bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of myeloablative (MA) autologous stem Cell (Auto SCT) followed by reduced intensity (RI) allogeneic transplantation (AlloSCT) in children with relapsed/refractory(R/R) Hodgkin’s disease (HD)
Authors: Bradley M. , Baldinger L. , Bhatia M. , Garvin J. , George D. , Roman E. , Satwani P. , Martin P. L. , Kurtzberg J. , Cairo M. S. 
Published: March 2020

20007 Background: Allo SCT may benefit patients with R/R HD by providing a graft vs lymphoma effect. Peggs et al (Lancet 2005) demonstrated durable engraftment and reduced non relapse mortality (NRM) in HD pts post RI Allo SCT. Carella et al (JCO2000) and Gutman et al (BMT2005) demonstrated the success of MA Auto SCT followed by RI AlloSCT in adults with refractory lymphoma. We investigated the feasibility of MA Auto SCT followed by RI Allo SCT in children with R/R HD. Methods: MA conditioning prior to AutoSCT was CTX 1,500 mg/m2 x 4 d, BCNU 100 mg/m2 x 3d, VP-16 800 mg/m2 x 3d. AlloSCT conditioning was fludarabine 30 mg/m2 x 5d, busulfan 3.2 mg/kg x 2d, and R ATG 2 mg/kg x 4d (unrel. donor). CD20+ patients received rituximab (375 mg/m2/wk x4) and all pts received involved field radiotherapy (IFRT). Results: Ten pts have enrolled, 2 pts did not proceed (parental withdrawal) to RI AlloSCT (Donors: 1 MRD, 2 MUD, 5 UCB). Median time to RI AlloSCT after MA Auto SCT was 142 d (97–219). The median cell dose was 3.43 x 107 TNC/kg for UCB grafts (n=5). Engraftment was achieved at a median of 20.5 d for PMN and 46.5 d for PLT. Donor chimerism reached ≥ 95% in all pts by day 100 with a median follow up of 703d (128–2025). Toxicities were grade (3) hematuria (n=1), (3–4) infection (n=7), (4) pulmonary fibrosis (n=1), (4) hearing loss (n=1), (4) neurotoxicity (n=1). GVHD: grade II-III aGVHD (3/8), cGVHD (3/8). Six patients are alive and NED post allo SCT. There has been one NRM (cGVHD) and one relapse mortality. The OS at one year is 66.7%. Conclusions: MA AutoSCT followed by RI AlloSCT is feasible and well tolerated in pediatric pts with R/R HD. A larger study with longer follow up is required to determine if this approach will reduce relapse, long term toxicity and/or improve survival. No significant financial relationships to disclose.
Advances in management of childhood acute leukemia (AML, ALL): Experience at a developing country, National Guard hospital, western region of Kingdom of Saudi Arabia
Authors: Khattab T. M. , Atra A. A. , Felimban S. K. , Fryer C. 
Published: March 2020

20020 Background: The outcome of children with acute myeloid leukemia (AML) has improved over last two decades. The main factors behind this are increasing intensity of chemotherapy and improved measures of supportive care. While white blood cell count and age are major factors for risk classification in childhood acute lymphoblastic leukemia (ALL), therapy remains the single most prognostic factor. Objectives: To assess survival with each regimen of chemotherapy and causes of treatment failure. Methods: we retrospectively reviewed the details of treatment and outcome of all children with AML from 1986- 2005 (20 yr.) and ALL from 1989–2003 (15yr.) at King Abdulaziz Medical City, Jeddah, Saudi Arabia. Results: AML 54 patients, 23 boys with median age 5 yr. (range 0.5–14 yr.). Five (9%) had CNS leukemia. Between 1986–1995, 22 pts were treated with BFM based chemotherapy, remaining 32 received UK-AML 10 between 1996–2005. 8/22 (36%) & 5/32 (16%) died of toxicity and 12 (54%) and 8 (25%) died of AML during 1st & 2nd era respectively. With a median follow up of 3 year (.5–10 yr.). The overall survival is 9% in 1st era and 59% in 2nd era. ALL 297 patients were registered. Male 165 pts., median age 5 yr. (range 1–14), WBCs >50,000x109, 55 pts. (19%). T-cell 36 (12%), pre-B 222 (75%) and 29 (10%) unknown. NCI risk classification according to age & WBCs count at presentation as HR 84 (28%), SR 204 (69%). Causes of death; 50/297 (17%) disease recurrence which failed 2nd line chemotherapy, 12/297 (4%) induction death and 11/297 (4%) died of toxicity. Survival by different regimens of chemotherapy were showing UKALL-X 1989–1993, 67 pts.as 55%; UKALL-XI/BFM (1994–1998) 98 pts. As 72%; MRC-97/CCG1991 (1999–2003) 132 pts.87% as overall 5 yr survival. Conclusions: This single center study confirmed that the outcome of children with AML/ALL has improved over last decade. Increasing local experience, advances in supportive care and chemotherapy have contributed to this improvement. No significant financial relationships to disclose.
Contemporary patients with hemophagocytic lymphohistiocytosis: An institutional experience
Authors: Niece J. A. , Ahmad N. , Rogers Z. R. 
Published: March 2020

