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1.  Cellular immunotherapy using dendritic cells against multiple myeloma 
Cellular therapy with dendritic cells (DCs) is emerging as a useful immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype vaccination was recently suggested to induce idiotype-specific immune responses in MM patients. However, the clinical results so far have been largely disappointing, and the clinical effectiveness of such vaccinations in MM still needs to be demonstrated. DC-based therapies against MM may need to be boosted with other sources of tumor-associated antigens, and potent DCs should be recruited to increase the effectiveness of treatment. DCs with both high migratory capacity and high cytokine production are very important for effective DC-based cancer vaccination in order to induce high numbers of Th1-type CD4+ T cells and CD8+ cytotoxic T lymphocytes. The tumor microenvironment is also important in the regulation of tumor cell growth, proliferation, and the development of therapeutic resistance after treatment. In this review, we discuss how the efficacy of DC vaccination in MM can be improved. In addition, novel treatment strategies that target not only myeloma cells but also the tumor microenvironment are urgently needed to improve treatment outcomes.
doi:10.5045/kjh.2012.47.1.17
PMCID: PMC3317466  PMID: 22479274
Cellular immunotherapy; Dendritic cell; Multiple myeloma; Cytotoxic T lymphocyte; Immune response
2.  Fludarabine-containing chemotherapy for patients with previously untreated low-grade non-Hodgkin's lymphoma 
The Korean Journal of Hematology  2011;46(3):180-185.
Background
The clinical efficacy and safety of fludarabine combination chemotherapy was investigated for the treatment of previously untreated patients with low-grade (NHL).
Methods
Twenty-five patients who were newly diagnosed as low-grade NHL were treated with fludarabine combination chemotherapy. Fludarabine combination regimens consisted of fludarabine, mitoxantrone and dexamethasone or fludarabine, cyclophosphamide and mitoxantrone with or without rituximab and repeated every 4 weeks.
Results
The median age was 60 years (range, 35-77 years), with 13 of 25 patients (52%) ≥60 years of age. Seven of 25 patients (28%) with an intermediate risk follicular lymphoma international prognostic index (FLIPI) and 9 of 25 patients (36%) with a high risk FLIPI were enrolled in this study. The delivered median number of chemotherapy was six (range, 2-9 cycles). The overall response rate with fludarabine-based treatment was 88%, including 52% complete remission and 36% partial remission. During the median follow-up of 19 months, the estimated 2-year event-free survival was 63±10% (95% CI, 43-83) and the 2-year overall survival was 78±9% (95% CI, 60-96). Fludarabine combination chemotherapy was frequently associated with grade 3 or 4 neutropenia in 84% patients. However, neutropenic infection was observed in only one (4%) patient. Four patients (16%) showed grade 3 or more non-hematologic toxicities, such as acute coronary syndrome, intracranial hemorrhage, anaphylaxis and gastric cancer.
Conclusion
Fludarabine-combination treatment was a highly active regimen with well toleration in untreated low-grade NHL.
doi:10.5045/kjh.2011.46.3.180
PMCID: PMC3208201  PMID: 22065973
Fludarabine; Primary; Lymphoma
3.  Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients 
Background
All-trans retinoic acid (ATRA)/anthracycline chemotherapy is beneficial in newly diagnosed acute promyelocytic leukemia (APL); however, it is important to identify patients with high-risk disease to increase the cure rate. We investigated the outcome of ATRA/anthracycline chemotherapy and clinicobiological correlations of FLT3/ITD and NPM1 mutations in APL patients.
Methods
Induction therapy included oral ATRA (45 mg/m2/day) and idarubicin (12 mg/m2/day, intravenous, on days 2, 4, and 6). Patients achieving complete remission (CR) received 3 courses of ATRA combined with reinforced consolidation therapy. Mutations were analyzed using GeneScan and polymerasae chain reaction assays of bone marrow samples obtained from patients at diagnosis.
Results
Forty-five (84.9%) of 53 eligible patients achieved CR. The overall relapse rate was 8.9%, and the 3-year overall survival (OS) and leukemia-free survival (LFS) were 84.9±4.9% and 77.5±6.0%, respectively. The NPM1 mutation was not found in any patient, while the FLT3/ITD mutation was found in 10 (20.0%) patients. Of the FLT3/ITD+ patients, 80% belonged to the high-risk group, defined according to the presenting WBC and platelet counts. Among the patients who achieved CR, those who were FLT3/ITD+ had a higher relapse rate than those FLT3/ITD-. FLT3/ITD+ patients also had a significantly lower 3-year LFS than FLT3/ITD- patients. Multivariate analysis of the LFS showed that the FLT3/ITD mutation was independently associated with a shorter overall LFS, after adjusting for pretreatment risk stratification.
Conclusion
This study investigated the clinical outcome of newly diagnosed APL patients treated with ATRA/anthracycline chemotherapy. Patients carrying the FLT3/ITD mutation had more aggressive clinical features and a poorer clinical outcome.
doi:10.5045/kjh.2011.46.1.24
PMCID: PMC3065622  PMID: 21461300
Acute promyelocytic leukemia; FLT3; Prognosis
4.  Prognostic significance of nucleophosmin mutations and FLT3 internal tandem duplication in adult patients with cytogenetically normal acute myeloid leukemia 
Background
Nucleophosmin (NPM1) gene and fms-like tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) mutations are the most frequent mutations in patients with cytogenetically normal (CN)-AML. We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML.
Methods
NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by GeneScan and PCR assays of bone marrow samples obtained from 121 adult patients with CN-AML (age≤60 years at diagnosis).
Results
The incidence of FLT3-ITD+ was higher in the NPM1mut group than in the wild-type NPM1 gene (NPM1wt) group. The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups. The isolated NPM1mut group showed significantly better clinical outcomes in terms of relapse rate, 5-year relapse-free survival (RFS), and overall survival (OS) than the other groups. In contrast, the isolated FLT3-ITD+ group had a higher relapse rate and shorter RFS and OS than the other groups. The 5-year RFS rate was much higher among the patients who underwent allogeneic stem cell transplantation (alloSCT) than among those treated with high-dose cytarabine chemotherapy (HDAC) only as consolidation therapy in the isolated NPM1mut group and the NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD- group.
Conclusion
Adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.
doi:10.5045/kjh.2010.45.1.36
PMCID: PMC2983002  PMID: 21120161
NPM1; FLT3-ITD; Acute myeloid leukemia; Normal karyotype

Results 1-4 (4)