Typhlitis is a life threatening necrotizing enterocolitis of the cecum, ascending colon and terminal ileum seen in severely neutropenic patients, however its pathogenesis is not identified up to this time.The incidence of typhlitis in leukemic patient is 10~12%, estimated by postmortem examination, and 46% in induction chemotherapy of leukemia. Recently, entity incidence is more high due to increasing challenges to high dose chemotherapy in solid tumors.We experienced four cases of typhlitis, one was developed in the circumstance of neutropenia induced by induction chemotherapy for acute myelocytic leukemia and others in neutropnia due to primary diseases without chemotherapy, ig, chronic myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome.All cases were treated with high dose broad spectrum antibiotics in early phase of disease and its outcome was good, so that, early diagnosis of typhlitis is essential, then prompt treatment with high dose antibiotics and intravenous fluid before onset of transmural necrosis is associated with lower morbidity and mortality than surgical resection.
Anti-Bacterial Agents ; Autopsy ; Cecum ; Colon, Ascending ; Drug Therapy ; Early Diagnosis ; Enterocolitis, Necrotizing ; Humans ; Ileum ; Incidence ; Induction Chemotherapy ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Mortality ; Necrosis ; Neutropenia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Typhlitis*

PURPOSE: Tuberculosis may cause a serious complication in children with cancer who are receiving the chemotherapy. But its diagnosis is not easy if we do not suspect the disease in patients with uncontrolled persistent fever. We studied retrospectively the importances of prevention and early diagnosis of tuberculosis in cancer patients. METHPDS: Twelve patients were diagnosed as having tuberculosis during cancer chemotherapy in Kyungpook National University Hospital from May, 1981 to May, 1998. We reviewed their clinical features, diagnostic methods, treatment and prevention. RESULTS: The median age of the patients was 14 (2~18) years. The underlying diseases were seven acute lymphoblastic leukemia (ALL), two acute undifferentiated leukemia (AUL), one acute nonlymphoblastic leukemia (ANLL), one mixed-lineage leukemia, and one Burkitt's lymphoma. The disease categories of tuberculosis were seven pulmonary tuberculosis, two tuberculous pleurisy, one miliary tuberculosis, one bone and endotracheal tuberculosis and one tuberculous meningitis. The family history of tuberculosis is positive in one case. The clues of the suspicion of tuberculosis infections were 9 cases of persistent fever despite broad spectrum of antibiotics and/or antifungal agent therapy, 2 chronic cough and 1 chest pain. We could diagnose four by AFB culture, three cases by AFB smear, two by polymerase chain reaction (PCR), one by pleural biopsy, one by transbronchial lung biopsy and one by chest X-ray and CSF study. We treated pulmonary tuberculosis and tuberculous pleurisy by triple therapy (isoniazid, rifampin, pyrazinamide) and miliary, bone, endotracheal tuberculosis and tuberculous meningitis by quadriple therapy (isoniazid, rifampin, pyrazinamide, streptomycin or kanamycin). The mean duration of defervescence after treatment was 15.4 days. One died of fulminant hepatitis probably by hepatitis B after completion of cancer chemotherapy, one died of adult respiratory distress syndrome, two died of DIC, three died of relapse of underlying disease, but no one died of tuberculosis infection itself. CONCLUSION: The early diagnosis of tuberculosis is an important factor for decreasing the mortality rates of cancer patients, so we should have a suspicion of this disease in patients with persistent fever in spite of appropriate antibiotic and antifungal agents. Isoniazid prophylaxis may be needed in childhood cancer patients with chemotherapy in Korea.
Anti-Bacterial Agents ; Antifungal Agents ; Biopsy ; Burkitt Lymphoma ; Chest Pain ; Child ; Cough ; Dacarbazine ; Diagnosis ; Drug Therapy* ; Early Diagnosis ; Fever ; Gyeongsangbuk-do ; Hepatitis ; Hepatitis B ; Humans ; Isoniazid ; Korea ; Leukemia ; Leukemia, Myeloid, Acute ; Lung ; Mortality ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Pyrazinamide ; Recurrence ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Rifampin ; Streptomycin ; Thorax ; Tuberculosis* ; Tuberculosis, Meningeal ; Tuberculosis, Miliary ; Tuberculosis, Pleural ; Tuberculosis, Pulmonary

