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  • 1
    Article
    Article
    2015
    ISSN: 1470-2045 
    Language: English
    In: The lancet oncology, 2015, Vol.16 (16), p.1580-1581
    Subject(s): Hematology, Oncology and Palliative Medicine ; Asparaginase - administration & dosage ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Escherichia coli - enzymology ; Escherichia coli Proteins - administration & dosage ; Humans ; Female ; Male ; Antineoplastic Agents - administration & dosage ; Polyethylene Glycols - administration & dosage ; 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: Bone marrow transplantation (Basingstoke), 2020-10, Vol.55 (10), p.1900-1905
    Description: Italy is the second exposed country worldwide, after China, and Lombardia is the most affected region in Italy, with more than half of the national cases, with 13% of whom being healthcare professionals. The Clinica Pediatrica Università degli Studi di Milano Bicocca is a general pediatric and hematology oncology and transplant center embedded within the designated COVID-19 general Hospital San Gerardo in Monza, located in Lombardia, Italy. Preventive and control measures specifically undertaken to cope with the emergency within hemato-oncology, transplant, and outpatient unit in the pediatric department have been described. Preliminary COVID-19 experiences with the first Italian pediatric hemato-oncology patients are reported. The few available data regarding pediatrics and specifically hemato-oncological patients are discussed. The purpose of this report is to share pediatric hemato-oncology issues encountered in the first few weeks of the COVID-19 outbreak in Italy and to alert healthcare professionals worldwide to be prepared accordingly.
    Subject(s): Coronavirus Infections - prevention & control ; Hematology - organization & administration ; Humans ; Middle Aged ; Pandemics - prevention & control ; Child, Preschool ; Infant ; Male ; Transplantation ; Infection Control - methods ; Medical Oncology - organization & administration ; COVID-19 ; Pediatrics - organization & administration ; Stem Cell Transplantation ; Young Adult ; Neoplasms - complications ; SARS-CoV-2 ; Coronavirus Infections - epidemiology ; Pneumonia, Viral - epidemiology ; Aged, 80 and over ; Betacoronavirus ; Adult ; Female ; Child ; Infant, Newborn ; Hospitals ; Outpatients ; Pneumonia, Viral - prevention & control ; Adolescent ; Italy - epidemiology ; Aged ; Pediatrics ; Clinics ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    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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  • 3
    Language: English
    In: The New England journal of medicine, 2020-05-07, Vol.382 (19), p.1811-1822
    Description: Primary hemophagocytic lymphohistiocytosis, a rare genetic immune disorder characterized by hyperinflammation, manifests in infancy and is associated with high mortality. In a study involving 34 children, an antibody to interferon-γ (emapalumab) produced responses in 65%; it served as a bridge to marrow transplantation in 70% of those who had received previous treatment.
    Subject(s): Antibodies, Neutralizing - administration & dosage ; Infections - etiology ; Humans ; Antibodies, Monoclonal - adverse effects ; Chemokine CXCL9 - blood ; Child, Preschool ; Infant ; Male ; Lymphohistiocytosis, Hemophagocytic - mortality ; Interferon-gamma - antagonists & inhibitors ; Anti-Inflammatory Agents - administration & dosage ; Antibodies, Neutralizing - adverse effects ; Female ; Drug Therapy, Combination ; Child ; Dexamethasone - administration & dosage ; Lymphohistiocytosis, Hemophagocytic - drug therapy ; Kaplan-Meier Estimate ; Hematopoietic Stem Cell Transplantation ; Treatment Outcome ; Lymphohistiocytosis, Hemophagocytic - therapy ; Lymphohistiocytosis, Hemophagocytic - complications ; Antibodies, Monoclonal - administration & dosage ; Adolescent ; Age of Onset ; Histoplasmosis ; Dexamethasone ; Statistical analysis ; Laboratories ; Toxicity ; Mortality ; Stem cell transplantation ; Histiocytosis ; Patients ; Hemopoiesis ; Confidence intervals ; Hypotheses ; γ-Interferon ; Lymphocytosis ; Chemokines ; Index Medicus ; Abridged Index Medicus
    ISSN: 0028-4793
    E-ISSN: 1533-4406
    Source: Single 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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  • 4
    Language: English
    In: Journal of clinical oncology, 2013-02-10, Vol.31 (5), p.599-607
    Description: Purpose In pediatric relapsed acute myeloid leukemia (AML), optimal reinduction therapy is unknown. Studies suggest that liposomal daunorubicin (DNX; DaunoXome; Galen, Craigavon, United Kingdom) is effective and less cardiotoxic, which is important in this setting. These considerations led to a randomized phase III study by the International Berlin-Frankfurt-Munster Study Group. Patients and Methods Patients with relapsed or primary refractory non-French-American-British type M3 AML who were younger than 21 years of age were eligible. Patients were randomly assigned to fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) or to FLAG plus DNX in the first reinduction course. The primary end point was status of the bone marrow (BM) sampled shortly before the second course of chemotherapy (the day 28 BM). Data are presented according to intention-to-treat for all 394 randomly assigned patients (median follow-up, 4.0 years). Results The complete remission (CR) rate was 64%, and the 4-year probability of survival (pOS) was 38% (SE, 3%). The day 28 BM status (available in 359 patients) was good ( Conclusion DNX added to FLAG improves early treatment response in pediatric relapsed AML. Overall long-term survival was similar, but CBF-AML showed an improved survival with FLAG/DNX. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far. J Clin Oncol 31:599-607. (C) 2013 by American Society of Clinical Oncology
