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  • 1
    Language: English
    In: The lancet oncology, 2013, Vol.14 (10), p.999-1008
    Description: Summary Background Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma. Currently, peripheral blood stem cells (PBSC) are infused after myeloablative therapy, but the effect of purging is unknown. We did a randomised study of tumour-selective PBSC purging in stem-cell transplantation for patients with high-risk neuroblastoma. Methods Between March 16, 2001, and Feb 24, 2006, children and young adults (〈30 years) with high-risk neuroblastoma were randomly assigned at diagnosis by a web-based system (in a 1:1 ratio) to receive either non-purged or immunomagnetically purged PBSC. Randomisation was done in blocks stratified by International Neuroblastoma Staging System stage, age, MYCN status, and International Neuroblastoma Pathology classification. Patients and treating physicians were not masked to treatment assignment. All patients were treated with six cycles of induction chemotherapy, myeloablative consolidation, and radiation therapy to the primary tumour site plus meta-iodobenzylguanidine avid metastases present before myeloablative therapy, followed by oral isotretinoin. PBSC collection was done after two induction cycles. For purging, PBSC were mixed with carbonyl iron and phagocytic cells removed with samarium cobalt magnets. Remaining cells were mixed with immunomagnetic beads prepared with five monoclonal antibodies targeting neuroblastoma cell surface antigens and attached cells were removed using samarium cobalt magnets. Patients underwent autologous stem-cell transplantation with PBSC as randomly assigned after six cycles of induction therapy. The primary endpoint was event-free survival and was analysed by intention-to-treat. The trial is registered with ClinicalTrials.gov , number NCT00004188. Findings 495 patients were enrolled, of whom 486 were randomly assigned to treatment: 243 patients to receive non-purged PBSC and 243 to received purged PBSC. PBSC were collected from 229 patients from the purged group and 236 patients from the non-purged group, and 180 patients from the purged group and 192 from the non-purged group received transplant. 5-year event-free survival was 40% (95% CI 33–46) in the purged group versus 36% (30–42) in the non-purged group (p=0·77); 5-year overall survival was 50% (95% CI 43–56) in the purged group compared with 51% (44–57) in the non-purged group (p=0·81). Toxic deaths occurred in 15 patients during induction (eight in the purged group and seven in the non-purged group) and 12 during consolidation (eight in the purged group and four in the non-purged group). The most common adverse event reported was grade 3 or worse stomatitis during both induction (87 of 242 patients in the purged group and 93 of 243 patients in the non-purged group) and consolidation (131 of 177 in the purged group vs 145 of 191 in the non-purged group). Serious adverse events during induction were grade 3 or higher decreased cardiac function (four of 242 in the purged group and five of 243 in the non-purged group) and elevated creatinine (five of 242 in the purged group and six of 243 non-purged group) and during consolidation were sinusoidal obstructive syndrome (12 of 177 in the purged group and 17 of 191 in the non-purged group), acute vascular leak (11 of 177 in the purged group and nine of 191 in the non-purged group), and decreased cardiac function (one of 177 in the purged group and four of 191 in the non-purged group). Interpretation Immunomagnetic purging of PBSC for autologous stem-cell transplantation did not improve outcome, perhaps because of incomplete purging or residual tumour in patients. Non-purged PBSC are acceptable for support of myeloablative therapy of high-risk neuroblastoma. Funding National Cancer Institute and Alex's Lemonade Stand Foundation.
