A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (> or =500/microL) and platelets (> or =20,000/microL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cytarabine/*therapeutic use/toxicity ; Disease-Free Survival ; Female ; Granulocyte Colony-Stimulating Factor/*therapeutic use/toxicity ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Vidarabine/*analogs & derivatives/therapeutic use/toxicity

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (> or =500/microL) and platelets (> or =20,000/microL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cytarabine/*therapeutic use/toxicity ; Disease-Free Survival ; Female ; Granulocyte Colony-Stimulating Factor/*therapeutic use/toxicity ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Vidarabine/*analogs & derivatives/therapeutic use/toxicity

The objective of the current study was to investigate the treatment outcomes for the use of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy in adult patients with hemophagocytic lymphohistiocytosis (HLH). Seventeen HLH patients older than 18 yr of age were treated with CHOP chemotherapy. A response evaluation was conducted for every two cycles of chemotherapy. With CHOP chemotherapy, complete response was achieved for 7/17 patients (41.2%), a partial response for 3/17 patients (17.6%), and the overall response rate was 58.8%. The median response duration (RD) was not reached and the 2-yr RD rate was 68.6%, with a median follow-up of 100 weeks. Median overall survival (OS) was 18 weeks (95% CI, 6-30 weeks) and the 2-yr OS rate was 43.9%. Reported grade 3 or 4 non-hematological toxicities were increased serum liver enzyme levels and stomatitis. Grade 3 or 4 hematological toxicities were leukopenia (50.8%), anemia (20%), and thrombocytopenia (33.9%). Neutropenic fever was observed in 21.6% of patients (14/65 cycles), and most of the cases were resolved with supportive care including treatment with broad-spectrum antibiotics. CHOP chemotherapy seems to be effective in adult HLH patients and the toxicities are manageable.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse ; Cyclophosphamide/administration & dosage/adverse effects ; Doxorubicin/administration & dosage/adverse effects ; Female ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase/blood ; Lymphohistiocytosis, Hemophagocytic/*drug therapy ; Male ; Middle Aged ; Prednisone/administration & dosage/adverse effects ; Remission Induction ; Survival Rate ; Treatment Outcome ; Vincristine/administration & dosage/adverse effects

PURPOSE: Calcium ionophore (CI) is used to generate dendritic cells (DCs) from progenitor cells, monocytes, or leukemic cells. The aim of this study was to determine the optimal dose of CI and the appropriate length of cell culture required for acute myeloid leukemia (AML) cells and to evaluate the limitations associated with CI. MATERIALS AND METHODS: To generate leukemic DCs, leukemic cells (4 x 10(6) cells) from six AML patients were cultured with various concentrations of CI and/or IL-4 for 1, 2 or 3 days. RESULTS: Potent leukemic DCs were successfully generated from all AML patients, with an average number of 1.2 x 10(6) cells produced in the presence of CI (270 ng/ml) for 2 days. Several surface molecules were clearly upregulated in AML cells supplemented with CI and IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell stimulatory capacity than untreated AML cells, but the addition of IL-4 did not augment the MLR activity of these cells. AML cells cultured with CI in the presence or absence of IL-4 showed increased levels of apoptosis in comparison to primary cultures of AML cells. CONCLUSION: Although CI appears to be advantageous in terms of time and cost effectiveness, the results of the present study suggest that the marked induction of apoptosis by CI limits its application to the generation of DCs from AML cells.
Apoptosis ; Calcium* ; Cell Culture Techniques ; Cost-Benefit Analysis ; Dendritic Cells ; Humans ; Interleukin-4 ; Leukemia, Myeloid, Acute ; Monocytes ; Stem Cells