BACKGROUND: It has been demonstrated that flow cytometric detection of minimal residual disease (MRD) has a prognostic significance in the treatment of patients with acute leukemia. We investigated the significance of flow cytometric MRD detection for the first time in Korea. METHODS: We analyzed the results of MRD detection in morphologically complete remission bone marrow aspirates from 89 patients with newly-diagnosed or relapsed acute leukemia, in which leukemic cells had cross-lineage antigen expression. Patients were grouped based on MRD frequencies: > or =1.0%, high MRD; <1.0%, low MRD. RESULTS: Forty-seven ALL patients consisted of 10 with high and 37 with low MRD levels. Patients with high MRD levels showed a tendency of more frequent relapse than those with low MRD levels (40.0% and 13.5%, respectively) (P=0.08). High MRD group showed a tendency of short relapse-free survival (RFS) and overall survival (OS), although the differences were not statistically significant. Forty-two AML patients consisted of 16 with high and 26 with low MRD levels. There were no correlations between the MRD levels and relapse rate, RFS or OS. AML patients with high MRD levels showed significantly higher rate of unfavorable cytogenetic risk categories and lower rate of favorable risk categories (P=0.03). CONCLUSIONS: MRD detection by flow cytometric assay of cross-lineage antigen expression would be useful in predicting treatment outcome in patients with ALL rather than AML. We expect that the establishment of the standardization of methods, time to test or antibody combination would be achieved through further trials in this country.
Acute Disease ; Adolescent ; Adult ; Aged ; Antigens/*metabolism ; Antigens, CD/metabolism ; Bone Marrow/metabolism ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; *Flow Cytometry ; Humans ; Infant ; Leukemia, Myeloid, Acute/*diagnosis/mortality/therapy ; Male ; Middle Aged ; Neoplasm, Residual/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/mortality/therapy ; Recurrence ; Survival Rate

PURPOSE: High survival rate can be obtained in B-cell lymphoma (Burkitt's lymphoma, diffuse large B-cell lymphoma) and L3 acute lymphoblastic leukemia (ALL) with multiagent chemotherapy. Objectives of this study were to evaluate the treatment outcomes of B-cell lymphoma and L3 ALL diagnosed at the Department of Pediatrics, Asan Medical Center. METHODS: The medical records of 32 children who were diagnosed with Burkitt's lymphoma, diffuse large B-cell lymphoma and L3 ALL from March 1992 to July 2004 at Asan Medical Center were reviewed retrospectively. The 5 year event free survival (EFS) according to the diagnosis, age, risk group and lactic dehydrogenase (LDH) level were analyzed. RESULTS: There were 23 boys and 9 girls. Age ranged from 9 months to 14.4 years old with a median of 7.1 years. Fourteen patients had L3 ALL, 11 had Burkitt's lymphoma and 7 had diffuse large B-cell lymphoma. Five patients (15.6%) had CNS involvement and 5 with B-cell lymphoma (27.8%, 5/18) had BM involvement. All patients who received appropriate chemotherapy achieved a complete remission (CR), but 18.8% (6/32) relapsed. Among 6 relapsed patients, 5 achieved CR after reinduction chemotherapy. One who had no response to secondary chemotherapy and 2 with isolated CNS relapse died due to disease progression. The most common treatment-related toxicity was myelosuppression (87.5%) followed by neutropenic fever (81.3%). Median follow up is 25 months (3 months to 74 months). Four patients who achieved CR after proper induction therapy (4/32, 12.5%) died, 3 due to relapse and 1 due to toxicity-related complication (neutropenia and sepsis). The 5 year EFS for all patients was 77.5+/-7.5% and the 5 year overall survival was 84.6+/-7.3%. The 5 year EFS of B-cell lymphoma compared with that of L3, ALL was 94.4+/-5.4% versus 55.1+/-13.9% (P=0.012) and 5 year overall survival of relapsed patients was 50.0+/-13.9%. CNS disease at diagnosis, age, LDH had no significant influence on EFS. CONCLUSION: High survival rate of childhood B-cell lymphomas and L3 ALL was obtained with recent intensive multiagent chemotherapy and about 50% of relapsed patients were salvaged with reinduction. High incidence of the treatment-related toxicity such as myelosuppression, neutropenic fever and TLS was observed, but the treatment-related mortality was very low with recent supportive therapies. Survival rate was improved with prompt and appropriate management for the treatment-related toxicity of the intensive chemotherapy.
B-Lymphocytes* ; Burkitt Lymphoma ; Central Nervous System Diseases ; Child ; Chungcheongnam-do ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Female ; Fever ; Follow-Up Studies ; Humans ; Incidence ; Lymphoma, B-Cell* ; Lymphoma, Non-Hodgkin ; Medical Records ; Mortality ; Oxidoreductases ; Pediatrics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome*