    Subject(s): Hematology, Oncology and Palliative Medicine ; Peripheral Blood Stem Cell Transplantation - adverse effects ; Peripheral Blood Stem Cell Transplantation - methods ; Humans ; Child, Preschool ; Infant ; Risk ; Neuroblastoma - mortality ; Neuroblastoma - therapy ; Disease-Free Survival ; Immunomagnetic Separation ; Adolescent ; Adult ; Child ; Transplantation ; Stem cells ; Neuroblastoma ; Index Medicus
    ISSN: 1470-2045
    E-ISSN: 1474-5488
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Leukemia, 2018-07, Vol.32 (7), p.1515-1528
    Description: The rarity of mixed-phenotype acute leukemia (MPAL) has resulted in diffuse literature consisting of small case series, thus precluding a consensus treatment approach. We conducted a meta-analysis and systematic review to investigate the association of treatment type (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], or "hybrid" regimens), disease response, and survival. We searched seven databases from inception through June 2017 without age or language restriction. Included studies reported sufficient treatment detail for de novo MPAL classified according to the well-established European Group for Immunological Characterization of Acute Leukemias (EGIL) or World Health Organization (WHO2008) criteria. Meta-analyses and multivariable analyses of a patient-level compiled case series were performed for the endpoints of complete remission (CR) and overall survival (OS). We identified 97 reports from 33 countries meeting criteria, resulting in 1,499 unique patients with data, of whom 1,351 had sufficient detail for quantitative analysis of the study endpoints. Using either definition of MPAL, meta-analyses revealed that AML induction was less likely to achieve a CR as compared to ALL regimens, (WHO2008 odds ratio [OR] = 0.33, 95% confidence interval [95% CI] 0.18-0.58; EGIL, OR = 0.18, 95% CI 0.08-0.40). Multivariable analysis of the patient-level data supported poorer efficacy for AML induction (versus ALL: OR = 0.45 95% CI 0.27-0.77). Meta-analyses similarly found better OS for those beginning with ALL versus AML therapy (WHO2008 OR = 0.45, 95% CI 0.26-0.77; EGIL, OR = 0.43, 95% CI 0.24-0.78), but multivariable analysis of patient-level data showed only those starting with hybrid therapy fared worse (hazard ratio [HR] = 2.11, 95% CI 1.30-3.43). MPAL definition did not impact trends within each endpoint and were similarly predictive of outcome. Using either definition of MPAL, ALL-therapy is associated with higher initial remission rates for MPAL and is at least equivalent to more intensive AML therapy for long-term survival. Prospective trials are needed to establish a uniform approach to this heterogeneous disease.
    Subject(s): Animals ; Leukemia, Biphenotypic, Acute - therapy ; Prognosis ; Humans ; Adult ; Treatment Outcome ; Combined Modality Therapy ; Disease Management ; Leukemia, Biphenotypic, Acute - diagnosis ; Child ; Leukemia, Biphenotypic, Acute - mortality ; Remission Induction ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Journal of clinical oncology, 2012-07-20, Vol.30 (21), p.2641-2647
    Description: PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. PATIENTS AND METHODS Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus was also associated with poor OS. CONCLUSION The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.
    Subject(s): Neurology ; Biological and medical sciences ; Medical sciences ; Tumors of the nervous system. Phacomatoses ; Tumors ; Procarbazine - administration & dosage ; Multivariate Analysis ; Prognosis ; Drug Administration Schedule ; Humans ; Risk Factors ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Carboplatin - administration & dosage ; Child, Preschool ; Infant ; Male ; Treatment Outcome ; Brain Neoplasms - drug therapy ; Spinal Cord Neoplasms - drug therapy ; Central Nervous System Neoplasms - pathology ; Thioguanine - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Glioma - pathology ; Vincristine - administration & dosage ; Female ; Central Nervous System Neoplasms - drug therapy ; Child ; Lomustine - administration & dosage ; Glioma - drug therapy ; Original Reports ; Pedi4
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 4
    Language: English
    In: Cancer research (Chicago, Ill.), 2017-09-15, Vol.77 (18), p.5142-5157
    Description: Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship with MSCs is not clear. Here, we have isolated from primary human neuroblastoma tumors a population of αFAP- and FSP-1-expressing CAFs that share phenotypic and functional characteristics with bone marrow-derived MSCs (BM-MSC). Analysis of human neuroblastoma tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages. These cells (designated CAF-MSCs) enhanced neuroblastoma cell proliferation, survival, and resistance to chemotherapy and stimulated neuroblastoma tumor engraftment and growth in immunodeficient mice, indicating an effect independent of the immune system. The protumorigenic activity of MSCs and in xenografted mice was dependent on the coactivation of JAK2/STAT3 and MEK/ERK1/2 in neuroblastoma cells. In a mouse model of orthotopically implanted neuroblastoma cells, inhibition of JAK2/STAT3 and MEK/ERK/1/2 by ruxolitinib and trametinib potentiated tumor response to etoposide and increased overall survival. These data point to a new type of protumorigenic CAF in the tumor microenvironment of neuroblastoma and to STAT3 and ERK1/2 as mediators of their activity. .
