In Vitro Effect of Interleukin-11 (IL-11) on Megakaryopoiesis from Umbilical Cord Blood Cells

BACKGROUND: The megakaryopoiesis and platelet production is regulated by several hematopoietc factors such as thrombopoietin (TPO), interleukin-11 (IL-11) and interleukin-3 (IL-3). IL-11 is a potent stimulator of megakaryopoiesis in vivo, and acts primarily as a megakaryocyte maturation factor in vitro and it can act synergistically with IL-3 and TPO. We performed this study to investigate the effects of recombinant human IL-11 (rhIL-11) with other hematopoietic factors on megakaryocyte colony formation in vitro. METHODS: CD34+ cells were separated from umbilical cord blood and megakaryocyte colonies using MegaCult Assay Kit were cultured with rhIL-11, recombinant human IL-3 (rhIL-3), and recombinant human TPO (rhTPO) for 7 and 14 days. The number and percentage of CD34+ and CD41a+ cells were determined by flowcytometry. RESULTS: The number of CD41a+ cells were 0.54+/-0.05x10(4) (rhIL-11 100 ng/ml), 5.32+.-0.23x10(4) (rhIL-3 100 ng/ml), and 8.76+/-0.15x10(4) (rhTPO 50 ng/ml) of total expanded cells during the culture of the purified CD34+ cells in liquid phase for 7 days. The number of CD41a+ cells were increased to 7.47+/-0.69x10(4) (rhIL-3 rhIL-11), 11.92+/-0.19x10(4) (rhTPO rhIL-11) of total expanded cells, respectively, during the culture of the purified CD34+ cells in liquid phase for 7 days in the presence of rhIL-11 (100 ng/ml). When the purified CD34+ cells were cultured in semisolid media including various concentration of rhIL-11, the megakaryocyte colonies were not formed. When the purified CD34+ cells were cultured with rhIL-11 and rhTPO or with rhIL-11 and rhIL-3, the number of megakaryocyte colonies were increased compared with rhTPO or rhIL-3 alone. CONCLUSION: These results indicate that IL-11 exerts a potent proliferative activity to colony forming unit-megakaryocyte from human umbilical cord blood, and it acts with other hematopoietic factors synergistically

Increased Expression of Fas Antigen and Apoptosis in Aplastic Anemia Bone Marrow Cells

BACKGROUND: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-gamma) and TNF-alpha can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. METHODS: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-gamma, TNF-alpha, or macrophage inflammatory protein 1-alpha (MIP-1alpha). RESULTS: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-gamma, TNF-alpha, or MIP-1alpha increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-gamma, TNF-alpha, or MIP-1alpha mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-gamma enhanced apoptosis most strongly via Fas-caspase-3 pathway. CONCLUSION: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-gamma can induce apoptosis of bone marrow progenitors in part by Fas induction.

Remission Induction by Arsenic Trioxide in Patient with Relapsed Acute Promyelocytic Leukemia after Allogeneic Bone Marrow Transplantation / 대한혈액학회지

All-trans retinoic acid (ATRA) therapy induces complete remission in acute promyelocytic leukemia (APL) via differentiation of the APL cells. Recent clinical trials in China and United states showed that arsenic trioxide (ATO) is an effective and relatively safe drug in the treatment of APL. The patient was 29-year-old woman with APL who had been treated heavily with allogeneic bone marrow transplantation (BMT) in 4 years ago and reinduction chemotherapy plus donor lymphocyte infusion (DLI) after relapse in 2 years ago. After diagnosis for relapse, she had been treated with ATRA, but unfortunately failed. She was treated with ATO at the dose of 10 mg/day intravenously for 6 weeks. Complete remission was achieved at 3 weeks and the cumulative dose of ATO during induction was 420mg. She had complete remission without severe adverse effects except mild impairment of liver function and is following up for 6 months. We report a case of remission induction by ATO in ATRA refractory APL patient who experienced multiple relapse after allogeneic BMT, chemotherapy and DLI.

