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). @*Conclusion@#Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

3.
Journal of Gastric Cancer ; : 315-327, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1000902

ABSTRACT

Purpose@#Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. @*Materials and Methods@#Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. @*Results@#Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). @*Conclusions@#After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

4.
Article in English | WPRIM (Western Pacific) | ID: wpr-889725

ABSTRACT

Purpose@#Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib. @*Materials and Methods@#Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed. @*Results@#Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%). @*Conclusion@#To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

5.
Article in English | WPRIM (Western Pacific) | ID: wpr-897429

ABSTRACT

Purpose@#Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib. @*Materials and Methods@#Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed. @*Results@#Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%). @*Conclusion@#To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

6.
Article in English | WPRIM (Western Pacific) | ID: wpr-875501

ABSTRACT

Background/Aims@#Colorectal cancer (CRC) rate increases with aging. Aging-related proteins, such as sirtuins (SIRTs) may be a potential therapeutic target in the elderly patients with CRC. The clinical implications of SIRT1 and SIRT2 have not been reported for elderly patients with cancer. The aim of this study was to evaluate the impact of expression of SIRT1 and SIRT2 on clinical outcome in two extreme age groups of patients with CRC. @*Methods@#The expression of SIRT1 and SIRT2 were evaluated in CRC tissues of 101 patients aged ≥ 80 years and 29 patients aged ≤ 40 years by immunohistochemistry. We defined the patients aged ≥ 80 years as the very elderly and patients aged ≤ 40 years as the young patients. Correlations between the expression of these proteins and clinicopathological features were analyzed. @*Results@#The prognosis for the very elderly patients with high expressions of SIRT1 was significantly worse than that for patients showing low expression (median survival, 24.9 months vs. 38.6 months, p = 0.027) whereas high expression of SIRT2 better prognosis (median survival, 37.9 months vs. 17.3 months, p = 0.006). However, the young patients did not show any difference in prognosis according to expression of SIRT1 and SIRT2. In multivariate analysis, high SIRT1 expression retained statistical significance as a poor prognostic factor in the very elderly patients with CRC. @*Conclusions@#The results suggest that high SIRT1 expression could be predictive of a poor outcome for very elderly patients with CRC.

7.
Cancer Research and Treatment ; : 1249-1256, 2019.
Article in English | WPRIM (Western Pacific) | ID: wpr-763155

ABSTRACT

PURPOSE: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. MATERIALS AND METHODS: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). RESULTS: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). CONCLUSION: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.


Subject(s)
Humans , Area Under Curve , Asian People , Drug Therapy , Geriatric Assessment , Mass Screening , Prospective Studies , Sensitivity and Specificity
8.
Article in English | WPRIM (Western Pacific) | ID: wpr-718013

ABSTRACT

BACKGROUND/AIMS: Elderly patients (≥ 80 years) with colorectal cancer (CRC) tend to avoid active treatment at the time of diagnosis despite of recent advances in treatment. The aim of this study was to determine treatment propensity of elderly patients aged ≥ 80 years with CRC in clinical practice and the impact of anticancer treatment on overall survival (OS). METHODS: Medical charts of 152 elderly patients (aged ≥ 80 years) diagnosed with CRC between 1998 and 2012 were retrospectively reviewed. Patients’ clinical characteristics, treatment modalities received, and clinical outcome were analyzed. RESULTS: Their median age was 82 years (range, 80 to 98). Of 152 patients, 148 were assessable for the extent of the disease. Eighty-two of 98 patients with localized disease and 28 of 50 patients with metastatic disease had received surgery or chemotherapy or both. Surgery was performed in 79 of 98 patients with localized disease and 15 of 50 patients with metastatic disease. Chemotherapy was administered in only 24 of 50 patients with metastatic disease. Patients who received anticancer treatment according to disease extent showed significantly longer OS compared to untreated patients (localized disease, 76.2 months vs. 15.4 months, p = 0.000; metastatic disease, 9.9 months vs. 2.6 months, p = 0.001). Along with anticancer treatment, favorable performance status (PS) was associated with longer OS in multivariate analysis of clinical outcome. CONCLUSIONS: Elderly patients aged ≥ 80 years with CRC tended to receive less treatment for metastatic disease. Nevertheless, anticancer treatment in patients with favorable PS was effective in prolonging OS regardless of disease extent.


