Acute myeloid leukemia (AML) is a rare type of childhood acute leukemia, which has a worse prognosis than childhood acute lymphoblastic leukemia. Over the past decade, significant progress has been made in the treatment of childhood AML and the 5-year event-free survival rate may be as high as 70% in developed countries. This survival improvement is largely attributable to risk-stratified treatments, therapies tailored to individual patients based on the biological characteristics of the disease, and continuously improving supportive care. An accurate diagnosis is the prerequisite for risk stratification, prognostic evaluation and therapeutic decision making. How to reduce early mortality and thus improve overall survival, how to implement appropriate supportive treatment to reduce treatment-associated complications, and how to reduce treatment-related mortality are the key to the improvement of therapies for childhood acute myeloid leukemia.
Child ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; mortality ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics

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*

OBJECTIVETo explore clinical and experimental features of 28 cases of childhood acute myeloid leukemia (AML) with 11q23/MLL gene rearrangements.

METHODSKaryotypes of 234 cases of de novo childhood AML were analyzed using short-term culture of bone marrow cells and R-banding. The fusion transcripts involving MLL gene and partial tandem duplication of MLL (MLL-PTD) were detected by multiple reverse transcription polymerase chain reaction (RT-PCR) assay. Two cases with 11q23 translocation by karyotypic analysis but with negative result of multiple RT-PCR were studied with MLL-dual-color fluorescence in situ hybridization (D-FISH).

RESULTSR-banding karyotypic analysis has revealed 20 cases with 11q23 translocation (14 cases with M5, 4 cases with M4, 2 cases with M2), including 12 cases with t(9;11)(p22;q23), 3 cases with t(1;11)(q21;q23), 2 cases with t(6;11)(q27;q23), 1 case with t(11;19)(q23;p13), 1 with t(5;11)(q31;q23), and 1 with t(X;11)(q24;q23). Eighteen cases with 11q23 translocation having fusion transcripts involving MLL genes were confirmed with multiple RT-PCR; 2 cases showed negative results, but they were confirmed to have MLL rearrangements by D-FISH. MLL-PTD was also detected in 8 cases (4 cases M5, 2 cases M4, M2 and M6, one case each) from the other childhood AML cases. The total incidence of 11q23/MLL gene rearrangements was 11.97% (28/234), and most of patients(85.7%, 24/28) were M4/M5. The complete remission (CR) rate after treatment for the 28 cases with MLL rearrangements was 53.8%, the difference was significant by statistics (P< 0.05) compared with 90.5% for the control group (M4/M5 childhood AML with other karyotypic abnormalities or normal karyotype). Of them, 2 cases receiving intensive chemotherapy survived for 81 and 66 months, respectively, 4 cases receiving allogeneic stem cell transplantation survived for 21, 20, 16 and 11 months, respectively, and are still alive with CR. The medium survival (MS) time for 28 cases with 11q23/MLL rearrangements was 11 months, whereas the MS for control group was 15 months. The difference was not statistically significant(P> 0.05).

CONCLUSIONThe 11q23/MLL rearrangements is highly correlated with the occurrence of monocytic leukemia (M4 and M5). The 11q23 translocation and MLL-PTD are mutually exclusive, though both are indicative of poor prognosis. Intensive chemotherapy and allogeneic stem cell transplantation may ameliorate the clinical outcome. Multiple RT-PCR combined with karyotypic analysis and D-FISH are useful for screening the 11q23/MLL rearrangements in childhood AML.

Adolescent ; Child ; Child, Preschool ; Chromosomes, Human, Pair 11 ; Female ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; mortality ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Remission Induction ; Translocation, Genetic ; Treatment Outcome

The purpose of this study was to detect the minimal residual disease (MRD) in peripheral blood of newly diagnosed patients with acute myeloid leukemia (AML) on day 8 of induction chemotherapy and analyze the correlation between day 8 MRD (D8RD) and therapeutic effectiveness. 29 adult patients (13 males and 16 females, aged 16 - 75 years, median 41 years) with AML diagnosed and treated in West China Hospital from September 2009 to June 2010 were analyzed and followed up in the study. The leukemia-associated aberrant immunophenotype (LAIP) of all the patients were detected by multiparameter flow cytometry (FCM) before therapy. The level of MRD in the peripheral blood at day 8 of induction chemotherapy was detected by FCM based on the LAIP. The overall survival curve was drawn by calculation using Kaplan-Meier method using, and the comparison between different groups was carried out by Log-rank test. The results indicated that after first course therapy, the levels of peripheral D8RD in 7 out of 29 AML cases were lower than 0.01% (negative group), and that in another 22 cases were higher than 0.01% (0.08% - 55%, positive group). The sex, age, WBC, LDH, percentage of bone marrow blasts at diagnosis in these groups were not statistically different. 6 cases achieved CR (86%) in D8RD negative group, and also 6 cases achieved CR (27%) in D8RD positive group, CR rate in D8RD negative group was higher than in D8RD positive group (86% vs 27%, P < 0.05). The median follow-up of 29 cases lasted for 15 months; the 1-year overall survival rate of D8RD negative and D8RD positive groups was 100% and 39.4%, respectively (P < 0.01). It is concluded that MRD level in peripheral blood at day 8 of induction chemotherapy is an early index to predict clinical efficacy of induction therapy in AML.
Adolescent ; Adult ; Aged ; Early Diagnosis ; Female ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; blood ; drug therapy ; mortality ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; drug therapy ; mortality ; Prognosis ; Survival Rate ; Treatment Outcome ; Young Adult

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
Adolescent ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy ; Child ; Child, Preschool ; Disease-Free Survival ; Hospitals ; Humans ; Infant ; Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy ; Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy ; Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy ; Osteosarcoma/diagnosis/epidemiology ; Retrospective Studies ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Autologous ; Young Adult

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
Adolescent ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy ; Child ; Child, Preschool ; Disease-Free Survival ; Hospitals ; Humans ; Infant ; Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy ; Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy ; Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy ; Osteosarcoma/diagnosis/epidemiology ; Retrospective Studies ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Autologous ; Young Adult

The overexpression of X-linked inhibitor of apoptosis protein (XIAP), a member of IAP family protein, is intuitively expected to be associated with unfavorable clinical features in malignancies; however, there have been only a very limited number of studies reporting the clinical relevance of XIAP expression. This study was performed to investigate the prognostic relevance of XIAP expression in childhood acute myeloid leukemia (AML). In 53 children with de novo AML, the level of XIAP expression was determined by using quantitative reverse transcriptase-polymerase chain reaction and was analyzed with respect to the clinical characteristics at diagnosis and treatment outcomes. As a result, the XIAP expression was found to be higher in patients with extramedullary disease than in those without (P=0.014). In addition, XIAP overexpression (> or =median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a worse 3-yr relapsefree survival rate (52.7+/-20.9% vs. 85.9+/-14.8%, P=0.014). Multivariate analyses revealed that XIAP overexpression was an independent unfavorable prognostic factor for relapse-free survival (hazard ratio, 6.16; 95% confidence interval, 1.48-25.74; P=0.013). Collectively, XIAP overexpression may be used as an unfavorable prognostic marker in childhood AML.
Adolescent ; Child ; Child, Preschool ; Female ; Gene Expression Regulation, Leukemic ; Humans ; Infant ; Leukemia, Myeloid, Acute/*diagnosis/drug therapy/mortality ; Male ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; X-Linked Inhibitor of Apoptosis Protein/*metabolism

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