Although Aspergillus endocarditis has rarely been reported, it can cause fatal complications in hematologic malignancy patients and allogeneic stem cell transplant recipients. We experienced two cases of aspergillus endocarditis developed in acute lymphoblastic leukemia patients. Case; A 19-year-old patient developed Aspergillus endocarditis after allogenic hemopoietic stem cell transplantation. He was treated with surgical intervention and liposomal amphotericin B. He died of recurred Aspergillus endocarditis and cerebral hemorrhage probably related with aspergillosis of central nervous system. Case 2; A 23-year-old patient developed invasive Aspergillus endocarditis after induction chemotherapy. Aspergillus endocarditis was successfully treated by surgical intervention and amphotericin B. He died of refractory neutropenic fever and sepsis after the third relapse of leukemia and repetitive chemotherapy. He probably had invasive pulmonary aspergillosis without evidence of endocarditis recurrence. Because the mortality of Aspergillus endocarditis is very high, early diagnosis and surgical intervention are very important for better outcome.
Amphotericin B ; Aspergillosis ; Aspergillus* ; Central Nervous System ; Cerebral Hemorrhage ; Drug Therapy ; Early Diagnosis ; Endocarditis* ; Fever ; Hematologic Neoplasms ; Humans ; Induction Chemotherapy ; Invasive Pulmonary Aspergillosis ; Leukemia ; Mortality ; Osteomyelitis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Recurrence ; Sepsis ; Stem Cell Transplantation ; Stem Cells ; Transplantation ; Young Adult

Although Aspergillus endocarditis has rarely been reported, it can cause fatal complications in hematologic malignancy patients and allogeneic stem cell transplant recipients. We experienced two cases of aspergillus endocarditis developed in acute lymphoblastic leukemia patients. Case; A 19-year-old patient developed Aspergillus endocarditis after allogenic hemopoietic stem cell transplantation. He was treated with surgical intervention and liposomal amphotericin B. He died of recurred Aspergillus endocarditis and cerebral hemorrhage probably related with aspergillosis of central nervous system. Case 2; A 23-year-old patient developed invasive Aspergillus endocarditis after induction chemotherapy. Aspergillus endocarditis was successfully treated by surgical intervention and amphotericin B. He died of refractory neutropenic fever and sepsis after the third relapse of leukemia and repetitive chemotherapy. He probably had invasive pulmonary aspergillosis without evidence of endocarditis recurrence. Because the mortality of Aspergillus endocarditis is very high, early diagnosis and surgical intervention are very important for better outcome.
Amphotericin B ; Aspergillosis ; Aspergillus* ; Central Nervous System ; Cerebral Hemorrhage ; Drug Therapy ; Early Diagnosis ; Endocarditis* ; Fever ; Hematologic Neoplasms ; Humans ; Induction Chemotherapy ; Invasive Pulmonary Aspergillosis ; Leukemia ; Mortality ; Osteomyelitis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Recurrence ; Sepsis ; Stem Cell Transplantation ; Stem Cells ; Transplantation ; Young Adult

