Peyton Manning Childrens Hospital at St Vincent

Indianapolis, IN, United States

Peyton Manning Childrens Hospital at St Vincent

Indianapolis, IN, United States

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Sorrell A.D.,City of Hope National Medical Center | Alonzo T.A.,University of Southern California | Hilden J.M.,Peyton Manning Childrens Hospital At St Vincent | Gerbing R.B.,Childrens Oncology Group | And 9 more authors.
Cancer | Year: 2012

BACKGROUND: Children who are treated for myeloid leukemia associated with Down syndrome (DS) experience superior survival compared with children who have myeloid leukemia without DS. To maintain excellent outcomes while avoiding toxicity, the Children's Oncology Group (COG) conducted the phase 3 trial COG A2971, the first trial solely designed to provide uniform treatment of myeloid leukemia in North American children with DS. A2971 eliminated 2 induction drugs and 3 months of maintenance therapy from the standard-Timing regimen of dexamethasone, cytarabine, 6-Thioguanine, etoposide, and rubidomycin/daunomycin (DCTER) used in the previous study (Children's Cancer Group [CCG] 2891). METHODS: COG A2971 was a multi-institutional, nonrandomized, clinical trial that enrolled 132 patients who had DS with either acute myeloid leukemia (n = 91) or myelodysplastic syndrome (n = 41). RESULTS: The median follow-up was 4.8 years (range, 0.8-8.6 years), the median age at diagnosis was 1.7 years (range, 0.3-13.6 years), and the median white blood cell count was 6200/μL (range, 900-164,900/μL). The remission rate (92.7% ± 6%) was similar to that reported in the CCG 2891 study (91.3% ± 5%; P =.679). The 5-year event free survival (EFS) rate was 79% ± 7% (vs 77% ± 7% in CCG 2891; P =.589), the disease-free survival (DFS) rate was 89% ± 6% (vs 85% ± 6% in CCG 2891; P =.337), and the overall survival rate was 84% ± 6% (vs 79% ± 7% in CCG 2891; P =.302). Induction day-14 bone marrow response trended toward a more favorable outcome (EFS: P =.12). Age >4 years was an adverse risk factor (5-year EFS rate: 33% ± 38% for children aged >4 years [median, 8.5 years; n = 6] vs 81% ± 7% for children ages 0-4 years [median, 1.7 years; n = 126]; P =.001). CONCLUSIONS: The COG A2971 trial reduced the chemotherapy dose and maintained survival to that achieved by the CCG 2891 trial in children who had myeloid leukemia associated with DS. © 2012 American Cancer Society.


Ullrich C.K.,Dana-Farber Cancer Institute | Ullrich C.K.,Childrens Hospital | Dussel V.,Dana-Farber Cancer Institute | Dussel V.,Childrens Hospital | And 6 more authors.
Blood | Year: 2010

The end-of-life (EOL) experience of children who undergo stem cell transplantation (SCT) may differ from that of other children with cancer. To evaluate perspectives and patterns of EOL care after SCT, we surveyed 141 parents of children who died of cancer (response rate, 64%) and their physicians. Chart review provided additional information. Children for whom SCT was the last cancer therapy (n = 31) were compared with those for whom it was not (n = 110). SCT parents and physicians recognized no realistic chance for cure later than non-SCT peers (both P < .001) and were more likely to have a primary goal of cure at death (parents, P < .001; physicians, P = .02). SCT children were more likely to suffer highly from their last cancer therapy and die in the intensive care unit (both P < .001), with less opportunity for EOL preparation. SCT parents who recognized no realistic chance for cure more than 7 days before death along with the physician were more likely to prepare for EOL, and if their primary goal was to reduce suffering, to achieve this (P < .001). SCT is associated with significant suffering and less opportunity to prepare for EOL. Children and families undergoing SCT may benefit from ongoing discussions regarding prognosis, goals, and opportunities to maximize quality of life. © 2010 by The American Society of Hematology.


Bass J.K.,St Jude Childrens Research Hospital | Knight K.R.,Oregon Health And Science University | Yock T.I.,Massachusetts General Hospital | Chang K.W.,Stanford University | And 2 more authors.
Pediatric Blood and Cancer | Year: 2016

Hearing loss (HL) is common in childhood cancer survivors exposed to platinum chemotherapy and/or cranial radiation and can severely impact quality of life. Early detection and appropriate management can mitigate academic, speech, language, social, and psychological morbidity resulting from hearing deficits. This review is targeted as a resource for providers involved in aftercare of childhood cancers. The goal is to promote early identification of survivors at-risk for HL, appropriate evaluation and interpretation of diagnostic tests, timely referral to an audiologist when indicated, and to increase knowledge of current therapeutic options. © 2016 Wiley Periodicals, Inc.


