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CEBPa: mutations have been described in adult acute myeloid leukemia (AML) and conferred a favorable prognosis. However, CEBPamutation has not been reported in children. We investigated 117 children with de novo AML using DNA PCR assay followed by sequencing for each PCR product. CEBPamutations were detected in seven patients, four had FAB M2, two M1 and one M4. CEBPamutations only occurred in patients with intermediate cytogenetics and not in 56 children with AML1-ETO, CBFß-MYH11, PML-RARaor MLL rearrangements. Five patients had mutations occurred in both N-terminal part and basic-leucine zipper (bZIP) domain, one had an N-terminal frameshift mutation and the remaining one had an inframe insertion in the bZIP domain. Cloning analysis on five samples carrying more than one mutations demonstrated one homozygous combined mutations and four heterozygous biallelic mutations. Four of seven CEBPamutation(+) patients had cooperating mutations with FLT3-ITD or N-ras mutations compared to 27 in 109 CEBPamutation(-) patients. Our results showed that CEBPamutations occurred in 6%of childhood AML and most exhibited combined mutations in both N-terminal part and bZIP domain.Leukemia (2005) 19, 410-414. doi:10.1038/sj.leu.2403608 Published online 23 December 2004 [ABSTRACT FROM AUTHOR]

The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count <10 x 10(9)/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count <50 x 10(9)/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1%, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide. [ABSTRACT FROM AUTHOR]

A case beta-thalassaemia major complicated with Klebsiella pneumoniae endogenous endophthalmitis is presented to increase physician awareness of the association of the two clinical conditions. Severe morbidity including subretinal abscess and retinal detachment may develop despite aggressive intravenous and intravitreal ceftriaxone therapy, along with vitrectomy and external drainage. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae has been emerging as the leading cause of liver abscess in diabetic patients. Results of molecular typing of K. pneumoniae isolates from two siblings with liver abscess, their family members, and the environment suggest a possibility of cross infection of liver abscess by the fecal-oral route within diabetic patients.

Langerhans cell histiocytosis (LCH) is an enigmatic disease usually occurring in children. Tumor lysis syndrome (TLS) is a clinical syndrome associated with severe metabolic derangement and oliguric acute renal failure. In this report, we present the clinical course of an infant with advanced LCH who had TLS develop after chemotherapy. Treatment with continuous arteriovenous hemofiltration resulted in effective control of serum uric acid, potassium, creatinine, phosphorus, and blood urea nitrogen levels in the blood.

Background: To evaluate T helper 1 (Th1)/Th2 cells and cytokines in patients with three different subtypes of juvenile rheumatoid arthritis (JRA)., Methods: Peripheral blood was obtained from 25 children with JRA suffering from active arthritis (8 systemic, 9 pauciarticular and 8 polyarticular). Eight healthy children were recruited as controls. T helper cells from peripheral blood mononuclear cells (PBMC) were evaluated by using intracellular staining analysis of cytokine production with 3-colored flow cytometry. A Th1 cell was defined as an interferon-gamma (IFN-gamma) producing CD4+ cell, and a Th2 cell as an interleukin-4 (IL-4) producing CD4+ cell. The production of IL-2, IL-4, IL-5 and IFN-gamma from PBMC was measured by ELISA., Results: In comparison with normal controls, the patients with JRA had significantly fewer Th2 cells among their PBMC (0.78 +/- 0.56% vs. 5.44 +/- 2.33%, p < 0.001). The percentage of Th1 cells among PBMC was not different between patients and normal controls (4.32 +/- 3.24% vs. 4.52 +/- 2.56%, p > 0.5). The ratio of Th1/Th2 cells in the patient group was significantly higher than the control group (8.38 +/- 8.63 vs. 0.95 +/- 0.66, p < 0.001). After 24-hour culture, the PBMC from JRA patients produced less IL-4 than that of controls (3.61 +/- 0.56 pg/mL vs. 4.29 +/- 0.68 pg/mL, p = 0.002). The production of IL-2, IL-5, and IFN-gamma did not show significant differences between JRA patients and normal controls., Conclusion: Decreased IL-4 producing T-helper cells were identified in all three subtypes of JRA. This implicates that an imbalance of Th sub-populations might be a predominant factor in JRA pathogenesis.