20022 Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and complex disease whose treatment has improved in the last decade. We report a single institutional experience with HLH to investigate current survival and prognostic significance of common clinical markers at presentation. Methods: Institutional hematology/oncology and pathology databases were searched to identify patients newly diagnosed with HLH, malignant histocytosis or hemophagocytic syndrome from 1995–2006. Patients meeting HLH 2004 diagnostic criteria: fever, cytopenias of >2 cell lines, hypofibrinogenemia, splenomegaly, elevated ferritin, triglycerides, abnormal natural killer cell function and/or soluble interleukin (IL) 2 receptor were included. Labs, age, ethnicity, treatment and outcome were recorded. Univariate analyses were performed. Results: Nine patients (6 female, 3 male) met inclusion criteria. The median age at diagnosis was 3 yrs (range 9 mo-17 yrs). Five patients (56%) were of Hispanic ethnicity. Acute EBV infection was identified in 7 pts (78%) and CMV in 1 (11%). Diagnostic labs revealed median platelet count of 22,000/mm3, hyperbilirubinemia in 7 pts median 7.0 mg/dl, and ALT/AST elevation with median 241/180 U/L. Ferritin elevation and hypofibrinogenemia were prominent in all patients with a median ferritin of 9,092 ng/ml (range 345–130,334) and fibrinogen of 96 mg/ml. Soluble IL-2 receptor was markedly elevated; median 6,403 U/ml (range 4551–27,469). Pts were treated as per HLH 1994 or 2004, with a combination of steroids, IVIG, cyclosporine and VP16. At median follow-up of 12 mo (range 2–49) 8 pts are alive: 4 CR (1 after BMT), 4 PR clinically well with abnormal labs. Death from invasive Rhizopus infection during immunosuppressive therapy in 1. There were no predictive variables for survival identified. Conclusion: The 88% survival of these patients treated with modern HLH therapy significantly exceeds the 55% in prior reports. The large proportion of patients of Hispanic ethnicity distinguishes this from prior series. Whether this ethnic difference accounts for improved survival will need to be studied in larger population. HLH is no longer uniformly fatal, and should be actively sought in critically ill children. No significant financial relationships to disclose.
Optic pathway gliomas in children: A single institution study
Authors: Kebudi R. , Ayrancı O. , Tuncer S. , Ayan I. , Peksayar G. , Gorgun O. , Darendeliler E. 
Published: March 2020

20024 Background: Optic pathway gliomas (OPG) constitute 1–5% of childhood brain tumors, they can occur in patients with NF1. The aim of this study is to evaluate our patients with OPG through a 16 year period. Methods: We reviewed the medical records of 22 patiens treated between Dec. 1990- Dec. 2006. Results: 12 girls and 10 boys (6 mo-19 yrs, median 5yrs) were diagnosed with OPG. 13 patients had NF1.Two had diencephalic syndrome. In 10 the tumor extended to the hypothalamus.Two had leptomeningeal disease, both died despite therapy.Median follow up was 56 months (6–147 mo). 3 patients had stable disease and were followed without treatment, 6 underwent surgery (4 total tumor resection, 2 ventriculoperitoneal shunt; 5 had no additional therapy). 2 patients (14 and 19 years old ) were treated with radiotherapy and 12 (6 mo-9 yrs) received chemotherapy. 3 patients, with stable disease, remained stable. 4 patients, who had total tumor resection, an one with VPS were followed more than 26 months. In two patients , treated with radiotherapy because of progressive disease, clinical response was attained and remained stable. 12 patients recieved chemotherapy, 11 had vincristine 1.5 mg/m2 and carboplatinum 560 mg/m2 in one day every 28 days. Of these 11 patients, 10 patients had clinical response/stable disease after chemotherapy, 1 died of progressive disease. Two patients had hypersensitivity to carboplatinum after 8 courses. There were no other major side effects of treatment. In a patient who had vincristine, CCNU,CTX and PCZ, 7 months after achievement of stable disease with chemotherapy, progressive disease occured, and died. Conclusion: OPG are rare childhood central nervous system tumors. The rarity ot these tumors and their variable course make assesment and standardization of treatment methods difficult. Conservative management can be suggested for asymptomatic or stable cases. Based on the primary location of the tumor and age of the patient; surgery, radiotherapy and chemotherapy can be used as a single treatment modality or in combination. Treatment should be planned on an individual basis. In young children with progressive disease chemotherapy with vincristine, carboplatinum once a month seems to be effective and provides a good quality of life during treatment. No significant financial relationships to disclose.
Three years experience of infantile Wilms tumour at a single institute in a developing country
Authors: Patel A. A. , Patel K. M. , Shah S. A. , Shah P. M. , Shukla S. N. , Parikh B. J. , Anand A. S. , Talati S. S. , Srivastav R. K. , Kattimani K. A. 
Published: March 2020