    Subject(s): AML ; SURVIVAL ; ANTHRACYCLINE CARDIOTOXICITY ; THERAPY ; ACUTE MYELOGENOUS LEUKEMIA ; INITIAL TREATMENT ; PHASE-II ; CYTARABINE ; CHILDREN ; LONG ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Humans ; Kaplan-Meier Estimate ; Child, Preschool ; Male ; Treatment Outcome ; International Cooperation ; Vidarabine - analogs & derivatives ; Remission Induction ; Cytarabine - administration & dosage ; Antibiotics, Antineoplastic - administration & dosage ; Leukemia, Myeloid, Acute - mortality ; Confounding Factors (Epidemiology) ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Leukemia, Myeloid, Acute - drug therapy ; Female ; Vidarabine - administration & dosage ; Liposomes ; Odds Ratio ; Child ; Research Design ; Daunorubicin - administration & dosage ; Granulocyte Colony-Stimulating Factor - administration & dosage
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 5
    Language: English
    In: British journal of haematology, 2019-05, Vol.185 (3), p.623-627
    Description: Table SVI. Bioavailability and Safety of Midostaurin Oral Solution and Capsule Formulations in Healthy Volunteers in Study A2108
    Subject(s): relapsed/refractory ; midostaurin ; acute leukaemia ; FLT3 ; paediatric ; Follow-Up Studies ; Humans ; Leukemia, Myeloid, Acute - metabolism ; Staurosporine - adverse effects ; Child, Preschool ; Infant ; Male ; Staurosporine - analogs & derivatives ; Survival Rate ; Disease-Free Survival ; Adolescent ; Leukemia, Myeloid, Acute - drug therapy ; Female ; Child ; Staurosporine - administration & dosage ; Relapse ; Oral medication ; Analysis ; Diseases ; Index Medicus ; Medicin och hälsovetenskap
    ISSN: 0007-1048
    ISSN: 1365-2141
    E-ISSN: 1365-2141
    Source: Alma/SFX Local Collection
    Source: SWEPUB Freely available online
    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: British journal of haematology, 2019-08, Vol.186 (3), p.420-430
    Description: Summary Eradicating the malignant stem cell is the ultimate challenge in the treatment of leukaemia. Leukaemic stem cells (LSC) hijack the normal haemopoietic niche, where they are mainly protected from cytotoxic drugs. The anti‐leukaemic effect of L‐asparaginase (ASNase) has been extensively investigated in acute lymphoblastic leukaemia, but only partially in acute myeloid leukaemia (AML). We explored the susceptibility of AML‐LSC to ASNase as well as the role of the two major cell types that constitute the bone marrow (BM) microenvironment, i.e., mesenchymal stromal cells (MSC) and monocytes/macrophages. Whilst ASNase was effective on both CD34+CD38+ and CD34+CD38− LSC fractions, MSC and monocytes/macrophages partially counteracted the effect of the drug. Indeed, the production of cathepsin B, a lysosomal cysteine protease, by BM monocytic cells and by AML cells classified as French‐American‐British M5 is related to the inactivation of ASNase. Our work demonstrates that, while MSC and monocytes/macrophages may provide a protective niche for AML cells, ASNase has a cytotoxic effect on AML blasts and, importantly, LSC subpopulations. Thus, these features should be considered in the design of future clinical studies aimed at testing ASNase efficacy in AML patients.
    Subject(s): leukaemic stem cells ; acute myeloid leukaemia ; asparaginase ; bone marrow microenvironment ; cathepsin B ; Cathepsins ; Medicine, Experimental ; Medical research ; Cysteine ; Analysis ; Stem cells ; Index Medicus
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    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: Pediatric blood & cancer, 2020-08, Vol.67 (8), p.e28410-n/a
    Subject(s): COVID-19 ; Coronavirus Infections ; Medical Oncology ; SARS-CoV-2 ; Pandemics ; Hematology ; Humans ; Betacoronavirus ; Italy ; Pneumonia, Viral ; Child ; Index Medicus
    ISSN: 1545-5009
    E-ISSN: 1545-5017
    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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  • 8
    Language: English
    In: British journal of haematology, 2017-04, Vol.177 (1), p.116-126
    Description: Summary In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow‐cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica‐AML 2002/01 trial. At the end of the first induction course, MRD was 〈0·1% in 69, 0·1–1% in 16 and 〉1% in 51 patients. The 8‐year disease‐free survival (DFS) of 125 children in morphological complete remission and with MRD 〈0·1%, 0·1–1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P 〈 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD 〈0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow‐cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post‐remission treatment.
