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author:("Kim, Won semg")
1.  Clinical outcomes of radiation therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma 
AIM: To evaluate the clinical outcomes of radiation therapy (RT) for early-stage gastric mucosa-associated lymphoid tissue lymphoma (MALToma).
METHODS: The records of 64 patients treated between 1998 and 2011 were analyzed retrospectively. For Helicobacter pylori (H. pylori)-positive patients (n = 31), chemotherapy or H. pylori eradication therapy was the initial treatment. In patients with failure after H. pylori eradication, RT was performed. For H. pylori-negative patients (n = 33), chemotherapy or RT was the first-line treatment. The median RT dose was 36 Gy. The target volume included the entire stomach and the perigastric lymph node area.
RESULTS: All of the patients completed RT without interruption and showed complete remission on endoscopic biopsy after treatment. Over a median follow-up period of 39 mo, the 5-year local control rate was 89%. Salvage therapy was successful in all relapsed patients. Secondary malignancies developed in three patients. The 5-year overall survival rate was 94%. No patient presented symptoms of moderate-to-severe treatment-related toxicities during or after RT.
CONCLUSION: Radiotherapy results in favorable clinical outcomes in patients with early-stage gastric MALToma who experience failure of H. pylori eradication therapy and those who are H. pylori negative.
doi:10.3748/wjg.v19.i36.6062
PMCID: PMC3785628  PMID: 24106407
Gastric mucosa-associated lymphoid tissue lymphoma; Radiation therapy; Treatment response
2.  Clinical characteristics, pathological distribution, and prognostic factors in non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study 
Background/Aims
In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively.
Methods
From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL.
Results
The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age ≥ 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival.
Conclusions
DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age ≥ 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.
doi:10.3904/kjim.2014.29.3.352
PMCID: PMC4028525  PMID: 24851070
Head and neck; Non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; T-cell lymphoma
3.  Clinical features and treatment outcomes in patients with mantle cell lymphoma in Korea: Study by the Consortium for Improving Survival of Lymphoma 
Blood research  2014;49(1):15-21.
Background
We investigated the clinical features and treatment outcomes of patients with mantle cell lymphoma (MCL) in Korea.
Methods
We retrospectively analyzed the clinical characteristics and prognosis of 131 patients diagnosed with MCL between January 2004 and December 2009 at 15 medical centers in Korea; all patients received at least 1 chemotherapeutic regimen for MCL.
Results
The median age for the patients was 63 years (range, 26-78 years), and 77.9% were men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty-two patients (39.7%) were categorized with high- or high-intermediate risk MCL according to the International Prognostic Index (IPI). Eighteen patients (13.7%) were in the high-risk group according to the simplified MCL-IPI (MIPI). The overall incidence of extranodal involvement was 69.5%. The overall incidence of bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%, respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab were used frequently as the first-line treatment (41.2%). With a median follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%. Multivariate analysis showed that the simplified MIPI was significantly associated with OS. However, the use of a rituximab-containing regimen was not associated with OS and EFS.
Conclusion
Similar to results from Western countries, the current study found that simplified MIPI was an important prognostic factor in Korean patients with MCL.
doi:10.5045/br.2014.49.1.15
PMCID: PMC3974951  PMID: 24724062
Mantle cell lymphoma; Epidemiology; Trend; Survival; Chemotherapy; Rituximab
4.  Review of the clinical research conducted by the Consortium for Improving Survival of Lymphoma of the Korean Society of Hematology Lymphoma Working Party 
Blood research  2013;48(3):171-177.