Pinto N.,University of Chicago | Cipkala D.A.,Peyton Manning Childrens Hospital At St Vincent | Ladd P.E.,Peyton Manning Childrens Hospital At St Vincent | Pu Y.,University of Chicago | Cohn S.L.,University of Chicago
Pediatric Blood and Cancer | Year: 2014

Patients <12 months with favorable biology, metastatic neuroblastoma have >90% overall survival following treatment with chemotherapy and surgery. We report two infants with favorable biology, stage 4 neuroblastoma with refractory disease after standard intermediate-risk chemotherapy and additional retrieval chemotherapy. One patient was treated with six additional cycles of isotretinoin and the other observed. Both remain clinically well with persistent disease but no evidence of tumor progression for 28 and 13 months following completion of cytotoxic treatment. Similar to residual tumor in primary sites, refractory metastatic disease may not portend a poor outcome in patients with favorable biology, intermediate-risk neuroblastoma. Pediatr Blood Cancer 2014;61:1104-1106. © 2013 Wiley Periodicals, Inc.


Soster E.L.,Indiana University | Tucker M.,Peyton Manning Childrens Hospital At St Vincent | Escobar L.F.,Peyton Manning Childrens Hospital At St Vincent | Vance G.H.,Indiana University
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2015

Background: Hydranencephaly is a relatively rare but severe structural brain abnormality that often results in perinatal death. Although several factors including infection and multiple births have been reported to be associated with this birth defect, the underlying etiology is not well understood. Recently, FLVCR2 gene mutations have been implicated in a subset of hydranencephaly cases, following an autosomal recessive pattern of inheritance. Case: We report a male infant with hydranencephaly found to have a previously unreported six amino acid deletion in one copy of the FLVCR2 gene following a pregnancy complicated by poor prenatal care and maternal cocaine use. Although our patient currently presents with developmental delays, he is showing progress and gaining some skills. Conclusion: We discuss the possibility of a synergistic effect between the FLVCR2 genetic mutation and environmental cocaine exposure, creating a susceptible brain, as an explanation for this infant's phenotype. This case demonstrates the potential clinical utility of testing for mutations in FLVCR2 for patients with hydranencephaly after other possible etiologies, such as congenital infection, have been reasonably eliminated. Current literature on FLVCR2 is relatively sparse; identifying additional patients with similar mutations will aid in defining the clinical significance of a gene mutation and the contribution to the etiology of hydranencephaly. © 2014 Wiley Periodicals, Inc.


Johnson K.J.,University of Minnesota | Roesler M.A.,University of Minnesota | Linabery A.M.,University of Minnesota | Hilden J.M.,Peyton Manning Childrens Hospital At St Vincent | And 2 more authors.
Pediatric Blood and Cancer | Year: 2010

Background. Leukemia in infants is rare and has not been well studied apart from leukemia in older children. Differences in survival and the molecular characteristics of leukemia in infants versus older children suggest a distinct etiology, likely involving prenatal factors. Procedure. We examined the association between eight categories of maternally reported congenital abnormalities (CAs) (cleft lip or palate, spina bifida or other spinal defect, large or multiple birthmarks, other chromosomal abnormalities, small head or microcephaly, rib abnormalities, urogenital abnormalities, and other) and infant leukemia in a case-control study. The study included 443 cases diagnosed at <1 year of age at a Children's Oncology Group Institution in the United States or Canada from 1996 to 2006 and 324 controls. Controls were recruited from the cases' geographic area either by random digit dialing (1999-2002) or through birth certificates (2003-2008) and were frequency-matched to cases on birth year. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjustment for birth year and a measure of follow-up time to account for differences in the CA observation period. Results. No statistically significant associations were observed between infant leukemia and any CA (OR=1.2; 95% CI: 0.8-1.9), birthmarks (OR=1.4; 95% CI: 0.7-2.5), urogenital abnormalities (OR=0.7; 95% CI: 0.2-2.0), or other CA (OR=1.4; 95% CI: 0.7-2.8). Results were similar for acute lymphoblastic and myeloid leukemia cases. Fewer than five subjects were in the remaining CA categories precluding analysis. Conclusions. Overall, we did not find evidence to support an association between CAs and infant leukemia. © 2010 Wiley-Liss, Inc.