20028 Background: Wilms tumor (nephroblastoma) is the second most common malignant retroperitoneal tumor. It is the most common primary renal tumour of childhood and is a paradigm for multimodal treatment of a pediatric malignant solid tumor. The median age at diagnosis is 4 years and it is uncommon in infancy. We present a three year retrospective analysis of Wilms tumor in infants treated at out institute. Methods: A total of 16 cases of Wilms tumor were diagnosed in pediatric patients aged one and below between January 2003 to December 2005. Out of these, 11 patients were evaluable. All of them were given treatment as per the National Wilms Tumor Study- 5 protocol. Results: The median age of presentation was 10.8 months, one child was 5 months old rest all were between 10 and 12 months. The male to female ratio was 2.3:1. The most common presenting complaint was mass per abdomen, which was seen in 10 patients, one patient presented with pain in abdomen and hematuria. None of the patients had evidence of any other systemic involvement. 7 patients were in Stage I, 2 each were in stage II and stage III. Triphasic classical type (favorable) was the histopathological subtype in 9 patients and 2 had unfavorable histopathological subtypes. All the 10 cases underwent total Nephrectomy [three at our institute and the rest elsewhere] of the diseased kidney followed by treatment as per the National Wilms Tumor Study- 5 protocol with 50% dose reduction. 7 cases (70%) showed complete remission and presently are under observation. Three cases were lost to follow up after surgery. One patient with stage three disease was given anterior chemotherapy but was lost to follow up after 9 weeks of chemotherapy. Conclusion: Wilms tumor presenting in infancy when treated appropriately has a good outcome although not as good as in older children. No significant financial relationships to disclose.
Phase II trial of bevacizumab and irinotecan in the treatment of malignant gliomas
Authors: Goli K. J. , Desjardins A. , Herndon J. E. , Rich J. N. , Reardon D. A. , Quinn J. A. , Sathornsumetee S. , Bota D. A. , Friedman H. S. , Vredenburgh J. J. 
Published: March 2020

2003 Background: Recurrent malignant gliomas have low response rates to current treatments. Malignant gliomas have high concentrations of VEGF receptors which are poor prognostic indicators. Bevacizumab is a humanized IgG1 monoclonal antibody to VEGF, which is synergistic with chemotherapy for most malignancies. Irinotecan is a topoisomerase 1 inhibitor with modest activity against recurrent malignant gliomas. Methods: We report the mature data for our FDA approved phase II trial of bevacizumab and irinotecan for the treatment of recurrent malignant gliomas. We enrolled 68 patients (35 with grade IV tumors and 33 with grade III tumors.) All patients had progressive disease and received prior radiation therapy and temozolomide. The first 32 patients were treated every other week with bevacizumab 10 mg/kg and irinotecan 125 mg/m2 (non EIAED) or 340 mg/m2 (EIAED). The last 36 patients were treated with irinotecan 125 mg/m2 (non EIAED) or 350 mg/m2 (EIAED) on days 1, 8, 22, and 29 and bevacizumab 15 mg/kg on days 1 and 22. Results: The regimen was well tolerated. Only 1 CNS hemorrhage occurred after 10 cycles of treatment. Eight patients were taken off study for thrombotic complications (four PE, two DVT, one TTP, one thrombotic stroke) and 2 of these patients died (one with PE and one with thrombotic stroke). Two patients were discontinued secondary to grade 2 proteinuria and 3 were discontinued because they required non-neurosurgical surgery. The response rate was 59% (38 PRs and 2 CRs). In Grade IV, the median PFS was 23 weeks (95% confidence intervals 17–34). The 6 month PFS was 43% (95% confidence intervals 29%-63%), the median overall survival was 40 weeks (95% confidence intervals 34–50). In grade III patients the median PFS was 42 weeks, the 6 month PFS was 61% (95% confidence intervals 46%-80%), the medial overall survival was 60 weeks (95% confidence intervals 37%-73%). The follow-up for the second cohort is short with similar efficacy and more toxicity. Conclusion: The combination of bevacizumab and irinotecan is safe and demonstrates superior activity against malignant gliomas. [Table: see text]
M1 medulloblastoma should be considered high risk at any age
Authors: Sanders R. P. , Onar A. , Boyett J. M. , Broniscer A. , Fouladi M. , Boop F. A. , Sanford R. A. , Kun L. E. , Merchant T. M. , Gajjar A. 
Published: March 2020