The Consortium for Improving Survival of Lymphoma (CISL) in Korean Society of Hematology Lymphoma Working Party had first meeting in February, 2006 with 10 institutions and 12 members. Now CISL comprised of 64 centers. CISL has concentrated research activity on lymphomas which are relatively frequent in Korea and has tried to give favors for the Korean lymphoma patients. CISL has conducted more than 30 retrospective studies to evaluate Korean peculiar lymphoma subtypes. More than 30 prospective trials have been being performed for diffuse large B-cell lymphoma, marginal zone lymphoma, extra-nodal NK/T-cell lymphoma, and so on. The first prospective trial for advanced marginal zone lymphoma has led to use Rituximab containing chemotherapy with the re-imbursement of health insurance in Korea. The multi-center trials of the CISL with new therapeutic modalities will improve further the survival of lymphoma patients not only quantitatively but also qualitatively.
doi:10.5045/br.2013.48.3.171
PMCID: PMC3786276  PMID: 24086936
Lymphoma; KSH; Lymhoma working party; CISL
5.  Clinical features and survival outcomes of patients with diffuse large B-cell lymphoma: analysis of web-based data from the Korean Lymphoma Working Party Registry 
Blood research  2013;48(2):115-120.
Background
This study aimed to survey the clinical spectrum of diffuse large B-cell lymphoma (DLBCL) in terms of epidemiology, pathologic subtypes, stage, and prognostic index as well as treatment outcomes.
Methods
In 2007-2008, 13 university hospitals evenly distributed in the Korean peninsula contributed to the online registry of DLBCL at www.lymphoma.or.kr and filed a total of 1,665 cases of DLBCL recorded since 1990.
Results
Our analysis showed a higher prevalence of DLBCL in male than in female individuals (M:F=958:707), and extranodal disease was more common than primary nodular disease (53% vs. 47%). Among the 1,544 patients who had been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-CHOP (R-CHOP) therapy with or without radiation, 993 (63.9%) were alive, with 80% free of disease, 417 were dead (26.8%), with 13% free of disease, and 144 (9.3%) were lost to follow-up, with 23% free of disease. Age below 60 years, stage at diagnosis, international prognostic index (IPI) score regardless of age, and addition of rituximab to CHOP therapy in low- and low-intermediate-risk groups according to IPI scores significantly increased survival duration.
Conclusion
The epidemiology, clinical spectrum, and biological behavior of DLBCL in Korea are similar to those observed in Western countries, and the advent of rituximab improved survival.
doi:10.5045/br.2013.48.2.115
PMCID: PMC3698396  PMID: 23826580
Diffuse large B-cell lymphoma; Epidemiology; Survival; Rituximab; CHOP regimen
6.  EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood 
Korean Journal of Pathology  2013;47(2):137-147.
Background
Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality.
Methods
Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed.
Results
STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis.
Conclusions
EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.
doi:10.4132/KoreanJPathol.2013.47.2.137
PMCID: PMC3647126  PMID: 23667373
Epstein-Barr virus infections; Lymphoma, T-cell; Killer cells, natural; Lymphoproliferative disorders; Clonality
7.  Extranodal natural killer/T-cell lymphoma with long-term survival and repeated relapses: does it indicate the presence of indolent subtype? 
The Korean Journal of Hematology  2012;47(3):202-206.
Background
Extranodal natural killer (NK)/T-cell lymphoma is a subtype of lymphoma that is derived from NK cells. It is considered as an aggressive form of non-Hodgkin's lymphoma because of frequent relapses and resistance to treatment. Relapsed NK/T-cell lymphoma often follows a fulminant course that is refractory to conventional chemotherapy treatment.
Methods
Several patients with extranodal NK/T-cell lymphoma showed long-term survival in spite of frequent relapses. Thus, the medical records of patients diagnosed with extranodal NK/T-cell lymphoma from 1995 to 2007 were reviewed and assessed.
Results
Of the 140 cases reviewed, 6 were selected (4.29%). Each of these patients had a minimum of 3 relapses or disease progression during the follow-up period, and their median overall survival was 66 months (range, 42-89 months). They were grouped according to the atypical clinical behavior observed: (1) repeated relapses or progression (≥3 times) during follow-up; and (2) long-term survival of more than 40 months, as the longest overall survival median was previously considered at approximately 40 months. The clinicopathological and laboratory characteristics of these patients were similar to those of other extranodal NK/T-cell lymphoma patients. However, 5 of the studied cases involved relatively lower expression of the proliferation-related antigen Ki-67 (<40-50%), indicating less proliferative activity. Clinically, they showed delayed relapse for at least 20 months after the initial complete remission.
