Proteasome inhibitor bortezomib prevents proliferation and migration of pulmonary arterial smooth muscle cells.

Pulmonary vascular remodeling is a key pathological process of pulmonary arterial hypertension (PAH), characterized by uncontrolled proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Bortezomib (BTZ) is the first Food and Drug Administration (FDA)-approved proteasome inhibitor for multiple myeloma treatment. Recently, there is emerging evidence showing its effect on reversing PAH, although its mechanisms are not well understood. In this study, anti-proliferative and anti-migratory effects of BTZ on PASMCs were first examined by different inducers such as fetal bovine serum (FBS), angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-BB, while potential mechanisms including cellular reactive oxygen species (ROS) and mitochondrial ROS were then investigated; finally, signal transduction of ERK and Akt was examined. Our results showed that BTZ attenuated FBS-, Ang II- and PDGF-BB-induced proliferation and migration, with associated decreased cellular ROS production and mitochondrial ROS production. In addition, the phosphorylation of ERK and Akt induced by Ang II and PDGF-BB was also inhibited by BTZ treatment. This study indicates that BTZ can prevent proliferation and migration of PASMCs, which are possibly mediated by decreased ROS production and down-regulation of ERK and Akt. Thus, proteasome inhibition can be a novel pharmacological target in the management of PAH.

Early neonatal hypoglycemia in term and late preterm small for gestational age newborns.

BACKGROUND: Neonatal hypoglycemia is a common metabolic occurrence among small for gestational age (SGA) neonates. This study aims to determine the incidence of early neonatal hypoglycemia and confirms the potential risk factors among term and late preterm SGA neonates in a well-baby newborn nursery of a tertiary medical center in Southern Taiwan. METHODS: We performed a retrospective medical record review of term and late preterm SGA (birth weight <10 percentile) neonates, born between January 1, 2012 and December 31, 2020, in the well-baby newborn nursery, of a tertiary medical center in Southern Taiwan. Blood glucose monitoring was routinely performed at 0.5, 1, 2, and 4 h of life. Antenatal and postnatal risk factors were recorded. Mean blood glucose level, age of occurrence, symptomatic hypoglycemia, and need for intravenous glucose treatment of early hypoglycemia in SGA neonates were documented. RESULTS: 690 SGA neonates in the nursery met the criteria and were retrospectively enrolled in the study, 358 of whom (51.80%) were male and 332 (48.10%) female. Of 690 enrolled SGA neonates, 134(19.42%) SGA neonates developed hypoglycemia during a well-baby nursery stay. Among these neonates, 97% of early hypoglycemic episodes occur during the first 2 h of life. The lowest blood glucose level was 46.78 ± 11.13 mg/dL, recorded in the first hour of life. Among the hypoglycemic 134 neonates, 26 (19.40%) neonates had to be transferred from the nursery to the neonatal ward and they required intravenous glucose treatment to achieve euglycemia. 14 (10.40%) neonates had symptomatic hypoglycemia. A multivariate logistic regression analysis revealed that cesarean delivery, small head circumference, small chest circumference, and low 1-min Apgar score were significant risk factors for early hypoglycemia in these neonates. CONCLUSION: Periodic routine blood glucose level monitoring within the first 4 h of life in term and late preterm SGA neonates is required, especially those with cesarean delivery and low Apgar score.

Using the forest plot to compare citation achievements in bibliographic and meta-analysis studies since 2011 using data on PubMed Central: A retrospective study.

BACKGROUND: We saw a steady increase in the number of bibliographic studies published over the years. The reason for this rise is attributed to the better accessibility of bibliographic data and software packages that specialize in bibliographic analyses. Any difference in citation achievements between bibliographic and meta-analysis studies observed so far need to be verified. In this study, we aimed to identify the frequently observed MeSH terms in these 2 types of study and investigate whether the highlighted MeSH terms are strongly associated with one of the study types. METHODS: By searching the PubMed Central database, 5121 articles relevant to bibliometric and meta-analysis studies were downloaded since 2011. Social network analysis was applied to highlight the major MeSH terms of quantitative and statistical methods in these 2 types of studies. MeSH terms were then individually tested for any differences in event counts over the years between study types using odds of 95% confidence intervals for comparison. RESULTS: In these 2 studies, we found that the most productive countries were the United States (19.9%), followed by the United Kingdom (8.8%) and China (8.7%); the most number of articles were published in PLoS One (2.9%), Stat Med (2.5%), and Res Synth (2.4%); and the most frequently observed MeSH terms were statistics and numerical data in bibliographic studies and methods in meta-analysis. Differences were found when compared to the event counts and the citation achievements in these 2 study types. CONCLUSION: The breakthrough was made by developing a dashboard using forest plots to display the difference in event counts. The visualization of the observed MeSH terms could be replicated for future academic pursuits and applications in other disciplines using the odds of 95% confidence intervals.

Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0-18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996-December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008-2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996-2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1-RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008-2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008-2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008-2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents' use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Using the IPcase Index with Inflection Points and the Corresponding Case Numbers to Identify the Impact Hit by COVID-19 in China: An Observation Study.

Coronavirus disease 2019 (COVID-19) occurred in Wuhan and rapidly spread around the world. Assessing the impact of COVID-19 is the first and foremost concern. The inflection point (IP) and the corresponding cumulative number of infected cases (CNICs) are the two viewpoints that should be jointly considered to differentiate the impact of struggling to fight against COVID-19 (SACOVID). The CNIC data were downloaded from the GitHub website on 23 November 2020. The item response theory model (IRT) was proposed to draw the ogive curve for every province/metropolitan city/area in China. The ipcase-index was determined by multiplying the IP days with the corresponding CNICs. The IRT model was parameterized, and the IP days were determined using the absolute advantage coefficient (AAC). The difference in SACOVID was compared using a forest plot. In the observation study, the top three regions hit severely by COVID-19 were Hong Kong, Shanghai, and Hubei, with IPcase indices of 1744, 723, and 698, respectively, and the top three areas with the most aberrant patterns were Yunnan, Sichuan, and Tianjin, with IP days of 5, 51, and 119, respectively. The difference in IP days was determined (χ2 = 5065666, df = 32, p < 0.001) among areas in China. The IRT model with the AAC is recommended to determine the IP days during the COVID-19 pandemic.

Novel Compound Heterozygous Mutations in CRTAP Cause Rare Autosomal Recessive Osteogenesis Imperfecta.

Whole-exome sequencing (WES) has advantages over the traditional molecular test by screening 20,000 genes simultaneously and has become an invaluable tool for genetic diagnosis in clinical practice. Here, we reported a family with a child and a fetus presenting undiagnosed skeletal dysplasia phenotypes, while the parents were asymptomatic. WES was applied to the parents and affected fetus to identify the genetic cause of the phenotypes. We identified novel compound heterozygous mutations consisting of a single-nucleotide variant (SNV) and a large deletion in the CRTAP gene (NM_006371.4:c.1153-3C > G/hg19 chr3:g.32398837_34210906del). Genetic alterations of CRTAP are known to cause osteogenesis imperfecta (OI) in an autosomal recessive manner. Further examination of the proband's elder sibling who was diagnosed as OI after birth found that she shares the inherited compound heterozygous mutations of CRTAP; thus, the findings support the disease-causing role of CRTAP mutations. Through the in vitro molecular test and in silico analysis, the deleterious effects of the splicing-altering SNV in CRTAP (c.1153-3C > G) on gene product were confirmed. Collectively, our WES-based pathogenic variant discovery pipeline identifies the SNVs and copy number variation to delineate the genetic cause on the proband affected with OI. The data not only extend the knowledge of mutation spectrum in patients with skeletal dysplasia but also demonstrate that WES holds great promise for genetic screening of rare diseases in clinical settings.

Thomsen-Friedenreich activation in infants with necrotizing enterocolitis in Taiwan.

