James H Feusner

Children's Hospital & Research Center Oakland, Oakland, California, United States

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Publications (90)555.01 Total impact

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    ABSTRACT: Data are limited regarding outcomes of patients treated for relapsed hepatoblastoma. We reviewed enrollment patterns and outcomes of patients with hepatoblastoma on Children's Oncology Group (COG) phase I/II studies. The medical literature was searched for reports of COG phase I/II studies using PUBMED as well as an inventory from the COG publications office searching manuscripts published from 2000 to 2014. Seventy-one patients with relapsed hepatoblastoma were enrolled on 23 separate COG phase I/II studies. Four studies collected α-fetoprotein (AFP) data, but none utilized AFP decline in assessing response. Most studies enrolled few patients with relapsed hepatoblastoma: 7 studies enrolled 1 patient, and another 7 studies enrolled 2 patients each. Only 9 studies enrolled 3 or more patients with relapsed hepatoblastoma. Four responses were reported. Dedicated strata and/or focus on 1 or 2 studies with compelling biological or clinical rationale for hepatoblastoma may improve accrual (and statistical significance of response data) of patients with relapsed hepatoblastoma. Prospective study of AFP decline versus RECIST response could help determine the optimal method of assessing response to identify potentially beneficial treatments in hepatoblastoma.
    No preview · Article · Nov 2015 · Journal of Pediatric Hematology/Oncology
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    ABSTRACT: Background: Multiple randomized trials have demonstrated a benefit for all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). Pseudotumor cerebri (PTC) is an infrequently reported adverse effect of ATRA. Methods: We examined the incidence, clinical course, and outcomes of patients with APL treated on Intergroup Protocol 0129 (I0129) who developed PTC. This trial evaluated the role of ATRA alone during induction and/or as maintenance therapy. Results: Of the patients on trial, 240 received ATRA during induction, maintenance, or both; 8 had a clinical suspicion for PTC. Upon review of individual cases, this was felt to be "probable" in 4 patients, "possible" in 1 and "unlikely" in 3 due to lack of diagnostic criteria or presence of a more likely alternate diagnosis. Conclusions: "Probable" PTC occurred in 1.7% of patients who received ATRA during induction and/or maintenance therapy. In agreement with previous reports, the incidence of PTC in APL patients receiving ATRA was higher in the pediatric population. Here, we discuss the method for diagnosing PTC in the setting of ATRA therapy and management strategies.
    No preview · Article · Nov 2015 · Clinical lymphoma, myeloma & leukemia

  • No preview · Article · Jun 2015
  • Anne Marsh · Anurag K. Agrawal · James H. Feusner
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    ABSTRACT: Tumor lysis syndrome (TLS) is a metabolic complication of rapid cell turnover and therefore is seen most frequently in pediatric oncology patients with large tumor burdens (often with renal parenchymal involvement), tumors with short doubling times and those exquisitely sensitive to cytotoxic therapy such as acute lymphoblastic leukemia (ALL) and non- Hodgkin lymphoma (NHL). TLS can include metabolic complications related to hyperkalemia, hyperphosphatemia (with resultant hypocalcemia) and hyperuricemia. Laboratory TLS (LTLS) should be differentiated from clinical TLS (CTLS); CTLS includes seizures, cardiac arrhythmias and acute kidney injury necessitating renal dialysis. Recognition of risk factors for LTLS and preventive therapy remain the most important management steps to minimize development of CTLS. The evidence basis behind recommendations in the management of TLS is often negligible and therefore based mostly on consensus statements; here we analyze the existing literature in relation to the consensus statements to determine and grade rational guidelines.
    No preview · Article · Jan 2015
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    ABSTRACT: Background Hepatoblastoma is a malignancy of young children. Low birth weight is associated with significantly increased risk of hepatoblastoma and neonatal medical exposures are hypothesized as contributors. This study represents the largest case–control study of hepatoblastoma to date and aimed to define the role of neonatal exposures in hepatoblastoma risk among low birth weight children.ProcedureIncident hepatoblastoma cases who were born <2,500 g (N = 60), diagnosed between 2000 and 2008, were identified through the Children's Oncology Group. Controls were recruited through state birth registries (N = 51). Neonatal medical exposures were abstracted from medical records. Subjects from the Vermont Oxford Network were used for further comparisons, as were existing reports on neonatal medical exposures.ResultsCase–control comparisons were hindered by poor matching within birth weight strata. Cases were smaller and received more aggressive neonatal treatment compared to controls, and reflected high correlation levels between birth weight and treatments. Similar difficulty was encountered when comparing cases to Vermont Oxford Network subjects; cases were smaller and required more aggressive neonatal therapy. Furthermore, it appears hepatoblastoma cases were exposed to a greater number of diagnostic X-rays than in case series previously reported in the neonatal literature.Conclusions This study presents the largest case series of hepatoblastoma in <2,500 g birth weight infants with accompanying neonatal medical exposure data. Findings confirm that birth weight is highly correlated with exposure intensity, and neonatal exposures are themselves highly correlated, which hampers the identification of a causal exposure among hepatoblastoma cases. Experimental models or genetic susceptibility testing may be more revealing of etiology. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    No preview · Article · Nov 2014 · Pediatric Blood & Cancer
  • Ana Aguilar · Anurag K. Agrawal · James H. Feusner

