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  • 1
    Online Resource
    Online Resource
    Cytoreduction and prognosis in acute lymphoblastic leukemia--the importance of early marrow response: report from the Childrens Cancer Group.
    American Society of Clinical Oncology (ASCO) ; 1996
    In:  Journal of Clinical Oncology Vol. 14, No. 2 ( 1996-02), p. 389-398
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 14, No. 2 ( 1996-02), p. 389-398
    Abstract: To quantify the residual marrow lymphoblast fraction that best defines patients at high risk for relapse, and the optimal time for assessment during remission induction. PATIENTS AND METHODS The residual lymphoblast percentage was evaluated on day 7 (n = 220) and day 14 (n = 205) during a four- or five-drug induction in patients with poor prognostic factors. The rate of cytoreduction was related to event-free survival (EFS) and other factors. RESULTS On the New York (NY) regimen, 68%, 14%, and 18%, and on the Berlin-Frankfurt-Munster (BFM) regimen, 56%, 15%, and 29% of patients had M1 ( 〈 5% blasts), M2 (5-25%), or M3 ( 〉 25%) responses on day 7 (P = .075). On day 14, the corresponding values were 87%, 6%, 7% on NY and 84%, 8%, 8% on BFM. For patients who achieved remission by day 28 and a day-7 marrow rating of M1, M2, or M3, the 6-year EFS rate was 78%, 61%, and 49% (P 〈 .001). The day-14 ratings predicted for a 72%, 32%, or 40% EFS (P 〈 .001). Patients with 5% to 10% blasts day 7 had three times as many events as those with less than 5% and had no better EFS than those with 11% to 25% blasts. Patients with a WBC count more than 200,000/microL at diagnosis and an M1 day 7 marrow had an EFS rate of 69%, while for those with M2 or M3, the EFS rate was 41%. Day-7 marrow had greater prognostic significance than the day-14 evaluation. For slow responders on day 7, the day-14 marrow provided additional information. EFS for patients who achieved M1 by day 14 was 65%. EFS decreased to 20% for those still M2 or M3 on day 14. Day-7 and -14 evaluations had significance for patients of all ages and WBC levels. CONCLUSION Marrow aspiration on day 7 of therapy provided more useful information than that on day 14. However, day-14 marrow provided additional information for patients with a poor day-7 response. The rate of cytoreduction is a powerful, independent prognostic factor that can identify patients with a slow early response who are at risk for a short remission duration.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1996.14.2.389
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1996
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group.
    American Society of Clinical Oncology (ASCO) ; 1998
    In:  Journal of Clinical Oncology Vol. 16, No. 2 ( 1998-02), p. 527-535
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 16, No. 2 ( 1998-02), p. 527-535
    Abstract: The nonrandom translocation t(1;19) has been associated with poor outcome in pediatric B-lineage acute lymphoblastic leukemia (ALL). Because most patients treated by contemporary therapies now achieve improved outcomes, we have reassessed the prognostic significance of t(1;19). PATIENTS AND METHODS Cytogenetic data were accepted for 1,322 children ( 〈 21 years old) with newly diagnosed ALL enrolled between 1988 and 1994 on risk-adjusted studies of the Children's Cancer Group (CCG). Forty-seven patients (3.6%) were t(1;19) positive (+); 1,275 (96.4%) were t(1;19) negative (-). Clinical characteristics and treatment outcome were compared using standard methods. RESULTS Translocation (1;19)+ patients were more likely than t(1;19)- patients to be 10 years of age or greater (P 〈 .001) or CD10+ CD19+ CD34- (P 〈 .0001), or nonwhite (P = .02). Patients with a balanced t(1;19) were less likely to be hyperdiploid than patients with an unbalanced der(19)t(1;19). Event-free survival (EFS) was similar for the overall group of t(1;19)+ and t(1;19)- patients, with 4-year estimates of 69.5% (SD, 6.8%) and 74.8% (SD, 1.3%; P = .48), respectively. However, patients with unbalanced der(19)t(1;19) had significantly better outcomes than patients with balanced t(1;19): 4-year EFS were 80.6% (SD, 7.1%) and 41.7% (SD, 13.5%), respectively (P = .003). These differences were maintained within the individual studies analyses and after exclusion of t(1;19)+ patients whose cells were hyperdiploid with more than 50 chromosomes. CONCLUSION The overall group of t(1;19)+ patients, as well as the subgroup with an unbalanced der(19)+ (1;19) had outcomes similar to that of t(1;19)- patients, whereas patients with balanced t(1;19) had poorer outcomes. Thus, although the overall prognostic significance of t(1;19) has been obviated by contemporary risk-adjusted protocols, the balanced t(1;19) translocation remains an adverse prognostic factor.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1998.16.2.527
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1998
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome
    Springer Science and Business Media LLC ; 2004
    In:  Leukemia Vol. 18, No. 4 ( 2004-04-01), p. 693-702
    Details