    Subject(s): Apoptosis - drug effects ; Cancer-Associated Fibroblasts - metabolism ; Humans ; Cancer-Associated Fibroblasts - drug effects ; Culture Media, Conditioned - pharmacology ; Male ; Janus Kinase 2 - metabolism ; Biomarkers, Tumor - metabolism ; Bone Marrow Cells - drug effects ; Female ; Pyrimidinones - pharmacology ; Antineoplastic Agents - pharmacology ; Gene Expression Regulation, Neoplastic - drug effects ; Tumor Cells, Cultured ; Neuroblastoma - pathology ; STAT3 Transcription Factor - metabolism ; Pyrazoles - pharmacology ; Tumor Microenvironment - drug effects ; Mesenchymal Stromal Cells - drug effects ; Bone Marrow Cells - pathology ; Mesenchymal Stromal Cells - metabolism ; MAP Kinase Kinase 1 - metabolism ; Mice, SCID ; Xenograft Model Antitumor Assays ; Cancer-Associated Fibroblasts - pathology ; Animals ; Mitogen-Activated Protein Kinase 3 - metabolism ; Cell Differentiation - drug effects ; Neuroblastoma - drug therapy ; Mice, Inbred NOD ; Cell Proliferation - drug effects ; Mice ; Neuroblastoma - metabolism ; Mesenchymal Stromal Cells - pathology ; Bone Marrow Cells - metabolism ; Pyridones - pharmacology ; Mitogen-Activated Protein Kinase 1 - metabolism ; Index Medicus
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: HighWire Press (Free Journals)
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Clinical cancer research, 2017-02-01, Vol.23 (3), p.804-813
    Description: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis. The ability of galunisertib to inhibit SMAD activity induced by neuroblastoma patient blood and bone marrow plasmas in neuroblastoma cells was tested. The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined. Neuroblastomas express TGFB1 and TGFBR1 mRNA. Galunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice. In NK cells treated in vitro with exogenous TGFβ1, galunisertib suppressed SMAD2 phosphorylation and restored the expression of DNAM-1, NKp30, and NKG2D cytotoxicity receptors and the TRAIL death ligand, the release of perforin and granzyme A, and the direct cytotoxicity and ADCC of aNK cells against neuroblastoma cells. Addition of galunisertib to adoptive cell therapy with aNK cells plus dinutuximab reduced tumor growth and increased survival of mice injected with two neuroblastoma cell lines or a patient-derived xenograft. Galunisertib suppresses activation of SMAD2 in neuroblastomas and aNK cells, restores NK cytotoxic mechanisms, and increases the efficacy of dinutuximab with aNK cells against neuroblastoma tumors. Clin Cancer Res; 23(3); 804-13. ©2016 AACRSee related commentary by Zenarruzabeitia et al., p. 615.
    Subject(s): Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta - genetics ; Humans ; Neoplasm Proteins - physiology ; Male ; Neoplasm Proteins - antagonists & inhibitors ; Gene Expression Profiling ; Receptors, Transforming Growth Factor beta - physiology ; Smad2 Protein - antagonists & inhibitors ; Quinolines - pharmacology ; RNA, Messenger - biosynthesis ; Protein Processing, Post-Translational - drug effects ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Female ; Phosphorylation - drug effects ; Neuroblastoma - pathology ; Transforming Growth Factor beta1 - biosynthesis ; Pyrazoles - pharmacology ; Killer Cells, Natural - transplantation ; Specific Pathogen-Free Organisms ; Immunotherapy, Adoptive ; Protein-Serine-Threonine Kinases - physiology ; Antibodies, Monoclonal - pharmacology ; RNA, Messenger - genetics ; Protein-Serine-Threonine Kinases - genetics ; Smad2 Protein - metabolism ; Transforming Growth Factor beta1 - genetics ; Transforming Growth Factor beta1 - physiology ; Antineoplastic Agents, Immunological - pharmacology ; Drug Synergism ; Protein-Serine-Threonine Kinases - biosynthesis ; Xenograft Model Antitumor Assays ; Receptors, Transforming Growth Factor beta - biosynthesis ; Animals ; RNA, Neoplasm - biosynthesis ; Receptors, Transforming Growth Factor beta - antagonists & inhibitors ; Cell Line, Tumor ; RNA, Neoplasm - genetics ; Mice, Inbred NOD ; Mice ; Neuroblastoma - metabolism ; Cytotoxicity, Immunologic ; Index Medicus ; TGFβR1 inhibitor ; dinutuximab ; adoptive cell therapy ; galunisertib ; immunotherapy
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Leukemia, 2018-12-28, Vol.33 (4), p.884-892
    Description: Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/ refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was welltolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.