BACKGROUND: In multiple myeloma (MM), the idiotype (ID) determinant of the paraprotein has been used for immunotherapy using dendritic cells (DCs). However, ID-specific immune responses showed limited clinical responses after the Id vaccination. Therefore, an alternative approach using DCs pulsed with other tumor antigens is required. METHODS: We investigated the possibility of immunotherapy for MM using myeloma cell line-specific cytotoxic T lymphocytes (CTLs), that were stimulated in vitro by monocyte-derived DCs pulsed with the myeloma cell line ysates. CD14+ cells isolated from the peripheral blood of HLA-A0201+ healthy donors were cultured in the presence of GM-CSF and IL-4. On day 6, the immature DCs were pulsed with the myeloma cell line lysates (IM-9: HLA0201+ and ARH-77: HLA0201+), and then maturation of DCs was induced by the addition of TNF- alpha for 2 days. CTL lines were generated by a 2 time stimulation with DCs to the autologous CD3+ T cells. RESULTS: DCs pulsed with myeloma cell lysates showed the production of IL-12p70, but less than that of unpulsed DCs. CTLs lines stimulated with the DCs pulsing, for the myeloma cell line lysates, showed potent cytotoxic activities against autologous target cells, but not against HLA-A2-cell lines (RPMI-8226). Mature DCs pulsed with the myeloma cell line lysates showed a higher stimulatory capacity for autologous CTL when compared with mature non-pulsed DCs. CONCLUSION: These results suggest that DCs pulsed with the myeloma cell line lysates can generate potent myeloma cell line-specific CTLs for the myeloma cell-based immunotherapeutic approach in MM.
Antigens, Neoplasm ; Cell Line* ; Dendritic Cells* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunotherapy ; Interleukin-4 ; Multiple Myeloma ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic* ; Tissue Donors ; Vaccination

Ileovesical fistula is a very rare clinical entity, the most frequent cause of which is Crohn's disease. Furthermore, it is an exceptionally rare complication of malignancies. We experienced one case of ileovesical fistula which had been caused by hepatocellular carcinoma (HCC) arising from the noncirrhotic liver. A 27-year-old man was diagnosed with HCC in a noncirrhotic liver. Despite treatment with transarterial chemoembolization (TACE), the disease status became more aggravated. The patient complained of dysuria, fecaluria, and intermittent lower abdominal pain. Pelvic CT scan showed a soft tissue mass of 6 cm abutting on the distal ileum which was downwardly displaced. Barium study of the small bowel showed a fistula between the small bowel loop and the urinary bladder. Upon operation, adhesion and fistula were found between the ileum and the urinary bladder. The microscopic findings of the surgical specimen were compatible with metastatic HCC. We confirmed that ileovesical fistula had been caused by metastatic HCC.
Adult ; Bladder Fistula/*etiology ; Carcinoma, Hepatocellular/*complications ; Humans ; Ileal Diseases/*etiology ; Intestinal Fistula/*etiology ; Liver Neoplasms/*complications ; Male

Colonic muco-submucosal elongated polyp (CMSEP) is a rare disease which has been firstly reported by Matake. Only 21 cases have been reported since 1994. Although the mechanism of generation of such polyps remains unknown, their elongation may be caused by intestinal motion for a long period. The occurrence sites were distributed throughout the colon, excluding the rectum. CMSEP is coverd with normal mucosa and consisted of edematous, loose, fibrous, connective tissue and dense, fibrous submucosal layer, often dilatation of blood vessels and lymphatics. We present a case of CMSEP diagnosed by a colonoscopic polypectomy.
Blood Vessels ; Colon* ; Colonic Polyps ; Colonoscopy ; Connective Tissue ; Dilatation ; Mucous Membrane ; Polyps* ; Rare Diseases ; Rectum

BACKGROUND: Cardiovascular disease (CVD) after kidney transplantation is a major cause of both graft loss and patient death in kidney transplant recipeints. There are several well known risk factors of CVD, such as hyperlipidemia, hypertension, diabetes melitus, old age and smoking. Non-classic risk factors are acute rejection episode, LVH, C-reactive protein and hyperhomocysteinemia. Homocysteine is an amino acid filtered through the glomerulus and hyperhomocysteinemia is considered as a risk factor of CVD in end-stage renal disease (ESRD) and kidney transplant patients. So homocysteine lowering trials, such as folic acid and vitamine supplement therapy, are being made. We evaluated the prevelance and determinants of hyperhomocysteinemia in kidney transplant recipients. METHODS: We measured serum total homocysteine concentration (tHcy) and its determinants in 21 normal persons, 37 chronic renal failure (CRF) patients with conservative treatment (predialysis) and 48 kidney transplant patients. RESULTS: The prevalence of hyperhomocysteinemia was 4.8%, 83.8% and 45.8% among normal persons, predialysis and kidney tranplant patients, respectively. Among the kidney transplant recipients the prevelence of hyperhomocysteinemia was 18.8% in normal renal function (serum creatitine concentration male: below 1.2 mg/dL, female: below 1.1 mg/dL) group and 59.4% in abnormal renal function group. The tHcy values in kidney transplant patients are significantly lower than those in predialysis patients (16.38+/-6.48 nmol/L vs. 24.68+/-9.01 nmol/L, p < 0.01), but higher than those in normal persons (16.38+/-6.48 nmol/L vs. 8.80+/-2.07 nmol/L, p < 0.01). Among the kidney transplant recipients the tHcy values in normal creatinine group are significantly lower than those in abnormal creatinine group (12.02+/-3.68 nmol/L vs. 18.57+/-6.51 nmol/L, p < 0.01). Using muliple regression analysis, this study showed increased serum creatinine concentration is a major determinant of tHcy concentrations in kidney transplant recipients and hyperhomocysteinemia is not correlated with whole blood trough level of cyclosporin (mean 126.26+/-62.19 ng/mL, range: 26~322 ng/mL) or vitamines supplement therapy. CONCLUSION: In this study the serum homocysteine values in kidney transplant recipients were higher than in normal control group but significantly lower than in CRF patients with conservative treatment. The major determinant for serum homocysteine concentration is a serum creatinine concentration.
C-Reactive Protein ; Cardiovascular Diseases ; Creatinine ; Cyclosporine ; Female ; Folic Acid ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Hyperlipidemias ; Hypertension ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney* ; Male ; Prevalence ; Risk Factors ; Smoke ; Smoking ; Transplantation* ; Transplants ; Vitamins