Atypical Hairy Cell Leukemia / 대한혈액학회지

We experienced a case of atypical hairy cell leukemia in a 42-year-old woman. She showed marked splenomegaly without palpable lymphadenopathy. Complete blood cell count revealed leukocytosis at 44,000/micro L with lymphocytes 74% and peripheral blood smear showed abnormal lymphoid cells with cytoplasmic projections. The bone marrow was easily aspirated and also revealed the abnormal lymphocytes in up to 95%. Tartrate-resistant acid phosphatase reactivity was negative in the hairy cells. Immunophenotyping results of lymphoid cells were CD5(-), CD7(-), CD10(-), CD19(+), and HLA-DR(+). She was treated with an adenosine analogue, fludarabine at a daily dose of 30mg/m2 for 5 consecutive days, every four weeks. Immediately after treatment, the size of the spleen was normalized. Correct diagnosis was difficult due to insufficient laboratory and pathologic data. The differential diagnosis of mature B-cell neoplasms with cytoplasmic projections in patients with splenomegaly includes hairy cell leukemia and splenic lymphoma with villous lymphocytes. We herein described the present case with a brief review of the literature.

High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Persistent/Relapsed Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: High dose chemotherapy (HDC) is increasingly being used for ovarian cancer. Although early studies of autotransplantation for advanced ovarian cancer have been encouraging, most reported series were small, and no randomized trials have been reported. HDC and autologous hematopoietic stem cell transplantation were rarely performed in patients with ovarian cancer in Korea, and no results have been reported with the exception of one case report. MATERIALS AND METHODS: We retrospectively analyzed 10 patients with refractory or relapsed ovarian cancer having received HDC and autologous peripheral blood stem cell transplantation (APBSCT), between January 1996 and September 1998, at the Soon Chun Hyang and Ajou University Hospitals. RESULTS: Ten patients were treated with HDC and APBSCT. Six patients achieved complete response (CR) and 1 a partial response (PR), with a response rate of 70%. Three patients did not respond following mobilization chemotherapy, and failed to respond after HDC. The median duration of progression free survival (PFS) and overall survival (OS) were 6 (4~46) and 13 (3~50+) months, respectively. The median duration of OS of the responders following mobilization chemotherapy was 23 (8~50+) compared with 12 (3~18) months of the non- responders. With regard to the treatment related toxicity, 8 patients had neutropenic fevers, and bacteremia was documented in 4. The non-hematological toxicities were never life threatening, and there were no treatment related deaths. CONCLUSION: HDC, followed by APBSCT, is well-tolerated patients with refractory or relapsed ovarian cancer, and following mobilization chemotherapy the responders survived longer than the non-responders.

Metastasis to the Thigh Skeletal Muscle from an Adenocarcinoma of the Duodenum / Journal of the Korean Cancer Association, 대한암학회지

Skeletal muscle is one of the most unusual metastatic sites for any malignancy. Duodenal cancer is extremely rare, and no cases of skeletal muscle metastasis from duodenal cancer have been reported. We report here in a case of metastasis to the skeletal muscle of the left thigh from duodenal cancer. Our patient was a 47-year-old man, exhibiting a painful mass in the posterior aspect of his left thigh over a 4 month period. An imaging study, and a biopsy, revealed a duodenal adenocarcinoma metastasize to the skeletal muscle. The patient refused chemotherapy and has followed up for 4 months.

Partial Splenic Embolization Therapy of Chronic Idiopathic Thrombocytopenic Purpura / 대한혈액학회지

BACKGROUND: Initial treatment of chronic idiopathic thrombocytopenic purpura (ITP) is generally done with corticosteroid. In case of refractory to corticosteroid or dependency, splenectomy seems to be the most effective and definitive treatment. Partial splenic embolization is an easier procedure with minimal morbidity. We evaluated the efficacy and complications of partial splenic embolization as treatment of chronic ITP refractory to corticosteroid or corticosteroid dependency. METHODS: Eight patients with chronic ITP and two systemic lupus erythematosus (SLE) patients with immunothrombocytopenia underwent partial splenic embolization. Embolization of 70~80% of the splenic volume was performed with endocoils or gelform particles without anesthesia by selective arterial catheterization and followed up for 4~50 months. The therapeutic effect of partial splenic embolzation was defined on the basis of the platelet count at the last follow-up after partial splenic embolzation : complete response, >100,000/nL,partial response, 100,000~50,000/nL and no response, <50,000/nL without medication. RESULTS: Partial splenic embolization brought a complete response in six of ten patients, a partial response in three, and no response in one. With a follow-up of 4~50 months, these responses were maintained in all except three patients. One patient was treated by splenectomy and one by partial splenic embolization again. Tolerance was good in all patients. Abdominal pain and fever was observed in 8 and 4 patients, respectively. One patient had a left pleural effusion with spontaneous resolution. No serious infection occurred. All patients were discharged within 6 days after partial splenic embolization. CONCLUSION: We conclude that partial splenic embolization may be useful and safe procedure and a good alternative to splenectomy in chronic ITP refractory to medical treatment.

