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1.  Simplified flow cytometric immunophenotyping panel for multiple myeloma, CD56/CD19/CD138(CD38)/CD45, to differentiate neoplastic myeloma cells from reactive plasma cells 
The Korean Journal of Hematology  2012;47(4):260-266.
Background
Flow cytometric immunophenotyping has been used to identify neoplastic plasma cell populations in patients with multiple myeloma (MM). Previous reports have described the use of several antigens, including CD38, CD138, CD56, CD117, CD52, CD19 and CD45, to distinguish distinct populations of plasma cells. The aim of this study was to evaluate a simplified immunophenotyping panel for MM analysis.
Methods
A total of 70 patients were enrolled in the study, 62 of which were newly diagnosed with MM (untreated), whereas the remaining 8 were undergoing bone marrow assessment as part of follow-up after treatment (treated). Treated cases included 3 patients with relapse and 5 patients with persistence of MM. Multiparametric flow cytometric immunophenotyping was performed using monoclonal antibodies against CD56, CD19, CD138 (CD38), and CD45.
Results
In differential counts, plasma cells in bone marrow (BM) accounted for 3.6-93.2% of the total nucleated cell count. The positive expression rates of CD56, CD19, CD138, and CD45 in neoplastic myeloma cells were 83.9%, 0%, 98.4%, and 37.1%, respectively, among the 62 untreated cases, and 75.0%, 0%, 87.5%, and 37.5%, respectively, among the 8 treated cases. CD19 expression of neoplastic plasma cells was negative in both untreated and treated cases.
Conclusion
The simplified immunophenotyping panel, CD56/CD19/CD138(CD38)/CD45, is useful for distinguishing neoplastic myeloma cells from reactive plasma cells in clinical practice. In addition, CD19 represents the most valuable antigen for identifying neoplastic myeloma cells in patients with MM.
doi:10.5045/kjh.2012.47.4.260
PMCID: PMC3538797  PMID: 23320004
Multiple myeloma; Flow cytometry; Immunophenotyping; Neoplastic plasma cells; CD19 negativity
2.  Clinical characteristics and outcomes of primary bone lymphoma in Korea 
The Korean Journal of Hematology  2012;47(3):213-218.
Background
This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL).
Methods
We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed.
Results
The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions.
Conclusion
Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.
doi:10.5045/kjh.2012.47.3.213
PMCID: PMC3464339  PMID: 23071477
Bone lymphoma; Radiotherapy; Rituximab
3.  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
5.  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
6.  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
7.  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

Results 1-7 (7)