2016 Background: Metastatic (M) stage is an important prognostic marker in medulloblastoma. With current therapy including higher-dose craniospinal irradiation and dose intensive chemotherapy, older children with metastatic medulloblastoma have had improved survival. Some investigators have suggested that older children with M1 medulloblastoma be treated as average-risk patients. Additionally, the prognostic value of M1 disease in very young children has not been documented. Methods: We retrospectively reviewed the records of all newly diagnosed medulloblastoma patients treated at St. Jude Children’s Research Hospital from 1984 to 2006. Treatment generally included resection and chemotherapy. Older children received post-operative craniospinal and tumor bed irradiation; radiotherapy for younger children depended on treatment era and physician/family preference. We compared event-free and overall survival for patients with M1 disease to that of patients with M0 and M2/M3 disease for both age groups using the Kaplan-Meier method. Results: 286 patients were included. 56 were <3 years old at diagnosis and 230 were =3 years old. Event-free (EFS) and overall survival (OS) by age and M-stage are reported below. Within the younger group, a significant difference in 5-year EFS was detected among M-stage groups (p<0.002 by Mantel-Haenszel test); 5-year EFS for M0 (n=33), M1 (n=5), and M2/M3 (n=18) patients was 67%, 20%, and 22%, respectively. The difference in 5-year EFS by M-stage was also significant for older patients (p<0.0001); 5-year EFS for 154 M0, 13 M1, and 63 M2/M3 patients was 82%, 59%, and 42%, respectively. Results were similar for OS; differences in OS were significant for older (p<0.0001), but not younger (p=0.21) children. Conclusions: Children <3 years old with M1 medulloblastoma fared poorly in our small series. Survival for older children with M1 disease treated with higher-dose CSI was better than that of M2/M3 patients, but still less than optimal; our findings do not support reduction in therapy for either cohort. [Table: see text] No significant financial relationships to disclose.
A phase IIb actively controlled study with the TGF-beta-2 inhibitor AP 12009 for recurrent or refractory anaplastic astrocytoma
Authors: Bogdahn U. , Mahapatra A. , Olyushin V. E. , Mouli C. , Parfenov V. E. , Stockhammer G. , Ludwig S. , Wuerth G. , Heinrichs H. , Schlingensiepen K. 
Published: March 2020

2025 Background: The TGF-β2 antisense phosphorothioate oligonucleotide inhibitor AP 12009 is a targeted anti-tumor therapy for TGF-β2 overexpressing tumors. In three Phase I/II dose escalation studies complete and long-lasting responses were observed in patients with recurrent or refractory anaplastic astrocytoma. Methods: The Phase IIb actively controlled dose finding study G004 is an open-label, randomized trial in adult patients with recurrent or refractory high-grade glioma (HGG) confirmed by central histopathology. 145 patients were randomized into three groups: Low dose AP 12009 (10 μM), high dose AP 12009 (80 μM), or standard chemotherapy, i.e. TMZ (or PCV if TMZ had already failed). Study objective was to compare the efficacy and safety of the three treatment groups. AP 12009 was applied locoregionally by convection- enhanced delivery (CED) with up to 11 treatment cycles (7-day-on, 7-day-off / per cycle). Results: Here we report on patients with recurrent anaplastic astrocytoma (AA, Grade III; GBM patients see separate abstract). 39 AA patients were treated, 12 pts received AP 12009 10 μM (AP-10), 15 pts 80 μM (AP-80), and 12 pts standard chemotherapy (10 pts TMZ, 2 pts PCV). Preliminary safety data reveal no SAEs related to the study drug in the AP-10 and AP-80 groups vs. one in the control group. Survival rates were higher in both AP 12009 groups compared to the chemotherapy group (see table ). In both AP 12009 groups mOS has not yet been reached. Overall survival at present is 28.6 months for the AP-10 group, 24.2 months for the AP-80 group, and 20.2 months for the control group. Dose finding was achieved, as efficacy and safety results for the AP-10 group were superior to those of the AP-80 group (see table ). Conclusion: AP 12009 revealed a positive benefit-risk profile and demonstrated excellent potential as monotherapy for the treatment of recurrent or refractory AA patients, especially for the AP 12009 10 μM group. [Table: see text] [Table: see text]
A pilot study of bevacizumab and stereotactic intensity modulated re-irradiation for recurrent high grade gliomas
Authors: Mohile N. A. , Abrey L. E. , Lymberis S. C. , Karimi S. , Hou B. L. , Gutin P. H. 
Published: March 2020