Background: Cytogenetic analyses of leukemic cells can be used to define specific subgroups of leukemia with different prognoses and, thereby, indicate appropriate treatment for individual cases. In this study, we investigated the cytogenetic pattern of childhood leukemia in Taiwanese patients., Methods: A modified trypsin method of Seabright was used for G-banding of metaphase cells., Results: From October 1996 to January 1999, 111 children with a diagnosis of leukemia were enrolled in the study. Of these, 73 patients had a diagnosis of acute lymphoblastic leukemia (ALL) and 63 of these patients had successful karyotyping of their leukemic cells. Among them, 20 (30.3%) had a normal karyotype, five had hypodiploidy (all had 45 chromosomes), five had low hyperdiploidy (47-50 chromosomes), 16 (24.2%) had high hyperdiploidy (> 50 chromosomes), and 20 had pseudodiploidy. Chromosomal translocation was identified in 24 (36.4%) of the ALL patients, 17 of whom had recurrent translocations including 10 with CD10+ B-precursor ALL [4 with t(9;22), 5 with t(1;19), and 1 infant with t(8;14)(q24;q11)], one neonate with CD10- early pre-B ALL with t(4;11), three B-cell cases with t(8;14), and three T-cell cases [2 with t(11;19)(q23;p13), and 1 (11;14)(p13;q11)]. One B-precursor patient had dic (9;12). Karyotypes of the 30 patients with acute myeloid leukemia (AML) included eight with t(8;21); seven with the French-American-British-M2 subtype (FAB-M2) and one with M1. All four of the patients with M3 had t(15;17), one patient with M4 had inv(16) and 7q-, one with M4Eo (M4 with eosinophilia) had t(7;16)(q21;q22), one with M0 had t(4;11)(q21;q23), and the remaining 11 had a normal karyotype. Three of the five adult-type chronic myeloid leukemia patients had standard Philadelphia chromosome, and the other two had a variant-form of Philadelphia chromosome. Both of the patients with juvenile myelomonocytic leukemia and one patient with myelodysplastic syndrome had a normal karyotype., Conclusions: Most findings were similar to previous reports. Although the high proportion of FAB-M2 patients (7/8) with t(8;21) and the consequently higher frequency (26.7%) of this translocation in the 30 AML cases in this study might have significance, a larger series of cases is needed to establish this finding.

Background/purpose: Screening programs using urinary vanillylmandelic acid have detected neuroblastomas in early infancy with some success. With the widespread use of ultrasonography in modern obstetric practice, use of ultrasonography to screen for fetal neuroblastoma seems to be reasonable and practical., Methods: Seven fetuses had suprarenal masses detected by maternal ultrasound scan at 32 to 37 weeks' gestation between 1993 and 1998. They were delivered normally if the pregnancy was uncomplicated, especially if it was without maternal preeclampsia or fetal hydrops. Each mass was further confirmed by ultrasound scan, computed tomography, or magnetic resonance imaging in the neonatal period. Tumor excision was performed at the age of 6 to 38 days of life., Results: The size of the masses measured ranged from 2.0x2.0 cm to 4.5x4.5 cm. The diagnosis was adrenal hemorrhage in 1 neonate, Evan's stage I neuroblastoma in 3, and stage IV-S neuroblastoma in 3. All of the specimens with a diagnosis of neuroblastoma showed a favorable histology by the Shimada classification system. Infants with stage I disease were treated with tumor excision only, and they had survived without disease by 14, 18, and 25 months of follow-up. One infant with stage IV-S neuroblastoma was treated further with minimal chemotherapy and has survived without disease at the 66-month follow-up examination. Another child with stage IV-S neuroblastoma has survived with local recurrence and increasing liver metastasis and was still on chemotherapy at the 2-month follow-up examination. The third child with stage IV-S disease presented with massive hepatomegaly and bone marrow involvement, and disseminated intravascular coagulopathy had developed. The patient died on the 5th day of life without surgical intervention., Conclusions: The increasing use of obstetric ultrasonography has made the prenatal screening of neuroblastomas possible. The prognosis of infants with a suprarenal mass may be improved with this early detection and early surgical intervention.