Conclusion
Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.
doi:10.5045/kjh.2012.47.3.202
PMCID: PMC3464337  PMID: 23071475
Extranodal NK/T-cell lymphoma; Relapse; Survival; Indolent
9.  A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas 
Background
Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14).
Methods
Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study.
Results
Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m2. In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy.
Conclusion
Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.
doi:10.5045/kjh.2012.47.1.53
PMCID: PMC3317471  PMID: 22479278
Bortezomib; CHOP-14; Diffuse large B-cell lymphoma
10.  Frontal Sinus Lymphoma Presenting As Progressive Multiple Cranial Nerve Palsy 
Yonsei Medical Journal  2011;52(6):1044-1047.
Primary frontal sinus lymphoma is a very uncommon disease. In all the previously reported cases, the presenting symptoms have been due to the tumor mass effect. We present an unusual case report of an immunocompetent patient who presented with facial palsy, and then progressively developed other cranial nerve palsies over several months. He was later diagnosed with diffuse large B cell lymphoma originating from the frontal sinus. The patient underwent chemotherapy, but eventually had to receive autologous peripheral blood stem cell transplantation. He is currently disease-free. The clinical course, diagnostic workup, and therapeutic outcome are described.
doi:10.3349/ymj.2011.52.6.1044
PMCID: PMC3220265  PMID: 22028175
Frontal sinus; lymphoma; multiple cranial nerve palsy
11.  Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy 
Background
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes. The aim of this study was to evaluate whether lymphopenia at diagnosis would have an adverse effect on survival in patients with PTCL-NOS treated with anthracycline-containing chemotherapy.
Methods
A total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included.
Results
Thirty-six patients (30.5%) had a low absolute lymphocyte count (ALC, < 1.0 × 109/L) at diagnosis. Patients with lymphopenia had shorter overall survival (OS) and progression-free survival (PFS) rates compared with patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores and lymphopenia were both associated with shorter OS and PFS. Treatment-related mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P = 0.003). In patients considered high-intermediate/high-risk based on IPI scores, lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001, respectively).
Conclusion
This study suggests that lymphopenia could be an independent prognostic marker to predict unfavorable OS and PFS in patients with PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to further stratify high-risk patients using IPI scores.
doi:10.1186/1756-8722-4-34
PMCID: PMC3170642  PMID: 21843362
peripheral T-cell lymphoma; not otherwise specified; lymphopenia; international prognostic index; prognostic factor
12.  Primary CNS lymphoma other than DLBCL: a descriptive analysis of clinical features and treatment outcomes 
Annals of Hematology  2011;90(12):1391-1398.
Diffuse large B-cell lymphoma (DLBCL) constitutes most primary central nervous system (CNS) lymphoma (PCNSL), whereas T-cell, low-grade and Burkitt’s lymphomas (BL) are rarely encountered. Due to the paucity of cases, little is known about the clinical features and treatment outcomes of PCNSL other than DLBCL. The objective of this study was to describe the clinical characteristics and outcomes for patients with PCNSL other than DLBCL. Fifteen patients, newly diagnosed with PCNSLs other than DLBCL between 2000 and 2010, were included. The male to female ratio was 0.67:1 with a median age of diagnosis of 31 years (range 18–59). Pathologic distributions were as follows: peripheral T-cell lymphoma (PTCL; n = 7), marginal zone B-cell lymphoma (MZBCL; n = 1), lymphoplasmacytic lymphoma (LPL; n = 2), Burkitt’s lymphoma (n = 1), other unspecified (T-cell lineage, n = 2; B-cell lineage, n = 2). Thirteen patients (87%) showed Eastern Cooperative Oncology Group performance score (ECOG PS) 1–2. The remaining two were one PTCL patient and one Burkitt’s lymphoma patient. Of the nine patients with T-cell lymphoma, five (56%) had multifocal lesions, and one (20%) with LPL of the five patients with B-cell lymphoma showed a single lesion. Leptomeningeal lymphomatosis was identified in two patients (one with Burkitt’s lymphoma and one with unspecified B-cell lymphoma). Two patients (22%) with T-cell lymphoma died 7.7 and 23.3 months later, respectively, due to disease progression, despite HD-MTX-based therapy. Six patients with T-cell lymphoma (6/9, 66.7%) and four patients with low-grade B-cell lymphoma (4/5, 80%) achieved complete response and have survived without relapse (Table 3). One patient with Burkitt’s lymphoma showed poor clinical features with ECOG PS 3, deep structure, multifocal, and leptomeningeal lymphomatosis, and died 7.6 months after the initiation of treatment. In comparison with previously reported DLBCLs (median OS 6.4 years, 95% CI 3.7–9.1 years), T-cell lymphoma showed equivocal or favorable clinical outcomes and low-grade B-cell lymphomas, such as MZBCL and LPL, had a good prognosis. However, primary CNS Burkitt’s lymphoma presented poor clinical outcomes and showed a comparatively aggressive clinical course. In conclusion, primary CNS lymphoma other than DLBCL occurred more in younger patients and showed a generally good prognosis, except for Burkitt’s lymphoma. Further research on treatment strategies for Burkitt’s lymphoma is needed.
