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  • American Society of Clinical Oncology (ASCO)  (10)
  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2003
    In:  Journal of Clinical Oncology Vol. 21, No. 7 ( 2003-04-01), p. 1347-1351
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 21, No. 7 ( 2003-04-01), p. 1347-1351
    Abstract: Purpose: To evaluate the pattern of neurological late effects in patients who have received surgery only for a brain tumor in childhood and to identify possible risk factors for neurological sequelae. Patients and Methods: The medical, histologic, and operative records were reviewed for 65 consecutive patients operated for a benign brain tumor from 1970 to 1997, and all patients were re-examined after a median length of follow-up of 10.7 years. Thirty-four patients had posterior fossa tumors, 22 patients had cerebral hemisphere tumors, and nine patients had midline tumors. Results: At the time of follow-up, 20 patients (31%) had no neurological deficits, 22 patients (34%) had minor deficits that did not interfere with their daily life activities, and 23 patients (35%) had moderate or severe deficits such as severe ataxia, spastic paresis, seriously reduced vision, or epilepsy with more than two seizures per year. Fourteen of the 31 patients (45%) registered with ataxia preoperatively had recovered fully. Six of seven patients had persistence of a pre- or postoperatively developed hemiparesis. Thirteen of 23 patients had persistence of cranial nerve deficits that developed second to surgery. Fifty-five percent of the 18 patients with seizures at diagnosis were seizure-free at follow-up. At follow-up both ataxia and hemiparesis were significantly more frequent among females (P = .02 and P = .03, respectively). Conclusion: In patients who received operation as the only treatment for their brain tumor, there was a good chance of total or partial recovery of preoperative and postoperative neurological deficits, although only one third of the patients will have no long-term neurological deficits.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2003
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 13 ( 2005-05-01), p. 3030-3037
    Abstract: Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. Patients and Methods Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H 2 15 O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest–based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 ± 0.5, four grade 3 tumors had a mean index of 2.47 ± 1.07, 10 grade 2 tumors had a mean index of 1.34 ± 0.73, and eight of 12 grade 1 tumors had a mean index of −0.31 ± 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P 〈 .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P 〈 .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P 〈 .01). H 2 15 O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. Conclusion FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2005
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 27 ( 2015-09-20), p. 2938-2948
    Abstract: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 2 ( 2020-01-10), p. 145-154
    Abstract: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. PATIENTS AND METHODS We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. RESULTS Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. CONCLUSION Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 21, No. 7 ( 2003-04-01), p. 1332-1339
    Abstract: Purpose: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). Patients and Methods: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group). Results: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P = .00003), high WBC at diagnosis (P = .03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P = .002), and high average neutrophil counts during maintenance therapy (P = .0009), with a significant interaction between sex and randomization group (P = .0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P = .001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P 〈 .0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P = .03; boys 19.3 v 18.0 U/mL, P = .04). Conclusion: Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2003
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO)
    Abstract: Outcome improvement for T-cell acute lymphoblastic leukemia and Induction failure in a contemporary treatment era.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 12 ( 2013-04-20), p. 1562-1568
    Abstract: To minimize the risk of late effects in pediatric Hodgkin lymphoma (HL) by omitting radiotherapy (RT) in patients in complete remission (CR) after chemotherapy and reducing the standard radiation dose to 20 Gy in patients in incomplete remission. Patients and Methods Between 1995 and 2001, 925 patients with classical HL (cHL) were registered from seven European countries in German Society of Pediatric Oncology and Hematology Hodgkin Lymphoma Trial 95. Patients in treatment group 1 (TG1; early stages) received two cycles of vincristine, prednisone, procarbazine, and doxorubicin or vincristine, prednisone, etoposide, and doxorubicin chemotherapy; additional two or four cycles of cyclophosphamide, vincristine, prednisone, and procarbazine were added in TG2 (intermediate stages) or TG3 (advanced stages), respectively. Patients