    Subject(s): Minimal residual disease ; Acute myeloid leukaemia ; Paediatric; Risk group ; Flow‐cytometry ; Multivariate Analysis ; Prognosis ; Follow-Up Studies ; Humans ; Child, Preschool ; Immunophenotyping ; Infant ; Male ; Treatment Outcome ; Leukemia, Myeloid, Acute - mortality ; Flow Cytometry ; Leukemia, Myeloid, Acute - diagnosis ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Neoplasm, Residual - diagnosis ; Adolescent ; Survival Analysis ; Leukemia, Myeloid, Acute - drug therapy ; Female ; Child ; Infant, Newborn ; Medical research ; Analysis ; Medicine, Experimental ; Transplantation ; Children ; Chromosomes ; Hematopoietic stem cells ; Diseases ; Index Medicus
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    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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  • 9
    Language: English
    In: JAMA : the journal of the American Medical Association, 2021-03-02, Vol.325 (9), p.843-854
    Description: IMPORTANCE: Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). OBJECTIVE: To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. DESIGN, SETTING, AND PARTICIPANTS: In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, 〈5% blasts) or with M2 marrow (blasts ≥5% and 〈25%) at randomization. INTERVENTION: Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 μg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. MAIN OUTCOMES AND MEASURES: The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events. RESULTS: A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P 〈 .001; hazard ratio [HR], 0.33 [95% CI, 0.18-0.61]). Deaths occurred in 8 patients (14.8%) in the blinatumomab group and 16 (29.6%) in the consolidation chemotherapy group. The overall survival HR was 0.43 (95% CI, 0.18-1.01). Minimal residual disease remission was observed in more patients in the blinatumomab vs consolidation chemotherapy group (90% [44/49] vs 54% [26/48]; difference, 35.6% [95% CI, 15.6%-52.5%]). No fatal adverse events were reported. In the blinatumomab vs consolidation chemotherapy group, the incidence of serious adverse events was 24.1% vs 43.1%, respectively, and the incidence of adverse events greater than or equal to grade 3 was 57.4% vs 82.4%. Adverse events leading to treatment discontinuation were reported in 2 patients in the blinatumomab group. CONCLUSIONS AND RELEVANCE: Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02393859
    Subject(s): Recurrence ; Follow-Up Studies ; Humans ; Child, Preschool ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Antineoplastic Agents - therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy ; Antineoplastic Agents - adverse effects ; Immunotherapy ; Female ; Leukemia, B-Cell - drug therapy ; Leukemia, B-Cell - mortality ; Child ; Risk Factors ; Kaplan-Meier Estimate ; Hematopoietic Stem Cell Transplantation ; Survival Rate ; Combined Modality Therapy ; Antibodies, Bispecific - therapeutic use ; Disease-Free Survival ; Antibodies, Bispecific - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Consolidation Chemotherapy - adverse effects ; Index Medicus ; Abridged Index Medicus
    ISSN: 0098-7484
    E-ISSN: 1538-3598
    Source: American Medical Association Journals Backfile (through 1997)
    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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  • 10
    Language: English
    In: Journal of clinical pathology, 2019-08, Vol.72 (8), p.558-561
    Description: Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant genetic disorder characterised by prenatal and postnatal growth and mental retardation, facial dysmorphism and upper limb abnormalities. Germline mutations of cohesin complex genes SMC1A, SMC3, RAD21 or their regulators NIPBL and HDAC8 have been identified in CdLS as well as somatic mutations in myeloid disorders. We describe the first case of a paediatric patient with CdLS with B-cell precursor Acute Lymphoblastic Leukaemia (ALL). The patient did not show any unusual cytogenetic abnormality, and he was enrolled into the high risk arm of AIEOP-BFM ALL2009 protocol because of slow early response, but 3 years after discontinuation, he experienced an ALL relapse. We identified a heterozygous mutation in exon 46 of NIPBL, causing frameshift and a premature stop codon (RNA-Targeted Next generation Sequencing Analysis). The analysis of the family indicated a de novo origin of this previously not reported deleterious variant. As for somatic cohesin mutations in acute myeloid leukaemia, also this ALL case was not affected by aneuploidy, thus suggesting a major impact of the non-canonical role of NIPBL in gene regulation. A potential biological role of NIPBL in leukaemia has still to be dissected.
    Subject(s): Leukemia ; Genes ; Families & family life ; Genetic testing ; Down syndrome ; Mutation ; Bioinformatics ; Deoxyribonucleic acid--DNA ; Cancer ; Tumors
    ISSN: 0021-9746
    E-ISSN: 1472-4146
    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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