doi:10.1007/s00277-011-1225-0
PMCID: PMC3210363  PMID: 21479535
Primary CNS lymphoma; Diffuse large B-cell lymphoma
13.  Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma 
Neuro-Oncology  2010;12(3):289-296.
The prognosis for patients with recurrent glioblastomas (GBMs) is dismal, with a median survival of 3–6 months. We performed a phase II trial of low-dose continuous (metronomic) treatment using temozolomide (TMZ) for recurrent GBMs. TMZ-refractory patients with GBM who experienced disease recurrence or progression during or after the cyclic treatment schedule of TMZ after surgery and standard radiotherapy were eligible. This phase II trial included 2 cohorts of patients. The initial cohort, comprising 10 patients, received TMZ at 40 mg/m2 everyday. After this regimen seemed safe and effective, the metronomic schedule was changed to 50 mg/m2 everyday. The second cohort, comprising 28 patients, received TMZ at 50 mg/m2 everyday. The 6-month progression-free survival in all 38 patients was 32.5% (95% CI: 29.3%–35.8%) and the 6-month overall survival was 56.0% (95% CI: 36.2%–75.8%). One patient developed a grade III neutropenia, grade II thrombocytopenia in 3 patients, and grade II increase of liver enzyme (GOT/GPT) in 3 patients. Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis. In a response group, quality of life measured with short form-36 was well preserved, when compared with the pretreatment status. Metronomic treatment of TMZ is an effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.
doi:10.1093/neuonc/nop030
PMCID: PMC2940595  PMID: 20167817
glioblastoma; metronomic; recurrent
14.  Schedule-dependent synergistic effect of rituximab on methotrexate chemotherapy against lymphoma of the central nervous system 
We hypothesized that methotrexate (MTX) normalizes the increased permeability of the blood-tumor barrier and thus reduces the accessibility of rituximab (RTX) to central nervous system (CNS) lymphoma. Here, we evaluated the combinational treatment capability of RTX and MTX using an alternative treatment schedule against CNS lymphoma. We developed a CNS lymphoma animal model that closely mimics the morphological and molecular characteristics of human CNS lymphoma by injecting Raji human Burkitt lymphoma cells into the brains of immune-compromised mice and tested a novel combinational treatment schedule by which penetration of RTX was not influenced by MTX administration. RTX was conjugated with Alexa Fluor 680, and its distribution in the brain was analyzed by in vivo imaging. When MTX treatment was followed by a 3-day post RTX administration, RTX was scarcely distributed in the brain, and there were only modest statistically insignificant therapeutic effects compared with the control mice which received sham injections. In contrast, RTX administration followed by a 3-day post MTX treatment showed significantly increased distribution of RTX and significantly reduced tumor volume in the brain. Collectively, our data demonstrate that RTX can be successfully combined with MTX using an alternative treatment schedule that allows increased distribution of RTX in CNS lymphoma.
doi:10.3892/etm.2010.143
PMCID: PMC3445961  PMID: 22993623
central nervous system lymphoma; methotrexate; rituximab; combination therapy; mouse model
15.  Impact of adjuvant chemotherapy for gliomatosis cerebri 
BMC Cancer  2010;10:424.
