Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group.

Löwenberg, Bob; Suciu, Stefan; Archimbaud, E; Haak, H. L.; Stryckmans, Pierre; Cataldo, Ralph; Dekker, A. W.; Berneman, Zwi; Thyss, A.; Lelie, J. Van Der; Sonneveld, Pieter; Visani, Giuseppe; Fillet, Georges; Hayat, M.; Hagemeijer, Anne; Solbu, G.; Zittoun, R

doi:10.1200/jco.1998.16.3.872

Cited by 258 publications

(151 citation statements)

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“…In the effort to improve results, the standard two-drug induction approach has been varied many times in the last 15 years as regards intensity, duration and combination. [33][34][35][36] Addition of a third drug has resulted in contradictory effects. However, employment of high-dose cytarabine seems to improve outcome, 7,8,21,24,[37][38][39] without affecting the remission rates.…”

Section: Figurementioning

confidence: 99%

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

et al. 2001

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We studied the impact of cytogenetics and kind of induction/consolidation therapy on 848 adult acute myeloid leukemia (AML) patients (age 15-83). The patients received three types of induction/consolidation regimen: standard (daunorubicin and cytosine arabinoside (3/7); two cycles); intensive (idarubicin, cytosine arabinoside and etoposide (ICE), plus mitoxantrone and intermediate-dose Ara-C (NOVIA)); and low-dose (low-dose cytosine arabinoside). CR patients under 60 years of age, if an HLA-identical donor was available received allogeneic stem cell transplantation (allo-SCT); otherwise, as part of the program, they underwent autologous (auto)-SCT. CR rates significantly associated with 'favorable' (inv(16), t(8;21)), 'intermediate' ('no abnormality', abn(11q23), +8, del(7q)) and 'unfavorable' (del (5q), −7, abn(3)(q21q26), t(6;9), 'complex' (more than three unrelated cytogenetic abnormalities)) karyotypes (88% vs 65% vs 36%, respectively; P = 0.0001). These trends were confirmed in all age groups. On therapeutic grounds, intensive induction did not determine significant increases of CR rates in any of the considered groups, with respect to standard induction. Low-dose induction was associated with significantly lower CR rates. Considering disease-free survival (DFS), multivariate analysis of the factors examined (including karyotype grouping) showed that only age Ͼ60 years significantly affected outcome. However, in cases where intensive induction was adopted, 'favorable' karyotype was significantly related to longer DFS (P = 0.04). This was mainly due to the favorable outcome of t(8;21) patients treated with intensive induction. Patients receiving allo-SCT had significantly longer DFS (P = 0.005); in particular, allo-SCT significantly improved DFS in the 'favorable' and 'intermediate' groups (P = 0.04 and P = 0.048, respectively). In conclusion our study could provide some guidelines for AML therapy: (1) patients in the 'favorable' karyotype group seem to have a longer DFS when treated with an intensive induction/consolidation regimen, adopted before auto-SCT instead of standard induction; this underlines the importance of reinforcement of chemotherapy, not necessarily based on repeated high-dose AraC cycles. Allo-SCT, independently of induction/consolidation therapy, should be considered an alternative treatment; (2) patients in the 'intermediate' karyotype group should receive allo-SCT; (3) patients in the 'unfavorable' karyotype group should be treated using investigational chemotherapy, considering that even allo-SCT cannot provide a significantly longer DFS, but only a trend to a better prognosis. Leukemia (2001) 15, 903-909.

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Section: Figurementioning

confidence: 99%

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

et al. 2001

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“…When treated with conventional chemotherapy, these older patients have a 20% 2-year and 10% 5-year survival. [2][3][4][5][6][7][8] These disappointing outcomes reflect an increased frequency of poor-risk cytogenetics, a higher incidence of antecedent myelodysplasia, higher MDR1 protein expression and a limited ability to tolerate aggressive chemotherapy. 9,10 Harnessing the immune effect 11 of allogeneic hemopoietic stem cell transplantation (SCT) may improve outcome in this resistant disease, but many older patients are unsuited to conventional SCT because of increased transplant-related mortality.…”

Section: Introductionmentioning

confidence: 99%

Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation (RISCT) using antilymphocyte antibodies in patients with high-risk acute myeloid leukemia (AML)

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et al. 2006

Bone Marrow Transplant

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“…It is noteworthy that DSF and survival results in both groups of the present study were comparable to those reported for other intensive treatment regimens in elderly AML pts. [2][3][4][5][6][7][8][9]22 This holds also true when considering all pts who reached CR or all pts registered.…”

Section: Discussionmentioning

confidence: 98%

“…In most studies, elderly AML pts receive one to three intravenous consolidation courses with reduced dosages, sometimes followed by prolonged maintenance. [5][6][7] In general, prolonged post-remission therapy does not seem to improve survival compared to short post-remission consisting of 2-3 consolidation courses only. 8 In view of the high relapse rate in older AML adults, we explored a non-infusional post-remission therapy.…”

Section: Introductionmentioning

confidence: 99%

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial

et al. 2006

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In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P ¼ 0.15, hazard ratio (HR) ¼ 1.18, 95% confidence interval (CI) 0.94-1.49) -primary end point -and survival (median 15.7 vs 17.8 months, P ¼ 0.19, HR ¼ 1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P ¼ 0.001) and diarrhea (10 vs 4%; P ¼ 0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery 420 Â 10 9 /l (median: 19 vs 23 days; P ¼ 0.02) and duration of hospitalization (mean: 15 vs 27 days; Po0.0001) was shorter. The 'noninfusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.

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Abstract: In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.

Cited by 258 publications

References 20 publications

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation (RISCT) using antilymphocyte antibodies in patients with high-risk acute myeloid leukemia (AML)

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial

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