    No preview · Chapter · Oct 2014
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    ABSTRACT: Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning > 60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to > 50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed.
    Full-text · Article · Sep 2014 · Blood Reviews
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    ABSTRACT: Acute myeloid leukemia is classified based upon recurrent cytogenetic abnormalities. The t(15;17)(q24.1;q21.1) abnormality is found in 5% to 8% of de novo acute myeloid leukemia and is diagnostic of acute promyelocytic leukemia (APL). The translocation results in fusion of the retinoic acid receptor-α (RARA) gene at 17q21.1 and the promyelocytic leukemia (PML) gene at 15q24.1. Standard APL therapy is a combination of all-trans retinoic acid and anthracycline-based chemotherapy. Anthracycline treatment is associated with secondary clonal chromosomal aberrations that can lead to therapy-related secondary myeloid neoplasms. We present a pediatric case of relapsed APL coexistent with treatment-associated secondary myeloid neoplasm with t(11;19)(q23;p13.1).
    Full-text · Article · Jun 2014 · Journal of Pediatric Hematology/Oncology
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    ABSTRACT: Patients with Beckwith-Wiedemann Syndrome (BWS) are predisposed to developing hepatoblastoma. Clinical data were reviewed in all cases of hepatoblastoma in patients with BWS reported in the literature and from personal cases. Patients were identified by literature review using PubMed and by a search of the authors' local tumor registries. Fifty-six patients were identified. The median age of presentation with hepatoblastoma was 6 months (range birth-30 mo). Thirteen of 26 patients were born prematurely. Of 31 evaluable patients, 19 exhibited hemihypertrophy. Thirty-two of 33 patients with α-fetoprotein data reported had elevated levels at diagnosis. Overall survival was 75% (27 of 36 patients). Of 25 patients with data who survived, 24 were treated with chemotherapy and surgery (vs. only 2 of 8 who did not survive). All 9 patients with hepatoblastoma detected by routine screening with outcomes reported were surviving at the time of the reports. Overall survival was high in patients with BWS and hepatoblastoma, especially given lower stage at presentation and when treated with surgery and chemotherapy. Future prospective trials should evaluate if BWS is independently associated with outcome and if the outcome is improved by routine screening.
    No preview · Article · Mar 2014 · Journal of Pediatric Hematology/Oncology
  • Matthew A Kutny · John Gregory · James H Feusner
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    ABSTRACT: Acute promyelocytic leukaemia (APL) in children and adolescents shares many features with APL in adults. There are important distinctions, however, between these age groups in the presentation, complications and treatment outcomes. Paediatric patients are more likely to present with high risk features including elevated WBC count or microgranular variant (M3v). Yet the early death rate is lower in paediatric patients compared to adult patients. Overall outcomes such as CR, OS and EFS appear similar in paediatric and adult patients treated on similar regimens except that very young children may have a higher risk of relapse. While contemporary studies have clearly demonstrated improved survival in adults receiving ATO therapy, currently there is more limited data on the role of ATO in paediatric patients. Here we highlight the similarities and important distinctions between paediatric and adult APL while reviewing available data on treatment of paediatric APL.
    No preview · Article · Mar 2014 · Bailli&egrave re s Best Practice and Research in Clinical Haematology
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    ABSTRACT: Children with high-risk or relapsed hepatoblastoma continue to represent treatment challenges. Multiple case reports have documented the use of high-dose chemotherapy with stem cell rescue (HDC) for this population; however, the efficacy and appropriate use of HDC remains unclear. A literature search was performed to identify cases of hepatoblastoma that were treated with HDC. Additional patients were identified by a query through the Pediatric Blood and Marrow Transplant Consortium. All cases were categorized as undergoing HDC as part of their initial treatment or for relapsed disease. Overall survival (OS) and event-free survival (EFS) proportions were calculated for each group. Subgroup analyses were performed looking at the effects of remission status, initial stage, and relapse site. Forty-two patients were identified. Thirty-one patients received HDC as part of their initial treatment and 55% were long-term survivors with 48% event-free. Eleven received HDC for relapsed disease and 64% were long-term survivors, 36% without events. It is difficult to draw firm conclusions from a small number of nonrandomized patients who had different stages, treatments, and events before undergoing HDC. However, our calculated EFS and OS proportions are consistent with current data using multimodal therapy without HDC, suggesting that HDC (at least as currently delivered) for hepatoblastoma may not be beneficial.