Subject(s)
Aged , Humans , Colorectal Neoplasms , Colorectal Surgery , Diagnosis , Drug Therapy , Multivariate Analysis , Retrospective Studies
12.
Korean Journal of Medicine ; : 303-307, 2017.
Article in Korean | WPRIM (Western Pacific) | ID: wpr-189027

ABSTRACT

Actinomycosis is a rare chronic suppurative infectious disease caused by Actinomyces spp. Actinomyces are anaerobic Gram-positive bacteria that colonize the mouth, digestive tract, and genital tract. Thoracic actinomycosis is caused by the aspiration of oropharyngeal materials or the spread of cervicofacial infections. Therefore, poor oral hygiene, smoking, and immunodeficiency are risk factors. Actinomycoses are frequently misdiagnosed as anatomical malignancies and thus assessments of the diseases underlying malignancies are often complicated by the presence of actinomycoses. Here, we report a case of mediastinal actinomycosis presenting with clinical and radiological features of metastatic pancreatic cancer. Clinicians should consider the presence of actinomycosis when cancer patients fail to respond to anti-cancer treatments.


Subject(s)
Humans , Actinomyces , Actinomycosis , Colon , Communicable Diseases , Gastrointestinal Tract , Gram-Positive Bacteria , Lymph Nodes , Mouth , Neoplasm Metastasis , Oral Hygiene , Pancreatic Neoplasms , Risk Factors , Smoke , Smoking
13.
Cancer Research and Treatment ; : 1389-1398, 2016.
Article in English | WPRIM (Western Pacific) | ID: wpr-205897

ABSTRACT

PURPOSE: Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. MATERIALS AND METHODS: Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. RESULTS: Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. CONCLUSION: Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.


Subject(s)
Female , Humans , Male , Male , Breast , Breast Neoplasms , Breast Neoplasms, Male , Carcinoma, Ductal , Chemotherapy, Adjuvant , Estrogens , Korea , Mastectomy , Precision Medicine , Prognosis , ErbB Receptors , Retrospective Studies , Tamoxifen , Trastuzumab
14.
Article in English | WPRIM (Western Pacific) | ID: wpr-76675

ABSTRACT

BACKGROUND/AIMS: Among diffuse large B cell lymphoma (DLBCL) patients, determining the appropriate dose and chemotherapy schedule to balance toxicity and efficacy is harder in elderly than in younger patients. Moreover, there are no currently available clinical factors that consistently identify patients who are unfit to receive chemotherapy. Therefore, the clinical characteristics and outcomes of elderly patients with DLBCL and the causes of treatment-related death were investigated in this study. METHODS: The clinical characteristics and outcomes of 44 elderly (> or = 70 years of age) patients diagnosed with DLBCL between January 2005 and June 2013 were evaluated. Variable clinical data along with the response rate, overall survival (OS), and causes of treatment-related death or treatment interruption were investigated. RESULTS: The median OS was 18.6 months, and 19 patients completed curative treatment. The mean average relative dose intensity of adriamycin in patients who completed chemotherapy was 0.617, and of these patients, 16 achieved complete remission. Chemotherapy incompletion, infectious complications, ex tranoda l involvement, high lactate dehydrogenase, poor performance status, and low albumin level at diagnosis were related to a shorter OS. However, multivariate analysis revealed that only infections and chemotherapy incompletion were significantly related to poor prognosis. The most common cause of treatment-related death was infection, and patients who had experienced infectious complications tended to have lower albumin levels than those of patients without such complications. CONCLUSIONS: In the treatment of elderly lymphoma patients, the dose intensity of adriamycin is not as important as it is in young patients. However, in elderly patients, infections are particularly dangerous, especially in patients with low albumin levels.


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Age Factors , Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chi-Square Distribution , Communicable Diseases/blood , Disease Progression , Doxorubicin/administration & dosage , Geriatric Assessment , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/blood , Multivariate Analysis , Proportional Hazards Models , Remission Induction , Republic of Korea , Retrospective Studies , Risk Factors , Serum Albumin/analysis , Time Factors , Treatment Outcome
15.
Article in Korean | WPRIM (Western Pacific) | ID: wpr-49746

ABSTRACT

Chemotherapy induced peripheral neuropathy (CIPN) could debilitate the quality of life in the patients with cancer. According to the severity of CIPN, the modification of dosage of chemotherapeutic agents and switch to other drugs can be unavoidable. Platinum such as cisplatin and oxalipatin, vinka alkaloids, bortezomib, and taxane can cause CIPN. The characteristics and severity of CIPN depends on the dosages, duration of exposure of chemotherapeutic agents, comcomittant illness or other drugs affecting on peripheral nervous system and the methods of assessment for CIPN. The symptoms may last for several months or permanently even after quitting chemotherapy. Typically it distributed bilaterally and starts from the distal part of extremities and is presented progressively in stocking and glove pattern. Sensory nerve is more involved rather than motor nerve and amplitude of sensory nerve conduction is observed in CIPN. Prevention for CIPN is not effective at present. Tricyclic antidepressant including amitriptyline or nortriptyline and gabapentine have been tried in the practice for the management of CIPN despite of the lack of significant evidence through clinical trials. Recently duloxetine has been reported to decrease pain in the patients with CIPN compared with the patients with placebo (p = 0.03).