Background
Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC.
Methods
Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.
Results
Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).
Conclusion
Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.
doi:10.1186/1471-2407-10-424
PMCID: PMC2933624  PMID: 20704759
16.  Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study 
BMC Cancer  2010;10:321.
Background
The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis.
Methods
We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009.
Results
Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 ± 7.6%, and overall survival (OS) was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 ± 5.4% vs. 49.0 ± 15.1%, p = 0.001).
Conclusions
Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.
doi:10.1186/1471-2407-10-321
PMCID: PMC2927999  PMID: 20569446
17.  Systemic EBV+ T-cell lymphoma in elderly patients: comparison with children and young adult patients 
Virchows Archiv  2008;453(2):155-163.
Fulminant Epstein–Barr virus (EBV+) T-cell lymphoma in immunocompetent elderly patients is rare and its character has not been well defined. This study analyzed the clinicopathological features of five elderly patients (group A: 50–84 years) and compared them with those of eight children and young adult patients with systemic T-cell lymphomas (group B: 10–34 years). Group A more commonly presented with generalized lymphadenopathy (n = 3) than did group B (n = 1). Chronic active EBV infection (n = 3) and hydroa vacciniforme-like eruptions (n = 1) were seen in group B, while group A showed no evidence of chronic EBV infection, but did show chronic hepatitis B or C virus infections (n = 3). The histological and immunophenotypical findings were similar. All patients died within 1 to 14 months of diagnosis. These findings suggest that EBV+ T-cell lymphoma in elderly patients is a unique disease with an underlying derangement of T-cell immunity and failure to eradicate infected virus. Additional factors related to senility may play a role in the disruption of homeostasis between the virus and the host’s immune system.
doi:10.1007/s00428-008-0640-7
PMCID: PMC2516298  PMID: 18636273
Epstein–Barr virus; Lymphoma; T-cell
18.  Outcomes of a Modified CALGB 19802 Regimen in Adult Acute Lymphoblastic Leukemia 
Journal of Korean Medical Science  2008;23(2):278-283.
We analyzed the efficacy and toxicity of a modified Cancer and Leukemia Group B (CALGB) 19802 regimen in adult acute lymphoblastic leukemia (ALL). From February 2002 to August 2005, 25 adults with untreated ALL were enrolled in the study. Compared to the original regimen, the modified CALGB 19802 regimen consisted of a 4-drug induction (cyclophosphamide, daunorubicin, vincristine, and prednisone) instead of a 5-drug induction (L-asparaginase was added to the previous regimen). This was followed by high-dose methotrexate (1,000 mg/m2×3 days) and cytarabine (2,000 mg/m2×4 days) for the consolidation cycles. High-dose systemic and intrathecal methotrexate was given for central nervous system prophylaxis. Twenty-three patients (92%) achieved a complete remission (CR), and two patients (8%) had refractory disease. With a median follow-up of 21.5 months, 10 patients (40%) were alive and continued to be in CR. The 3-yr probability of an event-free survival and the overall survival were 39.0% and 47.4%, respectively. Treatment related mortality and major grade 3 to 4 neurotoxicity occurred in 1 patient and 3 patients, respectively. The modified CALGB 19802 regimen demonstrated a high remission rate and a favorable survival rate.
doi:10.3346/jkms.2008.23.2.278
PMCID: PMC2526435  PMID: 18437012
Precursor Cell Lymphoblastic Leukemia-Lymphoma; Drug Therapy
19.  The Spectrum of Epstein-Barr Virus-Associated Lymphoproliferative Disease in Korea: Incidence of Disease Entities by Age Groups 
Journal of Korean Medical Science  2008;23(2):185-192.