BACKGROUND: Thomsen-Friedenreich (T) activation in infants with neonatal necrotizing enterocolitis (NEC) has in some cases led to severe hemolysis after transfusions of plasma-containing blood components, causing some authors to advise routine screening for T activation in all infants with NEC. However, no data are available on the frequency of T activation in infants with NEC in Taiwan. STUDY DESIGN AND METHODS: We retrospectively reviewed the medical records of 43 infants with NEC managed in our hospital from 2000 to 2007. In all cases, Arachis hypogaea lectin was used to test for T activation. RESULTS: Of the 43 infants, 16 infants (37%) had Stage II and 27 (63%) had Stage III NEC. Four infants had trace T activation, two of whom received transfusions with washed red blood cells (RBCs) and two with unwashed RBCs. None had evidence of hemolysis. The overall mortality in this series was 16% (7/43), but none of the four babies with T activation died. CONCLUSION: In this series of Taiwanese infants with NEC, weak T activation was present in only 9% (4/43) of infants, and RBC transfusion did not result in hemolysis, regardless of whether washed or unwashed cells were administered. We considered routine screening for T activation and provision of prepared blood components in infants with NEC in Taiwan might be unnecessary.

Update on thalassemia treatment in Taiwan, including bone marrow transplantation, chelation therapy, and cardiomyopathy treatment effects.

Over the past few decades, Taiwan has seen striking improvements in the life expectancy of its 400 registered beta-thalassemia major (beta-TM) patients due mainly to adequate transfusion regimens and effective iron chelation therapy. Since 1995, Taiwanese citizens have enjoyed universal health care through National Health Insurance (NIH), receiving comprehensive treatment at minimal cost. In 1984, a national program for thalassemia prevention, control, and hematopoietic stem cell transplantation (HSCT) was initiated. Recent data show 1- and 2-year event-free survival rates of 85 and 78%, respectively. Chelation agents like deferoxamine (DFO), deferiprone (L1) and deferasirox (DFRA) are available in Taiwan, and therapy is tailored to individuals based on drug availability and tissue distribution of iron load. Intensive chelation regimens combining L1 and DFO are recommended in patients with cardiac complications, while DFRA has been found to be effective in reducing serum ferritin, with acceptable side effects. Here, we report advances in thalassemia treatment in Taiwan and suggest treatment guidelines.

Long-term treatment results of hepatoblastoma at a single institution in Taiwan.

From 1990 to 2004, there were 23 consecutive patients with hepatoblastoma treated at Mackay Memorial Hospital in Taipei, Taiwan. There were 7 patients of stage I, 3 of stage II, 13 of stage III, and none had stage IV disease. Two siblings had congenital hepatoblastoma and both survived. Two patients were prematurity. Beckwith-Wiedemann syndrome, isosexual precocity, chronic B hepatitis presented in 1 patient each. In addition to surgery, we used cisplatin 90 mg/m/d on day 1 and epirubicin 25 mg/m/d for days 1 to 3 as first-line chemotherapy. Each course was repeated every 3 weeks. Epirubicin was chosen because of its lower cardiotoxicity. Carboplatin/etoposide and vincristine/cyclophosphamide/5-fluorouracil were the second-line chemotherapy for considering cumulative toxicity of first-line chemotherapy. If initial total excision was feasible, postoperative chemotherapy of 4 to 6 courses were given. Three patients died of progressive disease, infection, and relapse 1 each. The median duration of follow-up for 20 survived patients was 94 months. The 5-year event-free and overall survival rates were 73.9%+/-9.2% (SE) and 87%+/-7.0%, respectively. Tumor recurred in 5 patients. The commonest toxicity was febrile neutropenia. There was no cardiotoxicity event. In conclusion, with sequential combination of surgery and chemotherapy, the treatment results for hepatoblastoma were satisfactory as compared with other groups.

Interferon-alpha for alarming hemangiomas in infants: experience of a single institution.

BACKGROUND: Hemangioma is the most common tumor in infancy. 'Alarming hemangiomas' refer to the lesions that potentially impair vital structures or cause life-endangering complications, and which warrant vigorous treatment. Interferon-alpha has been used for alarming hemangiomas at Mackay Memorial Hospital, Taipei, Taiwan, since 1994. METHODS: The records of 21 consecutive infants treated between January 1994 and December 2005 were retrospectively reviewed. The initial dose of interferon-alpha was 50 000 IU/kg per day, which was increased to 100,000 IU/kg per day in the second week of therapy if tolerated. It was tapered depending on response, with total treatment lasting no longer than 12 months. Treatment response was evaluated depending on the size of the lesion and resolution of complications. RESULTS: The duration of therapy ranged from 6 to 12 months. Six patients (29%) had a reduction in mass of > or =25% after 1 month of therapy. Twenty patients (95%) had achieved a decrease in size of 50% by 12 months, and 15 (71%) had total involution of lesions by a median age of 13.5 months (range 7-50 months). Only mild and transient adverse effects were encountered. No neurologic complications occurred. CONCLUSIONS: Interferon-alpha appears to be an effective and well-tolerated treatment for alarming hemangiomas in infancy.