Subject(s)
Humans , Alkaloids , Amitriptyline , Cisplatin , Drug Therapy , Extremities , Neural Conduction , Nortriptyline , Peripheral Nervous System , Peripheral Nervous System Diseases , Platinum , Quality of Life , Bortezomib , Duloxetine Hydrochloride
16.
Korean Journal of Medicine ; : 353-357, 2015.
Article in Korean | WPRIM (Western Pacific) | ID: wpr-216641

ABSTRACT

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a rare subtype of malignant non-Hodgkin lymphoma, in which 40% of the cases show spontaneous regression without aggressive treatment. Surgery and focal radiation therapy are the primary forms of treatment for this disease; however, if pcALCL is accompanied by multifocal skin lesions, chemotherapy is also common. The prognosis for pcALCL is generally excellent, with a 5-year survival rate of 85-100%. However, pcALCL with extensive limb disease typically has a poor prognosis. Here, we present a case of pcALCL with extensive limb disease that resulted in the patient's death, despite the use of aggressive chemotherapy.


Subject(s)
Drug Therapy , Extremities , Lymphoma , Lymphoma, Non-Hodgkin , Lymphoma, Primary Cutaneous Anaplastic Large Cell , Prognosis , Skin , Survival Rate
17.
Korean Journal of Medicine ; : 224-230, 2015.
Article in Korean | WPRIM (Western Pacific) | ID: wpr-167629

ABSTRACT

Primary esophageal lymphoma is very rare, and most reported cases are histologically mucosa-associated lymphoid tissue lymphoma. Therefore, the principle treatment strategy for primary esophageal lymphoma focuses on local treatments, such as endoscopic mucosal resection or radiation therapy, but systemic chemotherapy plays the central role in the treatment of diffuse large B cell lymphoma (DLBCL). Generally, standard treatment for DLBCL is six or three cycles of R-CHOP chemotherapy followed by involved field radiation therapy according to stage. However, the optimal treatment strategy for primary esophageal DLBCL, and the role of additional radiation is not settled, due to a paucity of cases. Moreover, the clinical characteristics related to the etiology and natural course are also unknown. Here, we present two cases of primary esophageal DLBCL with a literature review.


Subject(s)
Drug Therapy , Esophagus , Lymphoma , Lymphoma, B-Cell , Lymphoma, B-Cell, Marginal Zone , Lymphoma, Large B-Cell, Diffuse
19.
Blood Research ; : 283-285, 2014.
Article in English | WPRIM (Western Pacific) | ID: wpr-75428

ABSTRACT

No abstract available.


Subject(s)
Polycythemia Vera , Renal Artery Obstruction
20.
Korean Journal of Medicine ; : 357-362, 2014.
Article in Korean | WPRIM (Western Pacific) | ID: wpr-63185

ABSTRACT

Rituximab, an anti-CD20 monoclonal antibody, is an effective target agent against the B lymphocytes in B-cell lymphoid malignancies and various lymphoproliferative diseases. Moreover, the toxicity of rituximab is less severe than that of conventional cytotoxic agents, which has promoted the widespread application of rituximab in the treatment of B-cell lymphoma. However, depletion of B lymphocytes by rituximab, which leads to secondary hypogammaglobulinemia, can cause deterioration of humoral immunity. Although immune reconstitution after hematopoietic stem cell transplantation is known to prevent prolonged hypogammaglobulinemia, very few cases of long-standing hypogammaglobulinemia have been reported. We report herein a case of prolonged hypogammaglobulinemia after rituximab-containing chemotherapy and splenectomy in a patient with non-Hodgkin's lymphoma and discuss the clinical significance and pathogenetic mechanism of this phenomenon with a literature review.


Subject(s)
Humans , Agammaglobulinemia , B-Lymphocytes , Cytotoxins , Drug Therapy , Hematopoietic Stem Cell Transplantation , IgG Deficiency , Immunity, Humoral , Lymphoma , Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Splenectomy , Rituximab
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