This study is to identify the spectrum of Epstein-Barr virus (EBV)-positive lymphoproliferative diseases (LPD) and relationships between these diseases in Korea. The EBV status and clinicopathology of 764 patients, including acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV (CAEBV) infections, B-LPD arising in chronic latent EBV infection, T & natural killer (NK) cell non-Hodgkin's lymphomas (NHL), B-NHLs, and Hodgkin's lymphomas (HD), were analyzed. T or NK cell NHLs were the most common forms of EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell lymphomas were the most common (89/107, 83%). According to the age, Burkitt's lymphoma was the most common in early childhood; in teenagers, chronic (active) EBV infection-associated LPD was the most common type. The incidence of NK/T cell lymphoma began to increase from the twenties and formed the major type of EBV-associated tumor throughout life. Diffuse large B cell lymphoma formed the major type in the sixties and seventies. In conclusion, primary infections in early childhood are complicated by the development of CAEBV infections that are main predisposing factors for EBV-associated T or NK cell malignancies in young adults. In old patients, decreased immunity associated with old age and environmental cofactors may provoke the development of peripheral T cell lymphoma, unspecified, and diffuse large B cell lymphoma.
doi:10.3346/jkms.2008.23.2.185
PMCID: PMC2526432  PMID: 18436998
Lymphoma; Epstein-Barr Virus; Lymphohistiocytosis, Hemophagocytic
20.  A Case of Deep Vein Thrombosis and Pulmonary Thromboembolism after Intravenous Immunoglobulin Therapy 
Journal of Korean Medical Science  2007;22(4):758-761.
Although high-dose intravenous immunoglobulin (IVIG) is generally considered a safe medication for various immune-mediated diseases, thrombotic events have been reported as a complication of the therapy. We report a case who developed thrombotic complications after receiving IVIG. A 56-yr-old woman with idiopathic thrombocytopenic purpura received IVIG at a dose of 400 mg/kg/day for five days. Three days after the administration of IVIG, the patient developed painful edema in the left leg. Lower extremity doppler ultrasound revealed deep vein thrombosis in the left leg. Chest computed tomography (CT) scan demonstrated a filling defect indicating thromboembolism of the right pulmonary artery. After three weeks of enoxaparin therapy, her symptoms and pulmonary embolism on CT improved. This case suggests clinicians should be cautious in the development of thromboembolism by administration of IVIG, especially in patients with thrombophilia.
doi:10.3346/jkms.2007.22.4.758
PMCID: PMC2693835  PMID: 17728525
Intravenous Immunoglobulins; Idiopathic Thrombocytopenic Purpura; Deep Vein Thrombosis; Pulmonary Embolism
21.  Orbital Infiltration as the First Site of Relapse of Primary Testicular T-cell Lymphoma 
A 43-year-old male presented with a painless left testicular mass. The pathologic diagnosis of the radical orchiectomy specimen was peripheral T-cell lymphoma, unspecified (PTCL-u). According to the Ann Arbor staging system, his initial stage was III because of the right nasopharyngeal involvement. After first-line chemotherapy with four courses of the CHOP regimen and this was followed by involved-field radiotherapy, he achieved complete remission. Two months later, disease recurred to the left ciliary body of the left eye without evidence of involvement at other sites. Although the patient received intensive chemotherapy with autologous hematopoietic stem cell transplantation, he ultimately died of leptomeningeal seeding. Because both the central nervous system (CNS) and the orbit are sanctuary sites for chemotherapy, orbital infiltration of lymphoma should prompt physicians to evaluate involvement of the CNS and to consider performing prophylactic intrathecal chemotherapy as a treatment option.
doi:10.4143/crt.2007.39.1.40
PMCID: PMC2739356  PMID: 19746228
Non-Hodgkin's lymphoma; T cell lymphoma; Testes; Eye neoplasm
22.  Paclitaxel with Cisplatin as Salvage Treatment for Patients with Previously Treated Advanced Transitional Cell Carcinoma of the Urothelial Tract 
Neoplasia (New York, N.Y.)  2007;9(1):18-22.
Abstract
BACKGROUND
This study was performed to evaluate the safety and efficacy of paclitaxel with cisplatin as salvage therapy in patients previously treated with gemcitabine and cisplatin (G/C) for advanced transitional cell carcinoma (TCC) of the urothelial tract.
METHODS
Twenty-eight patients with metastatic or locally advanced TCC who had received prior G/C chemotherapy were enrolled. All patients received paclitaxel (175 mg/m2) and cisplatin (60 mg/m2) every 3 weeks for eight cycles or until disease progression.