    No preview · Article · Feb 2014 · Journal of Pediatric Hematology/Oncology
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    ABSTRACT: Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy. Pediatr Blood Cancer 2013;9999:1-9. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Nov 2013 · Pediatric Blood & Cancer
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    ABSTRACT: Background: Anthracycline agents are used for treatment of acute myeloid leukemia (AML) but may cause late-onset cardiomyopathy. Current frontline therapy for AML in North America, as reflected in the approach of the Children's Oncology Group (COG) and other pediatric consortia, is adapted from the anthracyline-intensive Medical Research Council (MRC) regimen. The purpose of this study was to describe early post-treatment cardiac function as a potential indicator of acute and long-term risk associated with this approach. Procedure: A multi-center retrospective cohort analysis was conducted of AML survivors diagnosed from 2004 to 2009 and treated with MRC-based regimens. Change in left ventricular shortening fraction (LVSF) on echocardiogram was determined from baseline to latest post-treatment/pre-relapse value; associations with potential predictors were examined. Results: This cohort of pediatric survivors (n = 52) was assessed at a median interval of 13 months from end of treatment. Mean cumulative anthracycline dose was 339 ± 14 mg/m(2) . Mean baseline and post-treatment LVSF were 39.3 ± 0.8% and 35.4 ± 0.9%, respectively; mean percent change for individuals was -8.4 ± 2.8% (P < 0.001). Cardiac-directed medications were initiated in four patients (7.7%). Decline in LVSF was significantly associated with cumulative anthracycline dose, increasing BMI and Hispanic ethnicity. Conclusion: Early, significant decline in LVSF was observed following treatment with these MRC-based regimens. Elevated BMI and Hispanic ethnicity were identified as new independent risk factors. Children and adolescents so treated are at substantial risk for late-onset cardiomyopathy, require monitoring with annual echocardiogram per current COG survivorship guidelines, and are good candidates for appropriate cardioprotection strategies.
    No preview · Article · Sep 2013 · Pediatric Blood & Cancer
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    ABSTRACT: Background. Hepatoblastoma (HB) is a rare pediatric liver tumor that has significantly increased in incidence over the last several decades. The International Agency for Cancer Research (IARC) recently classified HB as a tobacco-related cancer. Parental alcohol use has shown no association. We examined associations between parental tobacco and alcohol use around the time of pregnancy and HB in a large case-control study. Methods. Maternal interviews were completed for 383 cases diagnosed in the U.S. during 2000-2008. Controls (n=387) were identified through U.S. birth registries and frequency-matched to cases on birth weight, birth year, and region of residence. We employed unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between parental smoking and maternal drinking and offspring HB. Results. We found no association between HB and maternal smoking at any time (OR=1.0; 95% CI=0.7-1.4), within the year before pregnancy (OR=1.1; 95% CI=0.8-1.6), early in pregnancy (OR=1.0; 95% CI=0.7-1.6), or throughout pregnancy (OR=0.9; 95% CI=0.5-1.6). We observed marginally positive associations between HB and paternal smoking in the year before pregnancy (OR=1.4; 95% CI=1.0-2.0) and during pregnancy (OR=1.4; 95% CI=0.9-2.0). Maternal alcohol use was not associated with HB. Conclusion. Our results do not provide evidence for an etiological relationship between maternal smoking or drinking and HB, and only weak evidence for an association for paternal smoking in the year before pregnancy. Impact. Our study provides limited support for HB as a tobacco-related cancer; however, it remains wise to counsel prospective parents on the merits of smoking cessation.
    No preview · Article · Aug 2013 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: We report a long-term follow-up (median 11.8 years) of the First North American Intergroup Study. 379 patients were randomized to induction with ATRA or to chemotherapy. All complete responders (CR) received consolidation chemotherapy, then randomized to 1 year ATRA or observation. 245 patients received ATRA sometime during the study: 195 (80%) achieved a CR. Nine (4.6%) relapsed late (>3 years from CR), the last occurred after 4.6 years; 7 of them were still alive after 5.5-15 years. In APL patients, late relapses are uncommon, and those who sustain CR >5 years can be considered cured.
    No preview · Article · Mar 2013 · Leukemia research
