Chul Won Choi

Image-Guided Stereotactic Body Radiation Therapy in Patients With Isolated Para-Aortic Lymph Node Metastases From Uterine Cervical and Corpus Cancer

PURPOSEnThe aims of this study were to evaluate the role of stereotactic body radiation therapy (SBRT) as a local treatment for isolated para-aortic lymph node (PALN) metastases originating from uterine cervical and corpus cancer.nnnMETHODS AND MATERIALSnWe retrospectively enrolled 30 patients with isolated PALN metastases originating from uterine cervical and corpus cancer who had received SBRT using the CyberKnife (CK). All patients were shown to have isolated PALN metastases by computed tomography (CT) and/or positron emission tomography (PET)-CT. The overall survival (OS), local control (LC) rate, and disease progression-free survival (DPFS) rate were calculated according to the Kaplan-Meier method. Comparison between prognosis groups was performed using log-rank analysis. Toxicities were also evaluated.nnnRESULTSnThe 4-year OS rate was 50.1%, and the median survival time was not reached. The OS rate among symptomatic patients was significantly lower than that among asymptomatic patients (p = 0.002). The 4-year actuarial LC rate was 67.4%. Patients with a planning target volume of </=17 ml had significantly higher LC rates (p = 0.009). The 4-year DPFS rate was 45.0%, and the median time to disease progression was 32 months. Small planning target volume was a favorable prognostic factor (p = 0.043). Grade 3 or 4 complications requiring hospitalization were reported in 1 patient at 20 months after SBRT.nnnCONCLUSIONnThe OS and LS rates were promising, and the incidence of toxicities was low. Use of SBRT with the CyberKnife is an effective modality for treating isolated PALN metastases in patients with uterine cervical and corpus cancer.

Response to high-dose intravenous immune globulin as a valuable factor predicting the effect of splenectomy in chronic idiopathic thrombocytopenic purpura patients

This study was conducted to verify whether the response to high‐dose intravenous immune globulin (IVIG) was related to the effect of splenectomy in chronic idiopathic thrombocytopenic purpura (ITP) patients. A total of 79 patients over 16 years of age were enrolled in this study. The response to the treatment was classified on the basis of the platelet count as no response (NR, <50 × 109/l), incomplete response (IR, (50–150) × 109/l), and complete response (CR, >150 × 109/l). The response was evaluated after the infusion of high‐dose IVIG, within 2 weeks after splenectomy (immediate response), and during a follow‐up period of more than 6 months after splenectomy (sustained response), respectively. 58 patients (73.4%) showed responses (CR or IR) to high‐dose IVIG. After splenectomy, immediate responses were observed in 73 patients (92%). The response to high‐dose IVIG had no relationship with the immediate response to splenectomy (P = 0.333). A follow‐up evaluation was possible with 58 patients; 6 patients with NR in immediate responses did not show any response during the follow‐up period, and 17 patients relapsed within 6 months after immediate responses, so 35 patients (60.3%) had sustained responses. Responders to IVIG had significantly higher sustained response rates to splenectomy than non‐responders (62% vs. 38%, P = 0.001). These results indicate that the response to high‐dose IVIG could be a valuable factor predicting the sustained response to splenectomy in chronic ITP patients. Am. J. Hematol. 66:197–202, 2001.

Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study

BackgroundThe 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.MethodsWe retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009.ResultsMedian 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).ConclusionsOur 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.

Serum BAFF predicts prognosis better than APRIL in diffuse large B-cell lymphoma patients treated with rituximab plus CHOP chemotherapy

Objectives:u2002 B‐cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation‐inducing ligand (APRIL) regulate survival and proliferation of B cells. Thus the association of elevated serum levels of BAFF and APRIL with worse prognosis has been suggested in B‐cell lymphoid malignancies. However, the prognostic relevance of BAFF and APRIL is unknown in patients treated with rituximab, a monoclonal antibody targeting B‐cell depletion.