RESULTS
The median age was 61 years (range, 43–83 years), and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2). The overall response rate was 36% [95% confidence interval (95% CI) = 18–54], with three complete responses and seven partial responses. The median time to progression was 6.2 months (95% CI = 3.9–8.5), and the median overall survival was 10.3 months (95% CI = 6.1–14.1). The most common Grade 3/4 nonhematologic and hematologic toxicities were emesis (10 of 28 patients; 36%) and neutropenia (5 of 110 cycles; 5%).
CONCLUSIONS
Salvage chemotherapy with paclitaxel and cisplatin displayed promising results with tolerable toxicity profiles in patients with metastatic or locally advanced TCC who had been pretreated with G/C.
PMCID: PMC1804323  PMID: 17325740
Paclitaxel; cisplatin; transitional cell carcinoma; salvage therapy; urothelium
23.  Mouse Orthotopic Lung Cancer Model Induced by PC14PE6 
Purpose
This study was undertaken to investigate in detail the xenograft mouse orthotopic lung cancer model induced by PC14PE6 adenocarcinoma cells.
Materials and Methods
Three cell doses (0.5×106; 1×106; 2×106) of PC14PE6 cells were injected into the lungs of male BALB/c nude mice by the intrathoracic injection method. The lung and other organs, including brain, liver, spleen, kidney, muscle, adrenal gland, and lymph node on knee, were removed and stained with H/E to detect the presence of tumor cells.
Results
The reliable tumorigenicity time in the PC14PE6 adenocarcinoma cell-inoculated BALB/c nude mouse was 10 days after intrathoracic injection. The average life span of the three groups after inoculation was 14 days in the 2×106 cells inoculum group; 25 days in the 1×106 cells inoculum group; and 32 days in the 0.5×106 cells inoculum group. The PC14PE6 adenocarcinoma cells induced orthotopic lung cancer limited within the thorax.
Conclusions
This orthotopic lung cancer model is an efficient cancer model with easy inoculation methods, rapid and high tumorigenicity, and simple monitoring methods for metastasis.
doi:10.4143/crt.2006.38.4.234
PMCID: PMC2741646  PMID: 19771249
Orthotopic; PC14PE6; Lung cancer; Animal model
24.  Pulmonary Complications After Hematopoietic Stem Cell Transplantation 
Journal of Korean Medical Science  2006;21(3):406-411.
Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome.
doi:10.3346/jkms.2006.21.3.406
PMCID: PMC2729942  PMID: 16778380
Infection; Hematopoietic Stem Cell Transplantation; Graft vs. Host Disease
25.  Treatment Outcome of Limited Stage Hodgkin's Disease 
Purpose
The 10-year overall survival rate following conventional treatments for patients with limited-stage Hodgkin's disease (HD) exceeds 90%. However, the clinical features and treatment outcome of HD in Korea have not been extensively characterized due to its low incidence. In this study, we attempted to analyze the treatment outcome of different modalities in limited stage HD patients.
Materials and Methods
Twenty one Hodgkin's disease patients, referred to the Samsung Medical Center between January 1997 and December 2003, were enrolled in this study. Limited stage Hodgkin's disease was subdivided into low and high risk groups. All evaluable patients received treatment.
Results
There were 13 and 8 patients in the low and high risk groups, respectively. Eighteen patients (86%) obtained complete response (CR) and 3 patients (14%) achieved an undetermined complete response (CRu). Fourteen (67%), 4 (19%) and 3 (14%) cases received combination chemotherapy, radiotherapy alone and chemotherapy alone, respectively. Four cases relapsed and 2 obtained a second CR. The 5-year overall and disease-free survival rates were 90 and 72%, respectively, for all patients. The median follow-up duration was 31 months. There was no difference in disease free survival (DFS) between the low and high risk groups. Although 12 cases had neutropenia greater than grade III, none experienced neutropenic fever.
Conclusion
The treatment outcome of limited-stage HD was excellent, regardless to the initial treatment modality.
doi:10.4143/crt.2005.37.1.31
PMCID: PMC2785422  PMID: 19956507
Hodgkin's disease; Limited stage

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