Pathophysiologic Study of Aplastic Anemia by Long-term Bone Marrow Cultures / 대한혈액학회지

BACKGROUND: Several mechanisms have been proposed to account for bone marrow failure in aplastic anemia (AA), including deficiency in hematopoietic stem cells, a secondary stem cell defect involving immune regulation and defective marrow stroma, or microenvironment. We investigated the pathophysiology of AA through long-term bone marrow cultures (LTBMCs) using bone marrrow of AA patients before treatment and of patients responded to immunosuppressive therapy with anti-thymocyte globulin (ATG) and/or cyclosporine. METHODS: We investigated the hematopoietic defect in severe aplastic anemia (SAA) patients by using long-term bone marrow cultures (LTBMCs). Twenty patients with SAA have been studied. In these patients, 10 had been treated with ATG plus cyclosporine and the remainders were studied before therapy was begun. Subsequent assays of the production of negative-acting hematopoietic cytokines (TNF-alpha, IFN-gamma, MIP-1alpha and TGF-beta) by AA stroma in LTBMCs were performed. RESULTS: Initial assessment of CD34+ cells, CFU-GM and CFU-MK from LTBMCs in AA demonstrated severely reduced or absent in patients with SAA, even following hematologic recovery with immunosuppressive therapy,when compared with normal controls. Significant difference in concentrations of TNF-alpha, INF-gamma, and MIP-1alpha between the AA and control groups were apparent. Interestingly, the levels of those negative-acting hematopoietic cytokines were decreased in SAA patients receiving immunosuppressive therapy, but not the levels of controls. However, the mean TGF-beta concentrations in the AA patients and normal controls were not significantly different. The percent of CD34+ cells and CFU-MK in bone marrow was lower in SAA patients before immunosuppressive therapy was begun than that in SAA patients receiving immunosuppressive therapy and that in normal controls (mean 0.54+/-0.32% vs 0.96+/-0.32% vs 1.94+/-0.61%). CONCLUSIONS: These results indicate the presence of a in vitro functional deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment, and add to the available evidence for defect of microenvironment with hematopoeitic stem cell in some cases of AA.

A Case of Malignant Proliferating Trichilemmoma of the Scalp with Multiple Metastases

We report a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. The patient demonstrated a round mass in the right occipital area for 12 months and the lesion grew rapidly to assume 8x6.5x4cm in diameter, with areas of superficial erosion and crusting within the recent 3 months. The entire lesion was removed with a wide surgical excision. It recurred on the neck area 4 months after excision and the lesion was removed with surgical resection again. There was evidence of multiple metastases on CNS and mediastinal lymph nodes after 6 months. The patient was treated with cisplatin and etoposide combination chemotherapy and a partial response was achieved.

Clinical significance of kaposi's sarcoma-associated herpesvirus(KSHV) infection in patients of multiple myeloma / 대한내과학회지

BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) been shown to be associated with human diseases including Kaposi's sarcoma, pleural effusion lymphoma, multicentric Castleman's disease. The IL-6 may both stimulate myeloma growth and prevent apoptosis of malignant plasma cells. Interestingly, viral IL-6(vIL-6), homolog to human interleukin-6(IL-6) in KSHV genome retains biologic activity. Thus, oncogenic role of the KSHV has been proposed as a pathogenesis of the multiple myeloma. We used ISH to determine the frequency of patients with multiple myeloma and plasmacytosis associated with KSHV-infected BM cells in fresh core biopsies and to determine the correlation between KSHV infection and clinical characteristics. METHODS: Bone marrow(BM) biopsy samples from 16 cases of multiple myeloma, 2 cases of monoclonal gammopathy of undetermined significance(MGUS) were obtained from the pathology division of Soon Chun Hyang University Hospital, Seoul, Korea. Biopsy sample of Kaposi's sarcoma for positive control and BM biopsy samples of myelodysplastic syndrome(MDS) and malignant lymphoma for negative control were obtained. Bitinylated probe to KSHV were prepared with the following sequences: 5' to 3' TGCAGCAGCTGTTGGTGTACCACATATCT. and in situ hybridization (ISH) was performed. RESULTS: Among the 18 patients. Two patients were MGUS and among 16 patients with multiple myeloma, 1 in stage IB disease, 1 stage IIB disease, 8 stage IIIA disease, 4 stage IIIB diseases and 2 in variant of multiple myeloma, extramedullary plasmacytoma. Strong positive signal was detected in nuclei and cytoplasm of the malignant cells of biopsy sample from 1 cases of Kaposi's sarcoma by ISH(positive control). Signal was not detected in BM biopsy samples of 7 cases from MDS and malignant lymphoma(negative control). Among 16 patients with multiple myeloma, 15 demonstrated viral positive cells and 2 cases with MGUS also showed viral positive cells by ISH. Signal was detected in nuclei and cytoplasm of stromal cells. Signal was strongly detected in MGUS than multiple myeloma. Positivity of the KSHV was not related with stage of the patients with multiple myeloma. One patients with multiple myeloma was studied at diagnosis and after chemotherapy. After chemotherapy KSHV was not detected. CONCLUSION: In MGUS and multiple myeloma, KSHV infects the stromal cells of BM rather than malignant plasma cells. On the basis of these data, we have supposed KSHV to play a role in transformation from MGUS to multiple myeloma. Particularly, due to the fact that signal of ISH was strongly detected in MGUS and was not detected in one case with multiple myeloma, it was presumed that KSHV was not major role in already advanced multiple myeloma but statistic significance was not demonstrated because of small numbers of cases. Further studies to reveal the correlation of KSHV and pathogenesis of multiple myeloma are needed.

Clinical Significance of bcl-2 and p53 protein Expression in Patients with Malignant Lymphoma / 대한혈액학회지

BACKGROUND: Overexpression of bcl-2 protein is observed both in follicular lymphoma, in which bcl-2 has usually undergone a translocation t (14;18). The experimental findings that transfection of bcl-2 in to murine lymphoid cells confers resistance to nitrogen mustard and camptothecin by inhibiting apoptosis suggests that bcl-2 overexpression may confer clinical drug resistance in lymphomas. In contrast to bcl-2, p53 arrests cells exposed to DNA-damaging agents in G1 to allow DNA repair or if essential repairs are not possible, promotes apoptosis. Experimentally, loss of p53 function produces cellular resistance to alkylating and topoisomerase-II drug classes, suggesting that loss of p53 function in lymphomas may cause drug resistance. These observations led to the hypothesis that bcl-2 and p53 play a role in the development of drug resistance in lymphoma. Although several studies assessed the association between bcl-2 expression and disease-free survival, they reached conflicting conclusions. METHODS: We analyzed tumor tissue from 42 patients with advanced NHL for p53 and bcl-2 expression and correlation with multiple clinical characteristics, response to therapy and overall survival. Among 42 tumors, 8 (19.0%) tumors had bcl-2 expression and 19 (45.2%) had a p53 overexpression. RESULTS: A significant correlation was found between bcl-2 expression and poor performance, advanced stage (stage III and IV) at diagnosis, and bone marrow involvement in a univariate analysis (P50%) were more likely to be poor prognosis than tumors with negative or week expression (<50%) and to have a shorter long-term survival (28.6% vs 75.5%; P<0.05). However, the expression of p53 did not correlate with any clinical characteristics and overall survival was not influenced by p53 protein expression. CONCLUSION: These results suggest that bcl-2 protein expression in patients with malignant lymphoma appears to be predictive of shorter long-term survival and it might be considered as a strong independent prognostic factor.