Primary autoimmune neutropenia in children in Taiwan.

BACKGROUND: Autoimmune neutropenia in children is caused by granulocyte-specific autoantibodies. These antibodies react to the patient's own neutrophils but disappear when the neutropenia spontaneously remits. This study reviewed our experience with autoimmune neutropenia in children and investigated possible associations with HLA-DR and HLA-DQ alleles. STUDY DESIGN AND METHODS: From 1993 to 2006, our laboratory received 155 blood samples from children with neutropenia. Of these samples, 55 had granulocyte-specific autoantibodies on the indirect granulocyte immunofluorescence test. As the children had no other disorders associated with neutropenia, they were diagnosed with primary autoimmune neutropenia. HLA-DRB1 and -DQB1 allele typing was performed in 31 cases, and the results were compared with those of 190 normal healthy unrelated Taiwanese controls. RESULTS: The mean ages of onset and resolution of neutropenia were 9.8 months (median, 9.0 months; range, 4-28 months) and 22.5 months (median, 20.0 months; range, 13-44 months), respectively. The male-to-female ratio was 1.2:1. The mean absolute neutrophil count was 190 per microL (standard deviation, 213/microL). Most patients (74%) had antibodies against HNA-1a. Autoimmune neutropenia in children in Taiwan was significantly associated with HLA-DQB1*0503 (odds ratio, 6.48; p = 0.0002; p(c) = 0.003) allele. CONCLUSION: In Taiwan, autoimmune neutropenia in children is associated with HLA-DQB1*0503. The autoantibody in autoimmune neutropenia is most commonly anti-HNA-1a.

Triple intrathecal therapy without cranial irradiation for central nervous system preventive therapy in childhood acute lymphoblastic leukemia.

BACKGROUND: To evaluate the treatment results of central nervous system preventive therapy (CNSP) with triple intrathecal therapy (TIT) alone in children with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively studied a cohort of 59 patients with median follow-up time 50.6 months (range: 27-80 months) at a single institution in Taiwan. Patients with ALL were classified in risk groups at diagnosis. TPOG-ALL-93 protocols and TPOG-ALL-2002 protocols were used. Both protocols were for multicenter studies in Taiwan and contained protocols for standard-risk (SR), high-risk (HR), and very-high-risk (VHR) patients. In this study, we used TIT alone for CNSP. In all ALL patients, methotrexate, hydrocortisone, and cytarabine were given at age-dependent doses. RESULTS: As of October 2006, patients had a 3-year event-free survival and an overall survival 89.4 +/- 4.1% (S.E.) and 93.1 +/- 3.3%, respectively. Under TIT no patients had complications such as seizure, encephalitis, or infection, and no morbidities like those caused by cranial irradiation. In this study, we used TIT alone for CNSP and had no CNS relapse. CONCLUSIONS: In the context of effective systemic therapy, TIT alone appears to be effective CNSP for most patients with ALL.

The development of a novel protocol for the treatment of de novo childhood acute myeloid leukemia in a single institution in Taiwan.

