Improved Treatment Results in High-Risk Pediatric Acute Myeloid Leukemia Patients After Intensification With High-Dose Cytarabine and Mitoxantrone: Results of Study Acute Myeloid Leukemia–Berlin-Frankfurt-Münster 93

Creutzig, Ursula; Ritter, J.; Zimmermann, Martin; Reinhardt, Dirk; Hermann, J; Berthold, Frank; Henze, Günter; Jürgens, Heribert; Kabisch, H; Havers, W.; Reiter, Alfred; Kluba, U; Niggli, Felix; Gadner, Helmut

doi:10.1200/jco.2001.19.10.2705

Cited by 179 publications

(136 citation statements)

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“…In study AML-BFM93, induction with idarubicin was more effective than daunorubicin in reducing the blast cells in bone marrow on day 15. 10 Moreover, meta-analysis of results from randomized trials comparing idarubicin, mitoxantrone, and daunorubicin revealed a statistically significant improvement in remission rate with idarubicin, and a trend toward a better rate with mitoxantrone compared to daunorubicin (Wheatley K. Blood, 1995;86:43; abstract). When combined with Ara-C (100 mg/m 2 / day Â 7), idarubicin was more effective than daunorubicin in remission induction.…”

Section: Discussionmentioning

confidence: 99%

“…Other innovations contributing to an improved outcome in AML were described in numerous recent reports. [7][8][9][10][11][12][13][14][15] Besides agents that increase the antileukemic efficacy of modern AML treatments, advances in molecular biology have led to the recognition of prognostically and therapeutically relevant subtypes of AML, while improved supportive care, consisting of more effective antimicrobials (especially the antifungal agents), blood component therapy, hematopoietic stem cell transplantation, and antiemetics, has prevented excessive toxic deaths due to intensive chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Improved treatment results for childhood acute myeloid leukemia in Taiwan

et al. 2005

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To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C -containing regimens for four monthly courses, and moderatedose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with alltrans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 5175.3% (s.e.) and the 5-year event-free survival 5074.8%; for APL, these were 100%, 8677.0, and 7579.8%. For the whole group, the 5-year survival was 5774.7% and the 5-year event-free survival 5474.4%. The AML-97A regimen was well tolerated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved treatment results for childhood acute myeloid leukemia in Taiwan

et al. 2005

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“…[11][12][13] Allo-SCT from a matched sibling donor was recommended for high-risk patients in CR1 only.…”

Section: First-line Treatmentmentioning

confidence: 99%

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

et al. 2010

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Relapse remains the major cause of treatment failure in pediatric acute myeloid leukemia (AML). We analyzed the clinical characteristics, treatment response to relapse treatment and overall survival (OS) of 379 children with AML relapse treated according to three consecutive frontline protocols of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87/-93/-98). Of 313 treated patients with data on remission status, 198 children (63%) achieved a second complete remission (CR2). There were no significant differences in remission rates and OS for the intensive reinduction treatment schedules used.The 5-year OS rate was 23% for the total group and 29% for patients treated with curative intent. OS rates increased with study periods from 18 to 34% (P log rank ¼ 0.012), whereas the proportion of patients receiving only palliative treatment decreased from 23 to 11% (P CMH ¼ 0.005). Late relapse, no allogeneic stem cell transplantation (SCT) in CR1, age o10 years and favorable cytogenetics were independent favorable prognostic factors for survival. Achievement of CR2 was the most important prognostic factor (OS 44 vs 3%; P log rank o0.0001). Overall, one-third of children with relapsed AML can be cured today. SCT in CR2 is recommended for most patients, although its impact on CR2 is discussed.

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“…This has been accomplished by the introduction of refined schedules of combination chemotherapy (Reiter et al, 1994;Pui and Evans, 1998;Stevens et al, 1998;Creutzig et al, 2001). As a consequence of the improved prognosis and risk-adapted treatment, the prognostic significance of a number of parameters at presentation has decreased.…”

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confidence: 99%

Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia

et al. 2003

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Bone marrow and peripheral blood samples from 362 patients with acute lymphoblastic leukaemia (ALL) proliferating cell and 90 patients with acute myeloid leukaemia (AML) were analysed for S-phase fractions, Ki67 antigen, and proliferating cell nuclear antigen expression. The S-phase fractions were correlated with in vitro drug resistance to 15 different anticancer agents. Leukaemia cells isolated from bone marrow had higher S-phase fractions than leukaemia cells isolated from peripheral blood (in initial ALL, median values resp. 6.9 and 2.7%, in initial AML resp. 5.3 and 1.3%; both Po0.01). Relapse ALL samples derived from bone marrow showed increased S-phase fractions (median 9.9%) compared with initial ALL samples (median 6.9%; Po0.01). ALL samples obtained at initial diagnosis showed higher S-phase fractions (median 6.9%) and higher Ki67 expression (median 30%) than initial AML samples (median resp. 5.3 and 14%; both Po0.05). The S-phase fractions were not related to white blood cell count, age, or gender. Within initial ALL, the S-phase fraction correlated significantly but modestly strong (r ¼ 0.3 -0.5; Po0.05) with sensitivity to antimetabolites (cytarabine, mercaptopurine, thioguanine), L-asparaginase, teniposide, and vincristine. Similar results were found within subgroups of initial ALL (nonhyperdiploid and common/precursor-B-lineage ALL). In relapsed ALL and AML such correlations were not found. In conclusion, cell proliferation differs between leukaemia subgroups and increased proliferation is associated with increased in vitro sensitivity to several anticancer agents in initial ALL.

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Improved Treatment Results in High-Risk Pediatric Acute Myeloid Leukemia Patients After Intensification With High-Dose Cytarabine and Mitoxantrone: Results of Study Acute Myeloid Leukemia–Berlin-Frankfurt-Münster 93

Abstract: Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

Cited by 179 publications

References 19 publications

Improved treatment results for childhood acute myeloid leukemia in Taiwan

Improved treatment results for childhood acute myeloid leukemia in Taiwan

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia

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