Telomerase Activity in HL-60 Cells After Treatment with Differentiating Agents / 대한혈액학회지

BACKGROUND: Telomeres are repetitive DNA fragments at the termini of chromosomes functioning as stabilizing elements of the DNA. A ribonucleoprotein polymerase, called telomerase, is responsible for the synthesis of such telomeric repeats in embryo and germ cells. During ontogenesis of most normal human somatic cells, there exists a physiological telomerase repressing mechanism. In contrast, malignant cells are characterized by an unlimited progressive potential. Certain physiological agents, such as all-trans retinoic acid (ATRA), 13-cis retinoic acid (13-cisRA), 1alpha-25 dihydroxy vitamin D3 (VD3) and cytosine arabinoside (Ara-C), promote further differentiation of leukemic cells into mature granulocytes and monocytes and subsequently undergo apoptosis. METHODS: To determine if a potential linkage is present between telomerase regulation and the differentiation of malignant hematopoietic cells, the changes in telomerase activity during the maturation of HL-60 cells induced by ATRA, 13-cisRA, VD3 and Ara-C were investigated. RESULTS: Differentiating agents induce HL-60 cells to differentiate into CD11b+ granulocytes and monocyte/macrophages, respectively. Approximately 98% of HL-60 cells acquired the expression of CD11b+ antigen after ATRA, 13-cisRA or Ara-C treatment for 5 days. After 1 day treatment with differentiating agents, no significant difference in telomerase activity was shown between untreated and treated HL-60 cells. A dramatic inhibition of telomerase activity occurred at 3 days treatment of ATRA compared to untreated HL-60 cells. Longer treatment for 5 days with differentiating agents resulted in further decrease of telomerase activity. However, telomerase activity in HL-60 cells was decreased slightly by the VD3 or Ara-C treatment, even though for 5 days. No evidence of differentiation and slight decrease of telomerase activity were observed in ATRA-treated K-562 cells for 5 days. These decrease of telomerase activity were dependent on the incubation time and dose. CONCLUSION: These data clearly show the role of telomerase activity during the differentiation of HL-60 cells. This in vitro model can be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.

Clinical Value of Plasma Vascular Endothelial Growth Factor in Patients with Stomach Cancer / 대한내과학회지

OBJECTIVE: Angiogenesis is an essential step in growth and metastasis of solid tumors. Vascular endothelial growth factor(VEGF) is one of the most important mediators of angiogenesis. VEGF selectively stimulates endothelial cell proliferation and induces angiogenesis. Also VEGF was expressed by several human solid tumors and serum VEGF levels have previously been shown to be raised in patients with breast cancer, gastrointestinal cancer, renal cancer and melanoma. To evaluate the clinical value of plasma VEGF of patients with stomach cancer we studied correlations between plasma VEGF, tumor stage, tumor resection and microvessel invasion by tumor. METHODS: VEGF level was measured by ELISA methods in plasmas from 88 patients and after surgical tumor resection from 48 patients with gastric carcinoma. Microvessel staining was done by immunohistochemical staining using anti-CD34 monoclonal antibody on paraffin embedded tissues. RESULTS: The plasma VEGF levels were significantly higher in the stomach cancer patients than in normal controls(p<0.0001). In stomach cancer patients, plasma VEGF level was significantly increased according to stage progression(p<0.05). Moreover early cancer, T1, showed a significantly elevation of plasma VEGF level than that of controls. The level of plasma VEGF fell after surgical resection(n=48) of stomach cancer(p<0.05). Also the plasma VEGF levels were significantly higher in microvessel invasion by tumor(n=25) than in those without invasion(n=19)(p<0.05). CONCLUSION: In conclusion, plasma VEGF may be useful for predicting disease status and prognosis of patients with stomach cancer.