    In: Leukemia, Springer Science and Business Media LLC, Vol. 18, No. 4 ( 2004-04-01), p. 693-702
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
    URL: Article
    DOI: 10.1038/sj.leu.2403324
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2004
    detail.hit.zdb_id: 2008023-2
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  • 4
    Online Resource
    Online Resource
    Pharmacokinetics and pharmacodynamics of asparaginases in antibody-negative pediatric patients with higher risk acute lymphoblastic leukemia (ALL): A report from CCG-1961
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 18_suppl ( 2006-06-20), p. 9027-9027
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 18_suppl ( 2006-06-20), p. 9027-9027
    Abstract: 9027 Background: Asparaginase (ASNase) induces apoptosis in ALL lymphoblasts by depleting cells of extracellular asparagine (ASN) and possibly glutamine (GLN). On CCG-1961 [Seibel NL et al. Blood 2003; 102(11): 224a (abstract #787)], all p atients (pts) received 9 doses of native E.coli-ASNase in induction (IND). Pts with rapid early response (marrow blasts 〈 25% on Day 7, RER) were randomized to standard intensity therapy and received native ASNase thereafter or to stronger intensity therapy and received PEG-ASNase post induction. All pts with slow early response (marrow blasts ≥ 25% on Day 7, SER) received PEG-ASNase after induction. Pts with clinical allergy to E.coli-ASNase were switched to Erwinase. Methods: Anti-ASNase Antibody (Ab) titers were assayed at the end of IND, prior to Delayed Intensification #1 and prior to starting Maintenance. Amino acid levels were measured in 430 sera from 187 patients with measurable ASNase activity. Results: Population pharmacokinetics (PK) and pharmacodynamics (PD) of the ASNase formulations demonstrated half-lives of native ASNase (6000 IU/m 2 ): 30 hours, PEG-ASNase (2500 IU/m 2 ): 156 hours, and Erwinase (6000 IU/m 2 ): 18 hours. Subsequent exposures to either formulation resulted in increased activity with moderate prolongation of the elimination half-lives. One-hundred forty-two sera from 70 patients with ASNase activity between 0.03 and 1.11 IU/ml, had a mean ± SDEV ASNase activity, ASN levels, and GLN levels of 0.21 ± 0.23 IU/ml, 14.6 ± 17.7 μM, and 300.4 ± 233.8 μM, respectively; with median values of 0.11 IU/ml (range: 0.03–1.114 IU/ml), 4.7 μM (range: 0.38 - 81.34 μΜ), and 270.2 μM (range: 5.3 - 1189.1 μM), respectively. TTEST analyses linked higher ASNase activity with lower ASN levels and greater % ASN deamination. Higher ASNase activity did not assure greater GLN depletion. Conclusions: A sigmoid relationship between ASNase levels and % ASN deamination showed that activity of 0.41 ± 0.24 IU/ml (mean ± SDEV) provided 93% ± 13% ASN deamination. Therefore, 〉 90% ASN deamination required ASNase 〉 0.4 IU/ml. Kaplan-Meier analyses are pending. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2006.24.18_suppl.9027
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Incidence of adverse reactions to post-induction asparaginase (ASP) therapy in children and adolescents with high-risk acute lymphoblastic leukemia (ALL): A report from the Children’s Oncology Group Study CCG-1961
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 15_suppl ( 2008-05-20), p. 10021-10021
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 15_suppl ( 2008-05-20), p. 10021-10021
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2008.26.15_suppl.10021
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Significance of HOX11L2/TLX3 expression in children with T-cell acute lymphoblastic leukemia treated on Children's Cancer Group protocols
    Springer Science and Business Media LLC ; 2005
    In:  Leukemia Vol. 19, No. 9 ( 2005-09-01), p. 1705-1708
    Details
    In: Leukemia, Springer Science and Business Media LLC, Vol. 19, No. 9 ( 2005-09-01), p. 1705-1708
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
    URL: Article
    DOI: 10.1038/sj.leu.2403834
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2005
    detail.hit.zdb_id: 2008023-2
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  • 7
    Online Resource
    Online Resource
    Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.
    American Society of Clinical Oncology (ASCO) ; 1998
    In:  Journal of Clinical Oncology Vol. 16, No. 4 ( 1998-04), p. 1270-1278
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 16, No. 4 ( 1998-04), p. 1270-1278
    Abstract: Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure. The current study was conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients. MATERIALS AND METHODS The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data. Outcome analyses used standard life-table methods. RESULTS Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review. The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66) karyotypes; modal chromosome number was not a significant prognostic factor. Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes. CONCLUSION Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1998.16.4.1270
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1998
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group.