    Subject(s): Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Antibodies, Monoclonal, Humanized - therapeutic use ; Prognosis ; Humans ; Salvage Therapy ; Child, Preschool ; Neoplasm Recurrence, Local - drug therapy ; Male ; Survival Rate ; Antineoplastic Agents - therapeutic use ; Remission Induction ; Neoplasm Recurrence, Local - pathology ; Young Adult ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Adolescent ; Adult ; Female ; Inotuzumab Ozogamicin ; Retrospective Studies ; Child ; Drug Resistance, Neoplasm - drug effects ; Cancer immunotherapy ; Acute lymphocytic leukaemia
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Journal of clinical oncology, 2010-02-01, Vol.28 (4), p.648-654
    Description: Despite improvements in treatment, approximately 20% of patients with acute lymphoblastic leukemia (ALL) experience relapse and do poorly. The Therapeutic Advances in Childhood Leukemia (TACL) Consortium was assembled to assess novel drugs for children with resistant leukemia. We hypothesize that novel agents and combinations that fail to improve baseline complete remission rates in comparable populations are unlikely to contribute to better outcomes and should be abandoned. We sought to define response rates and disease-free survival (DFS) rates in patients treated at TACL institutions, which could serve as a comparator for future studies. We performed a retrospective cohort review of patients with relapsed and refractory ALL previously treated at TACL institutions between the years of 1995 and 2004. Data regarding initial and relapsed disease characteristics, disease response, and survival were collected and compared with those of published reports. Complete remission (CR) rates (mean +/- SE) were 83% +/- 4% for early first marrow relapse, 93% +/- 3% for late first marrow relapse, 44% +/- 5% for second marrow relapse, and 27% +/- 6% for third marrow relapse. Five-year DFS rates in CR2 and CR3 were 27% +/- 4% and 15% +/- 7% respectively. We generally confirm a 40% CR rate for second and subsequent relapse, but our remission rate for early first relapse seems better than that reported in the literature (83% v approximately 70%). Our data may allow useful modeling of an expected remission rate for any population of patients who experience relapse.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Tumors ; Prognosis ; Follow-Up Studies ; Humans ; Salvage Therapy ; Child, Preschool ; Drug Resistance, Neoplasm ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - pathology ; Young Adult ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy ; Adult ; Female ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Child ; Infant, Newborn ; Neoplasm Recurrence, Local - therapy ; Hematopoietic Stem Cell Transplantation ; Survival Rate ; Treatment Outcome ; Combined Modality Therapy ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Cohort Studies ; Index Medicus ; Original Reports ; Pedi2
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Journal of clinical oncology, 2012-09-10, Vol.30 (26), p.3174-3180
    Description: In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, "B" symptoms, and nodular sclerosis histology were risk factors for inferior EFS. With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Tumors ; Humans ; Child, Preschool ; Male ; Treatment Outcome ; Combined Modality Therapy ; Disease-Free Survival ; Hodgkin Disease - radiotherapy ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Survival Analysis ; Hodgkin Disease - drug therapy ; Hodgkin Disease - mortality ; Female ; Child ; Index Medicus ; Original Reports ; Pedi9
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Journal of clinical oncology, 2006-09-01, Vol.24 (25), p.4202-4208
    Description: To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies. Four hundred twenty-one patients between 3 years and 21 years of age with nondisseminated medulloblastoma (MB) were prospectively randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of posterior fossa RT, plus one of two adjuvant chemotherapy regimens: lomustine (CCNU), cisplatin, and vincristine; or cyclophosphamide, cisplatin, and vincristine. Results Forty-two of 421 patients enrolled were excluded from analysis. Sixty-six of the remaining 379 patients had incompletely assessable postoperative studies. Five-year EFS and survival for the cohort of 379 patients was 81% +/- 2.1% and 86% +/- 9%, respectively (median follow-up over 5 years). EFS was unaffected by sex, race, age, treatment regimen, brainstem involvement, or excessive anaplasia. EFS was detrimentally affected by neuroradiographic unassessability. Patients with areas of frank dissemination had a 5-year EFS of 36% +/- 15%. Sixty-seven percent of progressions had some component of dissemination. There were seven second malignancies. Infections occurred more frequently on the cyclophosphamide arm and electrolyte abnormalities were more common on the CCNU regimen. This study discloses an encouraging EFS rate for children with nondisseminated MB treated with reduced-dose craniospinal radiation and chemotherapy. Additional, careful, step-wise reductions in CSRT in adequately staged patients may be possible.