BACKGROUND: Deregulated bcl-2 appears to prolong cell survival and to cooperative with c-myc in promoting cell proliferation. We investigated whether there is any clinicopathologic correlation between the survival and the frequency of bcl-2/JH rearrangement and bcl-2, c-myc protein expression in non-Hodgkin's lymphoma. METHODS: We conducted a study for bcl-2 mbr/JH rearrangement with polymerase chain reaction and for bcl-2, c-myc expression with immunohistochemical staining in 46 formalin-fixed, paraffin-embedded non-Hodgkin's lymphoma tissues of patients treated with CHOP chemotherapy including 37 specimens of diffuse large cell type. RESULTS: The bcl-2 mbr/JH rearrangement was positive in 13% (6/46) of non-Hodgkin's lymphoma specimens. For bcl-2, strong positive reaction (3+) and 2+ positive reaction were seen in 16 (35%) and 16 cases (35%), respectively; while 3+ and 2+ reactions were found in 20 (44%) and 16 cases (35%), respectively, for c-myc by immunohistochemistry. Eighty one percent of positive cases for bcl-2 were also positive for c-myc simultaneously. The 6 cases with bcl-2 mbr/JH rearrangement were weakly positive at 3 cases and strong positive at 3 cases for bcl-2 by staining. In cases of diffuse large cell lymphoma, high expression (3+) of bcl-2 & c-myc protein tended to have a shorter 2 year survival, though it was statistically not significant. CONCLUSION: High expression of bcl-2 and c-myc protein suggest that bcl-2 cooperate with c-myc in tumorigenesis of aggressive non-Hodgkin's lymphoma. The prognostic implication of bcl-2 and c-myc expression in diffuse large cell lymphoma patients needs to be evaluated in a larger, prospective cohort to draw a definitive conclusion.
Carcinogenesis ; Cell Proliferation ; Cell Survival ; Cohort Studies ; Drug Therapy ; Humans ; Immunohistochemistry ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Non-Hodgkin* ; Polymerase Chain Reaction

To overcome poor graft function after allogeneic bone marrow transplantation (BMT), the use of peripheral blood stem cells (PBSC) instead of bone marrow is gaining more popularity because of its advantages. There may, however, be an increased risk of graft-versus-host-disease (GVHD) because of the large number of lymphocytes present in a leukapheresis product. An 18-year-old man with severe aplastic anemia underwent an allogeneic BMT using his HLA-identical sister. After initial excellent graft take for 8 months, his blood counts gradually decreased to 2.8 x 10(9)/L of white cells and 28 x 10(9)/L of platelets with marrow cellularity of < 10%. After allogeneic granulocyte-colony stimulating factor mobilized PBSC rescue, the patient's blood counts recovered satisfactorily. Around 1 year after the boost, he developed chronic GVHD that responded to prednisolone and cyclosporin A. He is now well on low-dose steroids at day +1055 after PBSC rescue. The present case is the first experience of a long-term follow-up who underwent allogeneic PBSC rescue in Korea.
Adolescence ; Anemia, Aplastic/therapy ; Anemia, Aplastic/blood ; Bone Marrow Transplantation/adverse effects* ; Chronic Disease ; Cyclosporine/therapeutic use ; Female ; Graft vs Host Disease/pathology ; Graft vs Host Disease/etiology* ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Human ; Male ; Prednisolone/therapeutic use