BACKGROUND: Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukemia in children. However, quality of life and even survival may be threatened by infection. Immunosuppression is experted due to disease itself or therapy, and sometimes, immunosuppression itself may lead to reactivation of latent viral infections in these patients. Often the viruses involved in the most severe infections suggest that patients suffer from defect in the cellular immunity. The principal defects that predispose leukemia patients to infection are defects of T cell, B cell, stem cell, complement, and macrophage. These contributing factors interact in a complex manner resulting in spectrum of problems. But these may result from a T cell defect and, in this study, 7 cell responsiveness of patients at diagnosis, remission induction, maintenance chemotherapy and after chemotherapy for leukemia has been investigated. Studies of the immune competence of patients undergoing chemotherapy for leukemia is in progress, but results are different from each other. METHOD: Between July 1994 and May 1996, seventy patients with childhood ALL were enrolled in this study. In order to expect frequency and depth of infection and prognosis, we investigated concentrations of immunoglobulins G, A, M, peripheral total lymphocyte count, 7 cell subsets, phytohemmaglutinin responsiveness, interleukln-2(IL-2), gamma-interferon(gamma-INF), and natural killer cell activity. RESULTS: 1) IgA concentrations were often markedly raised at diagnosis, and IgG, IgM concentrations both were within normal limits. During and after chemotherapy, IgA had fallen significantly but IgG, IgM are within normal limits. 2) Total lymphocyte count had fallen during chemotherapy, and returned to normal levels after chemotherapy. CD4+ T cell were markedly decresed at diagnosis, during chemotherapy and returned to normal levels after chemotherapy. 3) In vitro proliferative response of peripheral blood lymphocytes to the T cell mitogen phytohenagglutinin were impaired at diagnosis, during chemotherapy but did not returned to normal levels. 4) Interlekin-2, gamma interferon were normal levels at diagnosis, and had fallen in the induction of remission and quickly returned to normal levels with the swish to maintenance chemotherapy. But Interleukin-2 had fallen during and after chemotherapy. Natural killer cell activity had fallen at diagnosis, during chemotherapy and returned to normal levels after chemotherapy. CONCLUSION: It is assumed that evidence of impaired T cell responses is somewhat definite. These observations suggest that proliferative responses to phytohemagglutinin, CD4+ T cell, natural killer cell activity defects are due to leukemia itself but others more likely are generalizable defects caused by chemotherapy. Further investigations, however, have suggested a persisting defect in IgA, proliferative reponses to phytohemagglutinin, and interleukln-2. Our observations also show that despite normal immunoglobulin levels, most of these children have nonprotective levels for common childhood bacterial or viral disease. These results support to the praxis to withdraw prophylactic antibiotics after discontinuation of intensive chemotherapy and to start the immunization. It is expect to try to use cytokine on treatment and to improve mortality and morbidity for children of acute leukemia also.
Anti-Bacterial Agents ; Child* ; Complement System Proteins ; Diagnosis ; Drug Therapy* ; Humans ; Immunity, Cellular ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Immunosuppression ; Interferons ; Interleukin-2 ; Killer Cells, Natural ; Leukemia ; Lymphocyte Count ; Lymphocytes ; Macrophages ; Maintenance Chemotherapy ; Mental Competency ; Mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Prognosis ; Quality of Life ; Remission Induction ; Stem Cells ; Virus Diseases

OBJECTIVEAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, while glucocorticoid (GC) is a critical component in multi-agent chemotherapy protocols currently used for the treatment of ALL. The purpose of this study was to investigate the relationship between the glucocorticoid induction test and the clinical features and the prognosis of Chinese childhood ALL.

METHODThe study recruited 309 hospitalized patients (187 male and 122 female) with childhood ALL, the sex, age, initial WBC count, immunophenotype, chromosome and gene expression were recorded. After diagnosis, all patients received GC induction test for 7 days. Then they were divided into prednisone good response (PGR) group and prednisone poor response (PPR) group according to the peripheral lymphoblast count on D8. Early responses to chemotherapy and treatment outcomes of the patients in the two groups were also analyzed.

RESULTOf the 309 patients, 263 belonged to PGR group and 46 belonged to PPR group. Initial WBC count was higher in PPR group than in PGR group (86.30×10(9)/L vs. 30.97×10(9)/L, P < 0.01) . B lineage ALL showed more sensitive to GC than T-ALL (86.6% vs. 60%, P < 0.05). Different initial-risk-group's sensitivity to GC differed from one another (high-risk:51.4%, medium-risk: 82.7%, standard risk: 93.7%, P < 0.0125). There was no significant difference between two groups in chromosomal karyotypes (P > 0.05). BCR-ABL positive ALL showed lower sensitivity to GC (P < 0.05) , while MLL, TEL-AML1, E2A-PBX1 positive rates in two groups were of no statistical significance (P > 0.05). Bone marrow was reviewed on D15 and D33, and the CR rates in PGR group were significantly higher than that in PPR group (D15: 60.5% vs. 32.6%, D33: 94.6% vs. 73.3%, P < 0.01) ; Minimal residual disease (MRD) levels were examined on D33, W12, and both were much lower in PGR group (D33: P < 0.01, W12: P < 0.05). Of the PGR group 215 patients (81.7%) remained continuously in complete remission (CCR) while only 28 cases (60.9%) in PPR group did so. The CCR rate was much higher in PGR group than that in PPR group (P < 0.01).

