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2.  Yttrium-90 ibritumomab tiuxetan plus busulfan, cyclophosphamide, and etoposide (BuCyE) versus BuCyE alone as a conditioning regimen for non-Hodgkin lymphoma 
The Korean Journal of Hematology  2012;47(2):119-125.
Background
Radioimmunotherapy agents have a highly significant role in autologous stem cell transplantation as they improve tolerability and increase the efficacy of the conditioning regimen.
Methods
We retrospectively analyzed the efficacy and toxicity of yttrium-90 ibritumomab tiuxetan (Zevalin) combined with intravenous busulfan, cyclophosphamide, and etoposide (Z-BuCyE) compared with those of BuCyE alone followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The efficacy, toxicity, and engraftment characteristics were compared between 19 patients who received Z-BuCyE and 19 historical controls who received BuCyE.
Results
The 2 treatment groups shared similar baseline characteristics. The median time to platelet engraftment (>20×109/L) and neutrophil engraftment (>0.5×109/L) did not significantly differ between the Z-BuCyE group (12 days and 10 days, respectively) and the BuCyE group (12 days and 10 days, respectively). No significant differences were observed between the groups with respect to toxicities and treatment-related mortality. The median follow-up period was 30.4 months, and median event-free survival was generally better in the Z-BuCyE group (12.5 months) vs. the BuCyE group (6.2 months, P=0.236). No significant difference in overall survival between the groups was noted.
Conclusion
Adding ibritumomab tiuxetan to BuCyE high-dose chemotherapy may benefit patients with relapsed or refractory B-cell NHL with no risk of additional toxicity.
doi:10.5045/kjh.2012.47.2.119
PMCID: PMC3389060  PMID: 22783358
Yttrium-90 ibritumomab tiuxetan; BuCyE; Autologous stem cell transplantation; Non-Hodgkin lymphoma
3.  Epidemiologic overview of malignant lymphoma 
The Korean Journal of Hematology  2012;47(2):92-104.
Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend.
doi:10.5045/kjh.2012.47.2.92
PMCID: PMC3389073  PMID: 22783355
Malignant lymphoma; Epidemiology; Asia
4.  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
5.  Relapse pattern and prognostic factors for patients with primary central nervous system lymphoma 
Background
Primary central nervous system lymphoma (PCNSL) rarely relapses in extracranial sites, and no specialized guidelines for follow-up evaluation have been proposed.
Methods
We analyzed 65 patients with newly diagnosed PNCSL to evaluate the pattern of relapse and prognostic factors.
Results
Of the 65 patients analyzed, 55 had only parenchymal brain disease, and 10 had both intracranial and extracranial lesions. As a first-line treatment, 29 patients received chemotherapy only (CTx), 13 received chemotherapy followed by whole brain radiotherapy (CTx-WBRT), 18 received chemotherapy followed by autologous stem cell transplantation (CTx-ASCT), 2 received palliative WBRT, and 3 received best supportive care. The overall response rate to the initial treatment was 75.8%, with specific response rates of 62.1% to CTx, 84.6% to CTx-WBRT, and 100% to CTx-ASCT. The complete response (CR) rate was higher with CTx-ASCT than in the absence of ASCT (77.8% vs. 43.2%; P=0.025). After a median follow-up of 18.8 months, the median failure-free survival (FFS) and overall survival (OS) were 13.0 and 36.1 months, respectively. No systemic relapse without a CNS lesion was noted. Multivariate analysis showed that ASCT was predictive of better FFS but not of OS. Age and the Memorial-Sloan Kettering Cancer Center prognostic score were predictive of survival.
Conclusion
We observed no systemic relapse without a CNS lesion, suggesting that regular systematic evaluation of extracranial sites may not always be necessary. Age was prognostic of survival irrespective of treatment scheme. ASCT may improve CR rate and FFS.
doi:10.5045/kjh.2012.47.1.60
PMCID: PMC3317473  PMID: 22479279
Primary CNS lymphoma; Relapse; Prognostic factor
6.  Addition of rituximab to the CHOP regimen has no benefit in patients with primary extranodal diffuse large B-cell lymphoma 
The Korean Journal of Hematology  2011;46(2):103-110.
Background
The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP) has significantly improved clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL). However, new predictors of patient response to R-CHOP have not been established. We aimed to evaluate the impact of R-CHOP compared with CHOP in patients with DLBCL and to establish clinical predictors of better outcomes in these patients.
Methods
We retrospectively identified 177 patients diagnosed with CD20-positive DLBCL and treated with CHOP (N=82) or R-CHOP (N=95). The response rate, event-free survival (EFS), and overall survival (OS) rates were compared between the 2 treatment groups. All patients were classified into primary extranodal lymphoma (PENL) or nodal lymphoma (NL) subgroups, and the clinical parameters of each subgroup were analyzed.
Results
The overall response rate was higher in R-CHOP group (95% vs. 84%, P=0.07). The 3-year EFS rate was significantly higher in R-CHOP group (71% vs. 52%, P=0.013), but the OS rate was comparable between the 2 groups (79% vs. 69%, P=0.23). A significant survival benefit was seen with R-CHOP compared to CHOP therapy in NL patients (P=0.002 for EFS and 0.04 for OS). Multivariate analyses confirmed that R-CHOP therapy is an independent prognostic factor for EFS (hazard ratio of 0.32 [0.17-0.62], P=0.001) and OS (hazard ratio of 0.4 [0.18-0.87], P=0.02) in NL patients.
Conclusion
Patients in the PENL group did not benefit from R-CHOP chemotherapy.
doi:10.5045/kjh.2011.46.2.103
PMCID: PMC3128890  PMID: 21747882
CHOP; Diffuse large B-cell lymphoma; Rituximab; Primary extranodal lymphoma
7.  Image analytic study of nuclear area in mantle cell lymphoma 
The Korean Journal of Hematology  2010;45(3):193-196.
Background
Malignant lymphomas are classified on the basis of morphology, immunohistochemistry, and genetic and molecular biological features. Morphology is considered the most important and basic feature. Lymphomas can be classified as small, medium, or large depending on the cell size, but this criterion tends to be rather subjective. The aim of this study was to investigate the usefulness of an objective approach based on quantitative measurements.
Methods
Twenty specimens of mantle cell lymphoma and 2 specimens of the tonsil were examined. The nuclear area of 6,401 tumor cells of mantle cell lymphoma and 743 normal mantle cells of reactive tonsils were measured by 3 authors by using a user-controlled image-analyzer. The images of the nuclei were outlined using the spline method and the i-solution software, and the data were assessed using ANOVA and Student's t-test.
Results
The mean nuclear areas of mantle cell lymphoma cells measured by the 3 authors were 37.9 [7.9] µm2, 37.9 [7.2] µm2, and 38.2 [7.7] µm2 and those of normal mantle cells in reactive tonsil were 28.6 [2.3] µm2, 28.8 [2.0] µm2, and 27.0 [3.0] µm2. There was no statistical difference between the 3 observations of mantle cell lymphoma (P=0.580) and normal tonsils.
Conclusion
For morphology, nuclear area is considered an important feature in the classification schemes of lymphoma. We showed that nuclear area measurement by using image analyzer can be used as an objective quantitative method. We think that nuclear morphometry may play a significant role in the diagnosis of lymphoma.
doi:10.5045/kjh.2010.45.3.193
PMCID: PMC2983036  PMID: 21120209
Image analysis; Morphometry; Nuclear area; Mantle cell lymphoma

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