    Subject(s): Neurology ; Biological and medical sciences ; Medical sciences ; Tumors of the nervous system. Phacomatoses ; Tumors ; Cyclophosphamide - administration & dosage ; Prognosis ; Humans ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Child, Preschool ; Male ; Cisplatin - administration & dosage ; Medulloblastoma - radiotherapy ; Chemotherapy, Adjuvant - adverse effects ; Radiotherapy, Adjuvant - adverse effects ; Medulloblastoma - pathology ; Vincristine - administration & dosage ; Adult ; Female ; Cerebellar Neoplasms - pathology ; Child ; Radiotherapy Dosage ; Cerebellar Neoplasms - drug therapy ; Risk Factors ; Neoplasms, Second Primary - diagnosis ; Disease-Free Survival ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Survival Analysis ; Medulloblastoma - drug therapy ; Neoplasm Staging ; Cerebellar Neoplasms - radiotherapy ; Lomustine - administration & dosage
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 10
    Language: English
    In: Archives of pathology & laboratory medicine (1976), 2016-03, Vol.140 (3), p.267-275
    Description: Molecular diagnostics allow for rapid identification and detection of resistance markers of bloodstream infection, with a potential for accelerated antimicrobial optimization and improved patient outcomes. Although the impact of rapid diagnosis has been reported, studies in pediatric patients are scarce. To determine the impact of a molecular blood-culture assay that identifies a broad-spectrum of pathogens and resistance markers in pediatric patients with gram-positive bloodstream infections. Data on the time to antimicrobial optimization, the length of hospitalization, and the hospital cost following implementation of a rapid assay were prospectively collected and compared with corresponding preimplementation data. There were 440 episodes from 383 patients included, 221 preimplementation episodes and 219 postimplementation episodes. Overall time to antimicrobial optimization was shortened by 12.5 hours (P = .006), 11.9 hours (P = .005) for bloodstream infections of Staphylococcus aureus specifically. Duration of antibiotics for those with probable blood-culture contamination with coagulase-negative staphylococci was reduced by 36.9 hours (P 〈 .001). Median length of stay for patients admitted to general pediatric units was 1.5 days shorter (P = .04), and median hospital cost was $3757 (P = .03) less after implementation. For S aureus bloodstream infections, median length of stay and hospital cost were decreased by 5.6 days (P = .01) and $13,341 (P = .03), respectively. Implementation of molecular assay for the detection of gram-positive pathogens and resistance markers significantly reduced time to identification and resistance detection, resulting in accelerated optimization of therapy, shorter length of stay, and decreased health care cost.
    Subject(s): Gram-Positive Bacterial Infections - economics ; Hospital Costs ; Prospective Studies ; Gram-Positive Bacteria - drug effects ; Humans ; Drug Resistance, Bacterial ; Hospitals, Pediatric ; Infant ; Blood - microbiology ; Bacteremia - economics ; Bacterial Proteins - analysis ; Cost Savings ; Bacteremia - microbiology ; Anti-Bacterial Agents - therapeutic use ; Gram-Positive Bacterial Infections - microbiology ; DNA, Bacterial - analysis ; Gram-Positive Bacteria - growth & development ; Child ; Anti-Bacterial Agents - economics ; Biomarkers - metabolism ; Length of Stay ; Costs and Cost Analysis ; Time-to-Treatment ; Bacteremia - drug therapy ; Bacterial Proteins - genetics ; Bacteremia - diagnosis ; Gram-Positive Bacterial Infections - diagnosis ; Gram-Positive Bacteria - classification ; Molecular Typing - economics ; Gram-Positive Bacteria - isolation & purification ; Los Angeles ; Gram-Positive Bacterial Infections - drug therapy ; Cohort Studies ; Pediatrics ; Medical research ; Drug resistance in microorganisms ; Medical examination ; Children's hospitals ; Staphylococcus aureus infections ; Blood ; Infection ; Medicine, Experimental ; Children ; Comparative analysis ; Health aspects ; Medical care, Cost of ; Index Medicus ; Abridged Index Medicus
    ISSN: 0003-9985
    ISSN: 1543-2165
    E-ISSN: 1543-2165
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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