From November 1, 1995 to July 31, 2004, 49 children with de novo acute myeloid leukemia (AML) were treated at our institution. One patient who was treated by a different protocol was excluded. In total, 48 patients with de novo AML were enrolled in this study. Forty-two patients with AML other than acute promyelocytic leukemia (non-APL) were treated consecutively with 2 novel protocols: Mackay Memorial Hospital (MMH)-AML-96, designed as a pilot phase, and Taiwan Pediatric Oncology Group (TPOG)-AML-97A, on the basis of MMH-AML-96 with minor modifications. Six patients with APL were treated consecutively with 2 protocols, TPOG-APL-97 and APL-2001. As of July 31, 2006, the remission rates were 79%, 92%, and 98% after 1, 2, and 3 courses of induction therapy, respectively. The 5-year overall survival was 64%+/-6.9% (SE), and the 5-year event-free survival was 60%+/-7.1%; for non-APL AML, the rates were 62%+/-7.5% and 59%+/-7.6%; for APL, 83+/-15.2 and 67+/-19.3%. Among the factors analyzed, a complete remission achieved after 1 course of induction therapy, lactate dehydrogenase <500 IU/L at diagnosis, patients without invasive fungal infection during chemotherapy, and male sex were associated with a favorable outcome.

Invasive fungal infection in children undergoing chemotherapy for cancer.

BACKGROUND: In children with cancer, invasive fungal infection is a serious complication of anticancer therapy. Successful treatment is a major challenge for clinical oncologists. METHODS: The records of all episodes of invasive fungal infection occurring in children with cancer undergoing chemotherapy at Mackay Memorial Hospital, Taipei between January 1987 and October 2005 were reviewed. The following were documented: general characteristics, clinical presentation, predisposing factors, pathogens, antifungal treatment, association with anticancer therapy and outcome. We endeavoured to preserve renal function by administration of new antifungal agents. Anticancer therapy was given as soon as possible after diagnosis and the dose of chemotherapeutic agents was adjusted as required to prevent unduly prolonged interruption of chemotherapy and minimise the risk of leukaemia relapse. RESULTS: Twenty-six patients with 29 episodes of invasive fungal infection were reviewed. Candida species were the leading pathogens (14/29) followed by Aspergillus species (11/29). In six episodes there was both visceral dissemination and fungaemia. In 23/29 patients, antibiotic therapy preceded fungal infection with a median of 11 days. Three children died from extensive fungal infection and four from progression of malignancy; the remainder survived with a median follow-up of 40 months (range 12-233). The actuarial 12-month survival rate was 87%; in patients with invasive candidiasis and aspergillosis the rates were 75% and 100%, respectively. CONCLUSIONS: In children with cancer, most invasive fungal infections can be treated successfully. Current antifungal prophylaxis should protect patients from fungal infection.

In vitro cell growth stimulated by recombinant human cytokines can help to diagnose transient leukemia in neonates.

BACKGROUND/PURPOSE: In a previous study, we demonstrated that in vitro cell growth stimulated by human placental conditioned medium distinguished between transient leukemia (TL) and congenital acute myeloid leukemia (AML) in neonates. We then sought to determine whether the application can be expanded if in vitro cell growths are stimulated by recombinant human cytokines including granulocyte-macrophage colony-stimulating factor (rhGM-CSF), interleukin-3 (rhIL-3), stem cell factor (rhSCF) and thrombopoietin (rhTPO). METHODS: Eight neonates with features indistinguishable from AML were studied. Seven patients had Down syndrome and the eighth a normal phenotype. Bone marrow or peripheral blood mononuclear cells (MNC) were cultured in the presence of rhGM-CSF+rhIL-3+rhSCF or of rhTPO alone. After incubation, granulocyte-macrophage colony-forming units (CFU-GM)-derived colonies and clusters were scored on an inverted microscope. Colony-forming units-megakaryocyte (CFU-MK)-derived colonies were counted with an in situ CD61 immunostained dish. Liquid suspension cultures of MNC were stimulated by rhGM-CSF and/or rhTPO. RESULTS: CFU-GM-derived colonies and clusters from bone marrow and peripheral blood MNC revealed normal patterns in seven patients. RhTPO-stimulated megakaryocyte colony formation was normal in one patient. Cytospin smears of liquid suspension cultures all showed good myeloid or megakaryocytic maturation consistent with TL rather than AML. One neonate died on the 2nd day of life, but in the seven remaining patients, blasts disappeared from the peripheral blood within 10 months. Among four patients followed long-term, one developed myelodysplastic syndrome at 21 months. This child was given tailored chemotherapy and had a disease-free survival>20 months. CONCLUSION: In vitro cell growth stimulated by recombinant human cytokines can help to diagnose TL in neonates.

Hematopoietic progenitor cells increase remarkably in the peripheral blood of children with infection.