2028 Background: Bevacizumab is a humanized monoclonal antibody directed at vascular endothelial growth factor A (VEGF-A). Preclinical studies suggest that inhibition of VEGF-A improves glioma response to radiotherapy. The concurrent use of bevacizumab and cranial radiotherapy has not been investigated. The objective of this study is to determine the safety of this combination. Methods: Patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytomas (AA) less than 3.5 cm received bevacizumab (10 mg/kg IV) every 2 weeks. MRI after cycle 1 (28 days) was done to reassess response and for RT planning. Patients then received stereotactic intensity modulated radiation therapy (IMRT): 30Gy in 5 fractions over 15 days. Bevacizumab treatment, given every 2 weeks, was administered during radiotherapy and continued until tumor progression. Brain MRI to assess response was performed after odd cycles. MR T1 and T2* perfusion were performed at baseline and after cycle 1. Results: 12 patients (10 GBM, 2 AA) with median age 53 (range, 30–61) and median KPS 90 (range, 80–100) received a median of 5.5 cycles of bevacizumab. In 1 patient, stereotactic IMRT could not be delivered safely to tumor. Grade III events occurred in 10 patients including hypertension, headache, seizures, neutropenia, hyponatremia and hypophosphatemia. There were no grade IV or V events, no dose limiting toxicities and no intracranial hemorrhage. 7/12 patients had objective responses (3 CR and 4 PR). In 5, SD was the best reported response. At last follow up, ten patients remain on study; 2 have come off for PD. Estimated 6 month PFS is 76%. MR perfusion imaging demonstrated a decrease in mean perfusion values after 1 cycle of bevacizumab. Conclusions: Bevacizumab in combination with RT is safe and well tolerated. Imaging responses and duration of disease control suggest that this regimen is active in this subset of recurrent glioma patients. Further investigations to determine efficacy and possible synergy of bevacizumab with radiotherapy are warranted. [Table: see text]
Potentiation of proteasome inhibitor-induced apoptosis in glioma cells by histone deacetylase inhibitors
Authors: Friday B. , Yu C. , Yang L. , Wigle D. , Sarkaria J. 
Published: March 2020

2038 The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Co-exposure of LBH589 (LBH) and botezomib (btzmb) results in a striking induction of apoptosis, at minimally toxic doses of either drug alone, in established U251, U87, and D37 GBM cell lines, as well as in GBM8 (G-8), GBM10 (G-10), GBM12 (G-12), GBM14 (G-14), and GBM56 (G-56) cells, which have been developed from the Mayo xenograft GBM panel and maintained in short-term cultures. Synergism of apoptosis induction was also observed in U251 cells when co-exposing other HDAC inhibitors, including LAQ824 (LAQ) and trichostatin A (TSA), with another proteasome inhibitor MG132, demonstarting a class effect. In U251 cells, btzmb alone or in combination with LBH decreased Raf-1 levels and inactivated Akt and Erk. Either LBH589 or bortezomib alone increased expression of the cell cycle regulators p21 and p27. Additionally, the combination, but not the individual agents, markedly increased JNK activation. In addition, cell death after exposure to LBH589 and bortezomib is associated with cytochrome c release, Bax translocation, as well as caspase and PARP cleavage. Bax translocation may contribute to the synergistic cytotoxicity of the combination of LBH and btzmb in glioma cells since Bax translocation to mitochondria is known to precede cytochrome c release and apoptosis, but other pathways are likely to be involved. This combination regimen warrants further preclinical and possible clinical study for glioma patients. No significant financial relationships to disclose.