A case of CMV disease of the jejunum in a patient with non-Hodgkin's lymphoma

CMV infection may occur anywhere in the gastrointestinal tract. Among the small intestine, ileum is the most common site of CMV disease and infection of jejunum is a rare one in patients with CMV gastroenteritis. Although rare, the reason why the recognition of this diagnosis is important is that it cause the lethal hemorrhage and perforation of gastrointestinal tract when its diagnosis and treatment was delayed. Rapid diagnosis are able to using the immunohistochemical stain in shell vial culture of infected specimen or peripheral neutrophils preparation in viremic patients within 8 to 36 hours. The treatment of choice is antiviral agent or surgical resection. We experienced a case of CMV disease of jejunum in patient with non-Hodgkin's lymphoma who showed severe ulceration in jejunum and massive intestinal hemorrhage, and he survived after successful treatment with segmental resection of jejunum and intravenous ganciclovir.

A Comparison of the Acute Antiemetic Effect of Tropisetron with Ondansetron in Patients Receiving Cisplatin / 대한암학회지

PURPOSE: Tropisetron, a new specific 5-hydroxytryptamine3 (5-HT3) receptor antagonist, is an effective antiemetic agent in the control of chemotherapy induced emesis with a long half life and bioavailablity. We compared the efficacy and safefy of Tropisetron and ondansetron to control emesis induced by highly emetogenic chemotherapeutics (cisplatin > or = 50 mg/m(2)). MATERIALS AND METHODS: Twenty-one patients were administered in a randomized, open, crossover study and received either tropisetron plus dexamethasone or ondansetron plus dexamethasone during two successive cycles of chemotherapy. RESULTS: Control of acute emesis with either tropisetron or ondansetron was 100% vs 95.2%, and 80.9% vs 76.2% in control of delayed emesis. Both severity and duration of nausea showed no statistically significant difference between tropisetron and ondansetron. Poor appetite and headache were most common side effects in both groups. CONCLUSION: There was no significant difference in efficacy for control of emesis and nausea between tropisetron and ondansetron in cisplatin-based chemotherapy.

A Case of Primary Splenic Angiosarcoma Associated with Kasabach-Merritt Syndrome / 대한암학회지

PURPOSE: Primary malignant vascular neoplasms of the spleen are rare. It has been known that the prognosis was very poor and the splenectomy before rupture could increase survival. No effective chemotherapeutic protocol for angiosarcomas has yet to be established but patients with or without metastatic disease may be treated by chemotherapy. MATERIAL AND METHODS: We experienced a case of primary splenic angiosarcoma in a 42-year-old woman with multiple purpuric skin rashes associated with consumptive coagulopathy:the Kasabach-Merritt syndrome. The CT showed spleen is diffusely enlarged and inhomogenously enhanced with multiple metastasis in the liver. The splenectomy was done and angiosarcoma was diagnosed. We treated her with conventional combination chemotherapy and obtained partial response. For additional response, high-dose chemotherapy and stem cell rescue with autologous peripheral blood stem cell transplantation was done. RESULT: Afer splenectomy, platelet count return to normal. The follow up abdominal CT scan after treatment showed complete disappeared multiple metastatic lesions in the both lobe of liver and the patient has continued to do well four months following discharge. CONCLUSION: We herein report our experience of a splenic angiosarcoma whose multiple hepatic metastases responded well to the high-dose chemotherapy.

The Expression of Fas Antigen and Apoptosis in Patients with Myelodysplastic Syndromes and Its Clinical Relevance / 대한혈액학회지

BACKGROUND: The myelodysplastic syndromes (MDS) are a group of acquired clonal hematopoietic disorders characterized by the peripheral cytopenias and hypercellular or normocellular dysplastic bone marrow. The event responsible for the development of MDS is generally not known. Several recent reports have described an increased frequency of apoptosis in bone marrow cells from patients with aplastic anemia or MDS. Gersuk et al observed that Fas ligand expression was significantly increased on bone marrow cells from MDS patients as compared to normal individuals. METHODS: We examined apoptosis and Fas antigen expression using ISNEL method and immunohistochemistry on marrow cells from 36 patients with MDS. RESULTS: Among the 36 patients, 15 patients (42%) demonstrated apoptosis positive cells (>15%) and 9 patients (25%) demonstrated positive Fas antigen expression (>20%). The presence of apoptosis significantly correlated with hemoglobin level at diagnosis (P<0.05) and the expression of Fas antigen significantly correlated with bone marrow cellularity and CD34 positive cell aggregate group at diagnosis (P<0.05). There was no statistically significant relationship between apoptosis and Fas antigen expression. The median survival of all patients with MDS was 44 months (2-117+). Multivariate analysis showed that FAB classification and hemoglobin level at diagnosis were significant prognostic factor but presence of apoptosis and expression of Fas antigen had no significance. CONCLUSION: The data indicate that the apoptosis and expression of Fas antigen are present in patients with MDS and correlate with some clinical parameters but not significantly associated with survival period of the patients with MDS.