Long-Term Engraftment Stability of Peripheral Blood Stem Cells Cryopreserved Using the Dump-Freezing Method in a −80°C Mechanical Freezer with 10% Dimethyl Sulfoxide

In this study, we summarize our long-term follow-up data of 24 patients who underwent autologous peripheral blood stem cell transplantation (PBSCT) using the dump-freezing method in a −80°C freezer. Collected peripheral blood mononuclear cells were mixed with a cryoprotectant solution consisting of autologous plasma and 20% dimethyl sulfoxide, then placed in a −80°C freezer. The recovery rate of mononuclear cells (MNCs), colony-forming unit—granulocyte/macrophage (CFU-GM) colonies, and CD34+ cells were calculated. Engraftment time (with neutrophil count > 0.5 × 109/L, platelet count > 50 ×109/L) and normal hemopoiesis (neutrophil count > 2 ×109/L, platelet count > 100 ×109/L) were evaluated. Median duration of cryopreservation was 76 days. The mean recovery rates of MNCs, CFU-GM colonies, and CD34+ cells were 93.4%, 78.4%, and 95.3%, respectively. The median engraftment times of neutrophils and platelets were 8 and 27 days, respectively. The median normal hemopoiesis times of neutrophil and platelet were 31 and 45 days, respectively. Nine patients are alive and in complete remission (CR). Seven patients in first CR sustained normal hemopoiesis with a median duration of 35 months. Two patients, who achieved second CR after salvage chemotherapy due to a leukemia relapse after PBSCT, maintained engraftment status for 24 and 28 months, and 1 reached normal hemopoiesis. These results demonstrate that PBSCT using the dump-freezing method in a −80°C freezer leads to acceptable long-term engraftment stability.

The cutoff value of serum ferritin for the diagnosis of iron deficiency in community-residing older persons

The serum ferritin assay is the best single blood test for the diagnosis of iron deficiency. Previous studies with elderly anemic patients have suggested that ferritin level less than 45xa0μg/L is indicative of iron deficiency. The subjects of these studies were hospitalized patients with anemia, however. We thus conducted a prospective study to determine the normal minimum level of serum ferritin of community-dwelling older adults by assessing the ratio of serum transferrin receptor to the log ferritin level (sTfR-F index). We conducted the anemia survey between October and November 2002. A total of 1,254 apparently healthy older adults, aged between 60 and 95 years, from three urban community dwellings participated in the survey. Among these individuals, 156 subjects who were anemic or whose serum ferritin level was less than 100xa0μg/L were selected. The soluble transferrin receptor assay was performed and the sTfR-F index was calculated. The receiver operating characteristic curve analysis was performed. Based on the data, serum ferritin level of 22xa0μg/L was selected as the cutoff value for the diagnosis of iron deficiency in community-dwelling older adults. Applying the serum ferritin cutoff of 22xa0μg/L and the sTfR-F index cutoff of 1.5, the sensitivity of the assay was 89.5% (34 of 38) and the specificity was 89.0% (105 of 118). In conclusion, for the diagnosis of iron deficiency of community-residing older adults, we suggest the serum ferritin cutoff value of 22xa0μg/L obtained by use of the sTfR-F index. The value is lower than the previous value established for hospitalized and anemic older adults.

Secondary central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma: a therapeutic dilemma

Secondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes an isolated CNS relapse or CNS involvement with systemic disease progression. This rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. However, there are limited data about its treatment outcome. In this study, we gathered 73 cases with secondary CNS involvement of DLBCL from 11 hospitals in Korea. The data were retrospectively compared according to the status of systemic disease (isolated vs. combined CNS involvement) and the use of high-dose methotrexate treatment (HD MTX). Twenty-nine patients showed isolated CNS involvement while 44 had combined CNS involvement with systemic relapse or progression. Thirty-three cases (45.2%) occurred within 6xa0months from the initial diagnosis, and the majority of these were associated with systemic disease relapse or progression (nu2009=u200927). In isolated CNS involvement, HD MTX resulted in fewer treatment failures (3/11) than the other treatments such as other salvage chemotherapy and/or radiotherapy/intraventricular chemotherapy (14/15). However, neither HD MTX nor other treatments were effective at reducing the treatment failure rate in combined CNS involvement (8/10 and 23/30, respectively). Thus, isolated CNS involvement had a better survival than combined involvement (Pu2009=u20090.008), but systemic disease progression was the main cause of death in combined as well as isolated CNS involvement. In conclusion, the prognosis of secondary CNS involvement was dismal even after intensive chemotherapy using HD MTX. Further research focusing on the development of an optimal treatment strategy is warranted.