    American Society of Clinical Oncology (ASCO) ; 1991
    In:  Journal of Clinical Oncology Vol. 9, No. 6 ( 1991-06), p. 1012-1021
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 9, No. 6 ( 1991-06), p. 1012-1021
    Abstract: On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1991.9.6.1012
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1991
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    The effect of initial management of hyperleukocytosis on early complications and outcome of children with acute lymphoblastic leukemia.
    American Society of Clinical Oncology (ASCO) ; 1988
    In:  Journal of Clinical Oncology Vol. 6, No. 9 ( 1988-09), p. 1425-1432
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 6, No. 9 ( 1988-09), p. 1425-1432
    Abstract: Data were collected from 124 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and WBC greater than 200,000/microL seen at institutions affiliated with the Children's Cancer Study Group (CCSG) from April 1981 to May 1983. The presenting characteristics, initial management, early complications, and outcome were reviewed. All the children received vigorous intravenous (IV) hydration, alkalinization of the urine, and allopurinol. Thirty-two patients were started on full therapy with no additional measure. One or more special measures believed to reduce the complications of leukostasis and blast cell lysis were administered to 92 patients as follows: small initial doses of prednisone, 63; emergency cranial irradiation, 26; exchange transfusion, 21; and leukopheresis, 19. The incidence of CNS hemorrhage was only 3% (4/124). Seven patients expired during induction and four failed to achieve a remission by day 28. Nineteen patients (15%) had documented bacterial or fungal sepsis. Mild to moderate electrolyte abnormalities occurred in 29 patients: three patients required renal dialysis. Pretreatment with small doses of prednisone did not decrease the incidence of electrolyte abnormalities in those patients when compared with patients who received full chemotherapy. The event-free survival (EFS) for the 106 patients treated on one of the three intensive pilot studies is 55% at 36 months. On multivariate analysis the two significant adverse prognostic factors were massive splenomegaly (P = .02) and WBC count greater than 600,000/microL (P = .05). In conclusion, in patients with hyperleukocytosis the complications of blast cell lysis and leukostasis were manageable with acceptable morbidity and minimal mortality in a group of patients treated with vigorous hydration, allopurinol, and alkalinization of the urine before beginning chemotherapy. Selected patients with severe hyperuricemia and renal dysfunction may benefit from leukopheresis. No beneficial role was demonstrated for the use of small initial doses of prednisone or emergency cranial irradiation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1988.6.9.1425
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1988
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: a report from the Children's Cancer Group.
    American Society of Clinical Oncology (ASCO) ; 1997
    In:  Journal of Clinical Oncology Vol. 15, No. 6 ( 1997-06), p. 2222-2230
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 15, No. 6 ( 1997-06), p. 2222-2230
    Abstract: Compared with previous Children's Cancer Group (CCG) acute lymphoblastic leukemia (ALL) trials, therapy based on the Berlin-Frankfurt-Munster (BFM) 76 trial has effected an improvement in event-free survival (EFS). In an attempt to improve EFS further, CCG investigators formulated an augmented BFM (A-BFM) regimen that provides prolonged, intensified postinduction chemotherapy relative to the CCG-modified BFM regimen. PATIENTS AND METHODS We tested A-BFM in 101 patients with ALL and unfavorable presenting features that showed slow early response (SER) to induction therapy who attained remission on day 28. Their outcome was compared with that of 251 concurrent patients with unfavorable presenting features, a rapid early response to therapy (RER), and remission by day 28, treated with CCG-BFM with or without cranial radiation (CRT). RESULTS The 4-year EFS rate from the end of induction for SER patients treated with A-BFM was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission beyond 5 years. Vincristine (VCR) neurotoxicity developed in 50% of patients, but was rarely debilitating. Allergies to Escherichia coli L-asparaginase (L-ASP) occurred in 35% of patients. Avascular necrosis of bone (AVN) developed in 9% of patients. In comparison, a concurrent RER group treated with standard BFM +/- CRT had a 4-year EFS rate of 73.1% +/- 4.6%. CONCLUSION The toxicity of A-BFM is significant, but acceptable. Compared with historical control SER patients treated with CCG-modified BFM, A-BFM therapy appears to produce a significant improvement in EFS. This is the first study to show that intensive chemotherapy, as given in the A-BFM regimen, can abrogate the adverse prognostic significance of SER.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1997.15.6.2222
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1997
    detail.hit.zdb_id: 2005181-5
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