The long-term effects of childhood cancer and its therapy are serious problems that deserve attention. One of the most important late effects is the development of secondary malignancy. We encountered a girl with neuroblastoma who developed acute monoblastic leukemia as a secondary malignancy, 32 months after starting treatment for the primary tumor at the age of 4 years and 10 months. For the primary tumor, she had received cyclophosphamide, ifosphamide, etoposide, epirubicin, cisplatin, and vincristine during a period of 20 months; no radiotherapy was given. Cytogenetic analysis of the leukemic cells showed no specific changes, but a rearrangement of the mixed lineage leukemia gene (chromosome 11q23 translocation) was subsequently found by reverse transcription polymerase chain reaction. The survival time after onset of the secondary malignancy was brief. The leukemogenic hazards of cancer treatment should be weighed against their therapeutic benefits.

Burkitt's lymphoma, the most common childhood non-Hodgkin's lymphoma, usually presents with abdominal tumors. Central nervous system (CNS) involvement in Burkitt's lymphoma is mostly secondary to advanced systemic disease, rarely with brain parenchymal lesions, and was previously recalcitrant to treatment. We report an unusual case of CNS Burkitt's lymphoma with minimal extraneural disease. This 10-year-old immunocompetent boy presented with increased intracranial pressure and seizures and was found to have multifocal intracerebral lesions on brain imaging studies. Cerebrospinal fluid studies confirmed the presence of Burkitt's lymphoma cells. Abdominal computed tomography showed bilateral nephromegaly with left intrarenal lesions that disappeared after three doses of intravenous dexamethasone. The patient was treated for 6.5 months according to the LMB 89 group C protocol of the French Pediatric Oncology Society. The response was brisk and complete. The patient has been disease free for more than 4 years, and is believed to be cured.

Purpose: Subcutaneous panniculitic T-cell lymphoma is reported in a child with idiopathic myelofibrosis. Both disease entities are rarely seen in children., Patient and Methods: A girl aged 5 years and 9 months had pancytopenia and severe constitutional symptoms. Idiopathic myelofibrosis was subsequently diagnosed., Results: A transient response was achieved after treatment with a course of high-dose methylprednisolone therapy. However, proptosis and skin nodules developed during tapering of steroid therapy. A computed tomography scan of the orbit also revealed a mass lesion in the right lacrimal gland region. A skin biopsy specimen showed a subcutaneous panniculitic T-cell lymphoma. The clinical course was marked by high fever, profound pancytopenia, massive gastrointestinal bleeding, and severe, recurrent infections. Her condition rapidly deteriorated, and she died from polymicrobial sepsis 4 months after her initial examination., Conclusions: Subcutaneous panniculitic T-cell lymphoma is a distinctive clinicopathologic entity that is rarely seen in children. The association of myelofibrosis and peripheral T-cell lymphoma as seen in this has been rarely reported.

We report the simultaneous development of fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia in a child treated with sulphasalazine. A 12-year-old girl with juvenile rheumatoid arthritis developed fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia, which was confirmed by liver histology and bone marrow examination, 2 weeks after initiation of sulphasalazine therapy. The patient recovered after administration of high doses of intravenous immunoglobulin. This is the first reported case of the concurrent development of these complications associated with sulphasalazine hypersensitivity. The use of intravenous immunoglobulin may have helped in the treatment of this rare adverse effect of sulphasalazine.

A 15-month-old boy was well except for asymptomatic, erythematous, wheal-like papuloplaques, macules, and nodules on his face and four extremities. It was misdiagnosed by a pediatrician and treated as urticaria for six months. Later, he was sent to our hospital for evaluation of prolonged fever. Acute nonlymphocytic leukemia (M5) with leukemia cutis was diagnosed by results of hematologic examination and examination of a skin biopsy specimen. After one course of chemotherapy, all of the skin lesions completely resolved and had not recurred. Five months after acute nonlymphocytic leukemia was diagnosed, bone marrow relapse and central nervous system involvement were noted.

Sublytic levels (microM) of hemin destabilized RBC membrane as indicated by ghost fragmentation pattern using a laser viscodiffractometer. Furthermore, electron microscopic study shows that 5 microM of hemin induced echinocytic transformation whereas higher hemin concentration (40 microM) induced spherocytic transformation. In addition, hemin oxidized sulfhydryl groups in a dose dependent fashion and Electron Spin Resonance study suggests that such oxidation may involve a thiyl radical. Moreover, sulfhydryl compounds enhanced hemin-induced lipid peroxidation. Desferroxamine could prevent hemin-induced sulfhydryl oxidation as well as hemin-induced decrease in membrane stability. In contrast, vitamin E could effectively prevent hemin-induced lipid peroxidation but could not prevent hemin-mediated membrane destabilization.