Kirkpatrick B.E.,St Vincent Womens Hospital | El-Khechen D.,Peyton Manning Childrens Hospital at St Vincent
Clinical Dysmorphology | Year: 2011

We present a 3-year-old female with 22q13 deletion syndrome, 46, XX, del (22) (q13.1)dn.ish del (22) (q13.31) (ARSA-,22qSUBTEL-). The terminal deletion was diagnosed antenatally through amniocentesis after sonographic detection of unilateral multicystic kidney and unilateral cleft lip (Figs 1 and 2), both left-sided. The pregnancy was complicated by polyhydramnios, yet continued to 40 weeks gestation without other complication. The sonographic findings were confirmed after delivery. At 22 months of age, the patient was diagnosed with Wilms tumor of the kidney not affected with cysts. Neither orofacial clefting nor Wilms tumor has been reported earlier in a patient with 22q13 deletion syndrome (also known as PhelanMcDermid syndrome). © 2011 Wolters Kluwer Health. Lippincott Williams & Wilkins.


Lenz A.M.,University of South Florida | Shulman D.,University of South Florida | Eugster E.A.,Indiana University | Rahhal S.,Peyton Manning Childrens Hospital At St Vincent | And 3 more authors.
Pediatrics | Year: 2010

Testotoxicosis, a form of gonadotropin-independent precocious puberty, results from an activating mutation of the luteinizing hormone receptor expressed in testicular Leydig cells. Affected males experience early testosterone secretion, virilization, advancing bone age, and resultant short stature. Recently, the use of combination therapy with a potent antiandrogen agent (bicalutamide) and a third-generation aromatase inhibitor (anastrozole or letrozole) was reported to yield encouraging short-term results. We present here the results of longer-term treatment (4.5 and 5 years) with this combination therapy in 2 boys who demonstrated that it is well tolerated, slows bone-age advancement in the face of continued linear growth, and prevents progression of virilization. Copyright © 2010 by the American Academy of Pediatrics.


Cooper T.M.,Children's Healthcare Of Atlanta | Razzouk B.I.,Peyton Manning Childrens Hospital at St Vincent | Gerbing R.,Childrens Oncology Group | Alonzo T.A.,University of Southern California | And 5 more authors.
Pediatric Blood and Cancer | Year: 2013

Background: The discovery of effective re-induction regimens for children with more than one relapse of acute lymphoblastic leukemia (ALL) remains elusive. The novel nucleoside analog clofarabine exhibits modest single agent efficacy in relapsed ALL, though optimal combinations of this agent with other active chemotherapy drugs have not yet been defined. Herein we report the response rates of relapsed ALL patients treated on Children's Oncology Group study AAML0523, a Phase I/II study of the combination of clofarabine and cytarabine. Procedure: AAML0523 enrolled 21 children with ALL in second or third relapse, or those refractory to re-induction therapy. The study consisted of two phases: a dose finding phase and an efficacy phase. The dose finding portion consisted of a single dose escalation/de-escalation of clofarabine for 5 days in combination with a fixed dose of cytarabine (1g/m2/day for 5 days). Eight patients received clofarabine at 40mg/m2/day and 13 patients at 52mg/m2/day. Results: Toxicities observed at all doses of clofarabine were typical of intensive chemotherapy regimens for leukemia, with infection being the most common. We did not observe significant hepatotoxicity as reported in other clofarabine combination regimens. The recommended pediatric Phase II dose of clofarabine in combination with cytarabine for the efficacy portion of AAML0523 was 52mg/m2. Of 21 patients with ALL, 3 (14%) achieved a complete response (CR). Based on the two-stage design definition of first-stage inactivity, the therapy was deemed ineffective. Conclusion: The combination of clofarabine and cytarabine in relapsed/refractory childhood ALL does not warrant further clinical investigation. © 2013 Wiley Periodicals, Inc.


Valentine M.C.,University of Washington | Linabery A.M.,University of Minnesota | Chasnoff S.,University of Washington | Hughes A.E.O.,University of Washington | And 10 more authors.
Leukemia | Year: 2014

Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. Although most cases are accompanied by MLL rearrangements and harbor very few somatic mutations, less is known about the genetics of the cases without MLL translocations. We performed the largest exome-sequencing study to date on matched non-cancer DNA from pairs of mothers and IL patients to characterize congenital variation that may contribute to early leukemogenesis. Using the COSMIC database to define acute leukemia-associated candidate genes, we find a significant enrichment of rare, potentially functional congenital variation in IL patients compared with randomly selected genes within the same patients and unaffected pediatric controls. IL acute myeloid leukemia (AML) patients had more overall variation than IL acute lymphocytic leukemia (ALL) patients, but less of that variation was inherited from mothers. Of our candidate genes, we found that MLL3 was a compound heterozygote in every infant who developed AML and 50% of infants who developed ALL. These data suggest a model by which known genetic mechanisms for leukemogenesis could be disrupted without an abundance of somatic mutation or chromosomal rearrangements. This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins. © 2014 Macmillan Publishers Limited.

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