BACKGROUND: Peripheral blood (PB) of children with viral infection had remarkable increase in colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colonies and clusters. The authors sought to investigate the hematopoietic changes in children with infection. METHODS: The CFU-GM-derived colonies and clusters, burst-forming unit-erythroid (BFU-E)-derived colonies, and colony-forming unit-megakaryocyte (CFU-MK)-derived colonies assays and methylcellulose and/or agarose culture of PB were performed in 25 controls and 42 infected patients. Hematopoietic cell assays and cell culture of bone marrow (BM) were performed in 28 controls and 12 infected patients. RESULTS: The PB controls had very few CFU-GM-derived colonies and clusters. The PB of infected children had many more CFU-GM-derived colonies and clusters. In addition, PB of infected children had abundant BFU-E-derived colonies and CFU-MK-derived colonies, whereas, from BM there were no statistical differences in the numbers of CFU-GM-derived colonies and clusters, BFU-E-derived colonies, and CFU-MK-derived colonies between infection group and control group. The numbers of CFU-GM-derived colonies and clusters were greater in PB of bacteria-infected patients than those in PB of non-bacteria-infected patients. CONCLUSIONS: PB of infected children had increased numbers of colonies, especially in the bacteria-infected group.

Deferiprone or deferoxamine vs. combination therapy in patients with beta-thalassemia major: a case study in Taiwan.

Deferiprone (L1) has been recommended as an effective oral chelation therapy for patients with beta-thalassemia major (TM). From 1999 to 2004, 114 patients with TM from five treatment centers were enrolled in this program: iron (Fe) was chelated with L1 in 57 patients, deferoxamine (DFO) in 26, and combined L1/DFO therapy in 31. We found that serum ferritin (SF) was significantly lower in nine patients receiving L1 for more than 5 years (p = 0.04), 22 patients receiving L1 for 1-2 years (p < 0.01) and 31 receiving the combined therapy (p = 0.01), yet significantly higher in those receiving DFO only (p < 0.01). One patient showed transient neutropenia; arthropathy in one patient and gastrointestinal upset in two were noted, with no significant change in alanine aminotransferase (ALT) level. Of 17 patients who were submitted to a liver biopsy, 15 showed no significant change in hepatic fibrosis scores after therapy with L1. None of the 88 patients, including 31 who received the combined therapy, have abandoned oral L1 treatment due to adverse effects. Results of this study proved that L1 or combined therapy with L1 and DFO is effective in reducing SP; incidence of adverse events was low in patients with TM.

Recombinant urate oxidase (rasburicase) for the prevention and treatment of tumor lysis syndrome in patients with hematologic malignancies.

In this multicenter, nonrandomized, open-label clinical trial conducted from July 2003 to July 2004, recombinant urate oxidase (rasburicase) was administered to patients at risk for tumor lysis syndrome before or during the initiation of chemotherapy. Forty-five patients were enrolled, including 18 children (10 with acute lymphoblastic leukemia, 6 with high-grade lymphoma, and 2 with acute myeloid leukemia) and 27 adults (8 with acute lymphoblastic leukemia, 4 with high-grade lymphoma, 9 with multiple myeloma, and 6 with acute myeloid leukemia). The age ranged from 3 to 98 years, with a median age of 7 years in children and 59.3 years in adults. There were 14 males and 4 females in the pediatric group and 18 males and 9 females in the adult group. Rasburicase 0.2 mg/kg was administered intravenously once a day for 2-6 days, for a median of 3 days in children and of 4 days in adults. After 3 days of treatment, the median uric acid levels in the 18 children decreased from 10.5 mg/dl (range 8-18.6) to 0.5 mg/dl (range 0.0-1.7). Similarly, in the 27 adults, the median levels decreased from 10.8 mg/dl (range 8-24.4) to 0.5 mg/dl (range 0.0-1.6). No significant changes were observed in serum potassium, calcium, and phosphorus concentrations. None of the patients required dialysis for acute renal failure. Rasburicase was very well tolerated, with only 1 adult having grade 1 vomiting. We conclude that rasburicase is safe and highly effective for preventing the complications of tumor lysis syndrome in patients with hematologic malignancies.