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Chicago Ridge, IL, United States

Salloum R.,Burnet Institute | DeWire M.,Burnet Institute | Lane A.,Burnet Institute | Goldman S.,Oncology and Stem Cell Transplant | And 7 more authors.
Journal of Neuro-Oncology

There is a paucity of data regarding patterns of progression in children with high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) treated with bevacizumab (BVZ) at diagnosis. We performed a retrospective study of 20 children with HGG or DIPG who received BVZ-based therapy at diagnosis on, or according to, a bi-institutional study. Magnetic resonance imaging (MRI) characteristics of first and most recent progressions were reviewed. Comparison was made to a control group of 19 patients who never received BVZ. Imaging definitions of progressive disease (PD) were local: at primary site or within 2 cm, contiguous; diffuse: >2 cm away but contiguous with primary site, ill-defined and infiltrative; distant: new, non-contiguous disease. In the BVZ-treated group, 14 patients had DIPG, six patients had HGG. Median age was 7 years (range: 3–21). Median time to PD and follow-up were 8.8 months (range 4–21) and 11 months (range: 6–25), respectively. Among 14 patients with PD, 8 (57.1 %) had local PD, 6 (42.9 %) had local and diffuse/distant PD, at initial progression. At most recent progression, a median of 10.8 months (range 6-25) from diagnosis, 10 of 14 (71.4 %) had at least diffuse (n = 8), or distant (n = 6) PD. In the comparable control group, 15 patients had PD: 11(73.3 %) local, 4 (26.7 %) local and diffuse/distant PD at first and most recent progressions. Based on these data, we postulate that BVZ may lead to a higher incidence of distant and diffuse disease in newly-diagnosed children with HGG or DIPG who received BVZ-based therapy. © 2014, Springer Science+Business Media New York. Source

Liem R.I.,Oncology and Stem Cell Transplant | Kraut M.A.,Johns Hopkins Hospital | Strouse J.J.,Johns Hopkins Hospital | Ball W.S.,Cincinnati Childrens Hospital Medical Center | DeBaun M.R.,Vanderbilt University
Journal of Child Neurology

Detecting silent cerebral infarcts on magnetic resonance images (MRIs) in children with sickle cell anemia is challenging, yet reproducibility of readings has not been examined in this population. We evaluated consensus rating, inter-, and intra-grader agreement associated with detecting silent cerebral infarct on screening MRI in the Silent Infarct Transfusion Trial. Three neuroradiologists provided consensus decisions for 1073 MRIs. A random sample of 53 scans was reanalyzed in blinded fashion. Agreement between first and second consensus ratings was substantial (κ = 0.70, P < .0001), as was overall intergrader agreement (κ = 0.76, P < .0001). In the test-retest sample, intragrader agreement ranged from k of 0.57 to 0.76. Consensus decisions were more concordant when MRIs contained more than one larger lesions. Routine use of MRI to screen for silent cerebral infarcts in the research setting is reproducible in sickle cell anemia and agreement among neuroradiologists is sufficient. © The Author(s) 2013. Source

Olsson R.F.,Karolinska Institutet | Olsson R.F.,Uppsala University | Logan B.R.,Medical College of Wisconsin | Chaudhury S.,Oncology and Stem Cell Transplant | And 14 more authors.

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 10 8 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells. © 2015 Macmillan Publishers Limited All rights reserved. Source

Roberts D.O.,Vanderbilt University | Covert B.,Vanderbilt University | Rodeghier M.J.,Rodeghier Consultants | Parmar N.,Hospital for Sick Children | And 4 more authors.
Pediatric Blood and Cancer

Background: Few studies have investigated factors influencing participation rates for minority children with a chronic disease in clinical trials. The Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial provides an opportunity to study the impact of demographic and socio-economic factors on randomization in a clinical trial among Black children. Our primary objective was to characterize the factors associated with successful randomization of children with sickle cell disease (SCD) and silent cerebral infarct (SCI) in the SIT Trial after initial consent. Procedure: Differences in socio-economic and demographic variables, family history and disease-related variables were determined between eligible participants who were successfully randomized and those who were not randomized following initial consent. Head of household educational level and family income were examined separately for US versus non-US sites. Results: Of 1,176 children enrolled in the SIT Trial, 1,016 (86%) completed screening. Of 208 (20%) children with qualifying SCI on pre-randomization MRI, 196 (94%) were successfully randomized. There were no differences in socio-economic, demographic, or disease-related variables between children who were or were not randomized. Participants from non-US sites were more likely to be randomized (22% vs. 12%, P=0.011); although, randomization by country was associated with neither head of household education nor family income. Conclusion: In the SIT Trial, acceptance of random allocation was not associated with socio-economic or demographic factors. Although these factors may represent barriers for some participants, they should not bias investigators caring for children with SCD in their approach to recruitment for clinical trial participation. © 2014 Wiley Periodicals, Inc. Source

Pillay Smiley N.,Oncology and Stem Cell Transplant | Alden T.,Ann and Robert H. Lurie Childrens Hospital of Chicago | Fangusaro J.,Oncology and Stem Cell Transplant
Pediatric Blood and Cancer

We present a unique case of radiation necrosis in a child with brain stem low-grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone. © 2016 Wiley Periodicals, Inc. Source

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