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. Patients and methods: All 53 patients received epirubicin (50xa0mg/m2 i.v.) on day 1 and cisplatin (60xa0mg/m2 i.v.) after epirubicin administration. Oral UFT 400–600xa0mg/day, determined by body surface area, and leucovorin 75xa0mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Results: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0–26.8%) with median response duration of 17.1xa0weeks (95% CI; 5.0–29.3xa0weeks, range; 7.1–51.7xa0weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6xa0weeks (95% CI; 17.3–31.9xa0weeks, range; 3.0–131.3xa0weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). Conclusion: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.

Hematopoietic Differentiation of Embryoid Bodies Derived from the Human Embryonic Stem Cell Line SNUhES3 in Co-culture with Human Bone Marrow Stromal Cells

Human embryonic stem (ES) cells can be induced to differentiate into hematopoietic precursor cells via two methods: the formation of embryoid bodies (EBs) and co-culture with mouse bone marrow (BM) stromal cells. In this study, the above two methods have been combined by co-culture of human ES-cell-derived EBs with human BM stromal cells. The efficacy of this method was compared with that using EB formation alone. The undifferentiated human ES cell line SNUhES3 was allowed to form EBs for two days, then EBs were induced to differentiate in the presence of a different serum concentration (EB and EB/high FBS group), or co-cultured with human BM stromal cells (EB/BM co-culture group). Flow cytometry and hematopoietic colony-forming assays were used to assess hematopoietic differentiation in the three groups. While no significant increase of CD34+/CD45- or CD34+/CD38- cells was noted in the three groups on days 3 and 5, the percentage of CD34+/CD45- cells and CD34+/CD38- cells was significantly higher in the EB/BM co-culture group than in the EB and EB/high FBS groups on day 10. The number of colony-forming cells (CFCs) was increased in the EB/BM co-culture group on days 7 and 10, implying a possible role for human BM stromal cells in supporting hematopoietic differentiation from human ES cell-derived EBs. These results demonstrate that co-culture of human ES-cell-derived EBs with human BM stromal cells might lead to more efficient hematopoietic differentiation from human ES cells cultured alone. Further study is warranted to evaluate the underlying mechanism.

Clinical features and treatment outcomes of adult B- and T-lymphoblastic lymphoma: results of multicentre analysis in Korea

We performed a retrospective multicentre analysis to study the clinical features and treatment outcomes of B-lymphoblastic lymphoma (B-LBL) and T-lymphoblastic lymphoma (T-LBL) in Asian adult patients, and identify risk factors that predict relapse and poor prognosis. Fifty-five newly diagnosed patients (45 T-LBL and 10 B-LBL) were analysed. All patients were treated with intensive chemotherapy regimens including VPDL (vincristine, prednisolone, daunorubicin, L-asparaginase), CALGB (Cancer and leukemia group B), and Stanford/Northern California Oncology Group (NCOG). There was no difference of clinical features between B- and T-LBL except the frequent site of involvement. The overall response rate including complete response (28/55, 50.9%) and partial response (18/55, 32.7%) was 83.6%. Among 46 responders, 22 patients relapsed leading to 20 deaths. Partial responders showed more frequent relapse (10/18, 55.6%) than complete responders (11/28, 39.2%). The median progression-free survival (PFS) was 17 months (95% confidence interval, 11.5–22.5), and the 2-year overall survival was 52 ± 7% with a median follow-up of 50 months (range 8–152). Treatment outcome of T-LBL and B-LBL was not significantly different in terms of response and survival. The presence of pleural effusion was significantly prognostic for overall and PFS (p < 0.05). In conclusion, clinical features and treatment outcome of Asian adult LBL were comparable to previous results, and the prognosis is still poor despite intensive chemotherapy.