CONCLUSIONClosely related to clinical features and the outcomes of treatment, GC induction test is also an important prognostic factor in Chinese childhood ALL.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; Child ; Child, Preschool ; Female ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Leukocyte Count ; Male ; Neoplasm, Residual ; drug therapy ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; genetics ; mortality ; Predictive Value of Tests ; Prognosis ; Remission Induction ; Survival Rate

BACKGROUND/AIMS: We investigated the clinical characteristics and prognosis of elderly patients with acute lymphoblastic leukemia (ALL). METHODS: We reviewed the clinical data, laboratory findings, bone marrow findings, and cytogenetic analysis of elderly patients (> or = 60 years) with ALL, and data of an additional 101 younger adult patients (< 60 years) with ALL were reviewed for comparison. RESULTS: Twenty-six elderly patients (> or = 60 years) and 101 younger adult patients (< 60 years) with ALL were retrospectively enrolled. The median follow-up duration was 6.0 months (range, 0.4 to 113.2) in the elderly patients and 21.7 months (range, 1.0 to 122.7) in the adult patients. In total, 34.6% (9 patients) of the elderly patients and 24.8% (25 patients) of the adult patients had Philadelphia chromosome positive ALL. The overall complete remission (CR) rate was much higher in the younger than in the elderly patients (94.1% vs. 57.7%, p < 0.001). The median overall survival (OS) of the younger patients (< 60 years) was 26.3 months, whereas that of the elderly patients (> or = 60 years) was 10.3 months (p = 0.003). In the elderly patients with ALL, T cell lineage and the presence of lymphadenopathy were significant prognostic factors for OS in a univariate analysis (p = 0.033 and 0.041, respectively). CONCLUSIONS: The outcomes of Korean elderly patients with ALL were poor, and the shorter OS was mainly due to the low CR rate. T-cell lineage and the presence of lymphadenopathy were significant prognostic factors in Korean elderly patients with ALL.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Marrow Examination ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Philadelphia Chromosome ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/drug therapy/genetics/immunology/mortality ; Proportional Hazards Models ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Rate ; Time Factors ; Treatment Outcome ; Young Adult

BACKGROUND: Because of the relative paucity of data regarding the clinical outcome in adult patients with acute lymphocytic leukemia (ALL) in Korea, we analyzed clinical courses in adult ALL patients treated with VPD (L) regimen (vincristine, prednisolone, daunorubicin, L-asparaginase) at the Seoul National University Hospital, and evaluated prognostic factors influencing the outcome. METHODS: Patients with ALL newly diagnosed between October 1994 and June 2000 at our hospital were analyzed retrospectively. Fifty-three patients were evaluable. Induction chemotherapy consisted of VPD with (46 cases) or without L-asparaginase (7 cases). After complete remission (CR), consolidation therapy, CNS prophylaxis and maintenance chemotherapy were administered. RESULTS: Ages ranged from 16 to 67 (median 30). CR rate was 86.8% (46/53) and no significant prognostic factor was found for the CR rate. With a median follow-up time of 27.2 months (range 12.9~83.0 months) in living patients, the median overall survival (OS) for all cases was 16.7 months (13.4~20.1 months, 95% C.I.) and the estimated 4-year OS rate was 25.4%+/-8.9%. The median relapse-free survival (RFS) was 12.2 months (8.4~16.0 months, 95% C.I.), and 3-year RFS rate was 29.9%+/-10.2%. Poor prognostic factors for OS were Ph chromosome (p=0.005) and T-cell immunophenotype (p=0.03). For RFS they were Ph chromosome (p=0.01) and the presence of a mediastinal mass (p=0.03). CONCLUSION: Despite an initial excellent response to the VPD (L) regimen, newer therapeutic strategies, including more intensive postremission therapies, are urgently needed because of the high relapse rate. Future therapeutic approaches need to be stratified according to several prognostic factors.
Administration, Oral ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects ; Asparaginase/*administration & dosage/adverse effects ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Doxorubicin/*administration & dosage/adverse effects ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Male ; Maximum Tolerated Dose ; Middle Aged ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*drug therapy/*mortality ; Prednisone/*administration & dosage/adverse effects ; Probability ; Remission Induction ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; Vincristine/*administration & dosage/adverse effects