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    ABSTRACT: Background: Hepatoblastoma is a rare childhood liver cancer with an obscure etiology, however it is potentially associated with selected pregnancy events and hepatoblastoma risk in offspring. Methods: Adjusted unconditional logistic regression estimated odds ratios (OR) and corresponding 95% confidence intervals (CI) for self-reported pregnancy events and medication use in a sample of mothers of 383 childhood hepatoblastoma cases and 387 controls. Results: Risk of hepatoblastoma was significantly associated with maternal first trimester weight gain (OR = 1.02; 95% CI 1.00, 1.04 per 1 lb increase and nearly significantly with maternal multivitamin use (OR = 0.73; 95% CI 0.51, 1.03). Hepatoblastoma was not associated with other maternal weight changes, maternal illness or medication use during pregnancy. Conclusion: We found little evidence that maternal illness or most medication use during pregnancy are associated with hepatoblastoma in offspring.
    No preview · Article · Jan 2013
  • Angela D Trobaugh-Lotrario · James H Feusner
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    ABSTRACT: Successful treatment of recurrent hepatoblastoma (HB) relies largely on surgical resection. When tumors are responsive, chemotherapy can be used to render patients resectable. Various chemotherapeutic regimens studied in small numbers of patients on phase I/II trials have shown few responses. The best available data indicate that doxorubicin, if not given during intial treatment, and irinotecan are the most active agents in recurrent HB. Stem cell transplantation and radiation therapy have been reported in several patients with unclear successes. Advances in therapy for relapsed patients require concentrating enrollment in one or two phase I/II trials utilizing agents with promising preclinical data. Pediatr Blood Cancer 2012; 59: 813-817. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Nov 2012 · Pediatric Blood & Cancer
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    ABSTRACT: The past four decades has brought significant improvement to the diagnosis, treatment, and outcomes of children diagnosed with hepatoblastoma. These improvements are the results of multidisciplinary and multi-institutional international cooperative trials, such as those conducted by the Children's Oncology Group (COG) or the International Childhood Liver Tumor Strategy Group (SIOPEL) and national studies such as those conducted in Germany and Japan. Due to the different treatment strategies used by the various groups, the information generated has been at times complementary but at other times contradictory. In this manuscript, we will provide a global picture of where "we stand and where we are going" in regards to clinical research of childhood hepatoblastoma. We will focus on lessons learned, especially in reference to the experiences of the COG and SIOPEL study groups, and discuss future challenges. Pediatr Blood Cancer 2012; 59: 818-821. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Nov 2012 · Pediatric Blood & Cancer
  • Anne M Marsh · Louise Lo · Ronald A Cohen · James H Feusner
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    ABSTRACT: We report the use of sorafenib and bevacizumab in combination for a patient with recurrent metastatic hepatoblastoma (HB). This combination demonstrated activity against our patient's refractory HB that had been extensively treated with multiple prior chemotherapeutic regimens. The patient had stabilization of radiographic disease coupled with an 83% decrease in his alpha-fetoprotein level. Given the response in this setting and the paucity of other available options, consideration could be given to using this combination as therapy in patients with recurrent HB who have failed more traditional agents. Pediatr Blood Cancer 2012; 59: 939-940. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Nov 2012 · Pediatric Blood & Cancer
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    ABSTRACT: FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL). Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n = 50). Forty-two of the 104 patients (40%) had either FLT3/ITD (n = 28, 27%) or FLT3/ALM (n = 15, 14%). Median diagnostic WBC count was 23,400 cells/µl vs. 3,600 cells/µl for those with and without FLT3/Mut (P < 0.001), and similar results for the cohort of 50 patients treated on C9710 (P < 0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P = 0.004), microgranular variant histology (P = 0.035), and a lower remission rate (P = 0.009). In patients who received ATRA (C9710 or CCG-2911, n = 8), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P = 0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WT patients (47% vs. 0%, P = 0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy. FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease.
    No preview · Article · Oct 2012 · Pediatric Blood & Cancer

Publication Stats

4k Citations
555.01 Total Impact Points


  • 2001-2015
    • Children's Hospital & Research Center Oakland
      Oakland, California, United States
  • 2010-2013
    • Children's Hospital Oakland Research Institute
      Oakland, California, United States
  • 2006
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 2004
    • City of Hope National Medical Center
      • Department of Population Sciences
      Дуарте, California, United States
    • The Children's Hospital of Philadelphia
      • Division of Oncology
      Philadelphia, Pennsylvania, United States
  • 2002
    • University of California, San Francisco
      San Francisco, California, United States
  • 2000
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States