A Case of Recurrent Subacute Necrotizing Lymphadenitis with Pancytopenia / 대한혈액학회지

We report a case of recurrent subacute necrotizing lymphadenitis with pancytopenia in 21-years-old-woman. She was admitted to our hospital 4-years interval with fever and abdominal pain. Laboratory findings of the last admission showed pancytopenia, such as WBC 700/microliter, hemoglobin 6.0mmol/L (9.7g/dL), hematocrit 28.8%, and platelet 54,000/microliter. Abdominal CT showed hepatosplenomegaly, enlarged conglomerated lymph nodes in splenic hilum, lesser sac, celiac root, and paraaortic areas. Bone marrow biopsy showed hypocellular marrow (20%) with increased number of megakaryocyte, myeloid hyperplasia, and hemophagocytic histiocytes suggesting infectious process. We performed exploratory laparotomy, and pathologic finding revealed subacute necrotizing lymphadenitis-Kikuchi disease-. She was recovered on 26th hospital day with conservative treatment.

Comparison of Radiation Therapy and Combined Chemotherapy and Radiation Therapy for Locally Advanced Head and Neck Cancer / 대한암학회지

PURPOSE: In locally advanced head and neck cancer, radiation therapy is currently unsatisfactory because the end result is often limited regional disease control and survival. A clinical study was carried out to compare the effectiveness between the radiation therapy and the combined chemotherapy and radiation therapy. MATERIALS AND METHOD: Thirty-six patients with previously untreated, locally advanced squamous cell carcinoma of the head and neck were treated with radiotherapy alone and combined chemo-radiotherapy. Induction chemotherapy was administered 2~3 cycles, consisting of intravenous cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2/day for 5 days as a continuous infusion) every 4 weeks followed by 7~8 weeks of radiation therapy for a total dose of 60~75 Gy. RESULTS: 1) Among 36 locally advanced head and neck cancer, 17 patients received radiation therapy alone and 19 patients received combined chemo-radiotherapy, respectively. 2) Response rate was 47% (complete response 29%, and partial response 18%) in radiation therapy group and 79% (complete response 37%, and partial response 42%) in combined chemo-radiotherapy group (p0.05). 4) Treatment related mortality was not noted, but the toxic effects were seen on the half cases of the both groups. Grade II toxicities were similar between the two arms. CONCLUSION: Combined chemotherapy and radiation therapy was more effective in local control but not superior in survival than radiation therapy alone. Continuous evaluation and identification of proper sequence for the therapeutic modality is supposed to prolong the survival of patients.

Two Cases of Transient Aplastic Crisis Associated with Human Parvovirus Bl9 Infection in Hereditary Spherocytosis and Hereditary Elliptocytosis / 대한임상병리학회지

Among the causes of pure red cell aplasia, human parvovirus B19 has been shown to be cytotoxic to erythroid progenitor cells in the bone marrow associated with chronic hemolytic anemia with rapidly dividing erythroids and persistently to be suppression of erythropoiesis in immunocompromised individuals related with failure to produce neutralizing antibody to the virus. In a patient with hereditary spherocytosis presenting acute onset of reticulocytopenia during hospitalization, who had shown severe anemia and prodromal symptoms including fever, fatigue and dizziness, infection of parvovirus Bl9 was proven by the presence of IgM and IgG antibodies to parvovirus Bl9, the detection of viral DNA using PCR technique in her serum and the decreased erythroid cells, especially late normoblasts in bone marrow, Also in the other who was diagnosed as hereditary elliptocytosis and complained of fever, headache, abdominal pain and diarrhea, an episode of reticulocytopenia and the nearly absence of late normoblasts in the bone marrow were observed. IgM antibodies to parvovirus Bl9 and the viral DNA were detected in her serum, too.