in CR (assessed by computed tomography or magnetic resonance imaging) did not undergo RT. Those with tumor volume reduction more than 75% received reduced involved-field RT with 20 Gy and an additional 10- or 15-Gy boost only for larger residuals. Results Rates of overall survival, progression-free survival (PFS), and event-free survival at 10 years were (± SE) 96.3% ± 0.6%, 88.2% ± 1.1%, and 85.4% ± 1.3%, respectively. PFS for TG1 patients without or with RT was 97.0% ± 2.1% versus 92.2% ± 1.7% (P = .214) but was unsatisfactory for nonirradiated patients in TG2 (68.5% ± 7.4% v 91.4% ± 1.9%; P 〈 .0001), with similar but not significant results in TG3 (82.6% ± 5.4% v 88.7% ± 2.0%, P = .259). Reduction of the standard radiation dose from 25 to 20 Gy did not increase failure rate. Conclusion RT can be omitted in early stage HL in so defined CR following this chemotherapy. RT with 20(−35) Gy proved to be sufficient in patients with incomplete remission following chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 19 ( 2019-07-01), p. 1638-1646
    Abstract: Asparaginase is an essential drug in childhood acute lymphoblastic leukemia (ALL) therapy and is frequently given for months to obtain continuous asparagine depletion. We randomly assigned patients to continuous versus intermittent pegylated-asparaginase (PEG-asp) treatment, hypothesizing there would be decreased toxicity with unchanged efficacy. METHODS Children (median age, 4.2 years) treated for non–high-risk ALL according to the Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol received five intramuscular PEG-asp injections (1,000 IU/m 2 ) every two weeks and were then randomly assigned to additional three doses (6-week intervals [experimental arm], n = 309) versus 10 doses (2-week intervals [standard arm] , n = 316). The primary end point was noninferior (6% margin) disease-free survival. Toxicity reduction was a secondary end point. Occurrence of asparaginase-associated hypersensitivity, pancreatitis, osteonecrosis, and thromboembolism were prospectively registered. RESULTS After a median follow-up of 4.1 years, the 5-year disease-free survival was 92.2% (95% CI, 88.6 to 95.8) and 90.8% (95% CI, 87.0 to 94.6) in the experimental and standard arms, respectively. The 3-year cumulative incidence of any first asparaginase-associated toxicity (hypersensitivity [n = 13]; osteonecrosis [n = 29] ; pancreatitis [n = 24]; thromboembolism [n = 17] ) was 9.3% in the experimental arm and 18.1% in the standard arm ( P = .001). Asparaginase-associated toxicity reduction was confirmed in sex- and risk-group–adjusted Cox regression analysis stratified by age (≥ 10 and 〈 10 years; hazard ratio, 0.48; P = .001). The experimental arm had the lowest incidences of all four toxicities, reaching significance for pancreatitis (6-month risk, 5.8% v 1.3%; P = .002). CONCLUSION The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 7 ( 2023-03-01), p. 1404-1422
    Abstract: We aimed to study prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/ KMT2A rearrangements treated with chemotherapy regimens between 1995 and 2010. PATIENTS AND METHODS Data were retrospectively retrieved from 629 patients with 11q23/ KMT2A-rearranged ALL from 17 members of the Ponte-di-Legno Childhood ALL Working Group. Clinical and biologic characteristics, early response assessed by minimal residual disease at the end of induction (EOI) therapy, and allo-HSCT were analyzed for their impact on outcomes. RESULTS A specific 11q23/ KMT2A translocation partner gene was identified in 84.3% of patients, with the most frequent translocations being t(4;11)(q21;q23) (n = 273; 51.5%), t(11;19)(q23;p13.3) (n = 106; 20.0%), t(9;11)(p21_22;q23) (n = 76; 14.3%), t(6;11)(q27;q23) (n = 20; 3.8%), and t(10;11)(p12;q23) (n = 14; 2.6%); 41 patients (7.7%) had less frequently identified translocation partner genes. Patient characteristics and early response varied among subgroups, indicating large biologic heterogeneity and diversity in therapy sensitivity among 11q23/ KMT2A-rearranged ALL. The EOI remission rate was 93.2%, and the 5-year event-free survival (EFS) for the entire cohort was 69.1% ± 1.9%, with a range from 41.7% ± 17.3% for patients with t(9;11)-positive T-ALL (n = 9) and 64.8% ± 3.0% for patients with t(4;11)-positive B-ALL (n = 266) to 91.2% ± 4.9% for patients with t(11;19)-positive T-ALL (n = 34). Low EOI minimal residual disease was associated with favorable EFS, and induction failure was particularly predictive of nonresponse to further therapy and relapse and poor EFS. In addition, EFS was not improved by allo-HSCT compared with chemotherapy only in patients with both t(4;11)-positive B-ALL (n = 64 v 51; P = .10) and 11q23/ KMT2A-rearranged T-ALL (n = 16 v 10; P = .69). CONCLUSION Compared with historical data, prognosis of patients with noninfant 11q23/ KMT2A-rearranged ALL has improved, but allo-HSCT failed to affect outcome. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 19 ( 2013-07-01), p. 2469-2476
    Abstract: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P 〈 .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m 2 per week and mercaptopurine of at least 75 mg/m 2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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