High-dose cytosine arabinoside and mitoxantrone: A highly effective regimen in refractory acute myeloid leukemia

Hiddemann, Wolfgang; Kreutzmann, H.; Straif, Kurt; Wd, Ludwig; Donhuijsen-Ant, R.; Lengfelder, Eva; Büchner, Th.

doi:10.1007/bf02580196

Cited by 44 publications

(59 citation statements)

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“…In these trials, CR rates ranged from 34 to 58% vs 23 to 66% for HD-AraC vs ID-AraC and failure from NR was reported in 13 to 39% vs 17 to 55% of cases while early deaths occurred in 7 to 33% vs 9 to 37%. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] As for the present study, mucositis and diarrhoea were reported to occur less frequently during ID-AraC while central nervous system toxicity was limited to patients receiving HD-AraC. The hematologic toxicities encountered during the abovementioned trials did not depend on the dose level of AraC (neutropenia 25 to 28 days vs 19 to 33 days).…”

Section: Discussionmentioning

confidence: 71%

Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison

et al. 1998

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(ED)). In patients younger than 60 years the higher dose level resulted in a significant reduction of NR (12% vs 31%; ordinal 2 test: P = 0.01) but also a higher rate of ED (32% vs 17%) thus leading to a marginally higher CR rate only (52% vs 45%). Within the subgroup of patients with refractory AML the tendency towards a higher CR rate after HD-AraC was more pronounced (46% vs 26%; P = 0.045). In patients older than 60 years, corresponding though less evident differences were observed with a higher rate of NR in the lower dose group (26% vs 16%) and ED occurring more frequently after higher doses (36% vs 26%). These data indicate that HD-AraC reveals a significantly higher antileukemic efficacy than ID-AraC as expressed by a significant reduction of failure from NR. This advantage, however, does not fully translate into an increase in remission rate due to a higher incidence of ED after HD-AraC predominantly from uncontrolled infections. In order to take full advantage of the higher antileukemic activity of HD-AraC an improvement of supportive care and infection control is warranted.

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Section: Discussionmentioning

confidence: 71%

Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison

et al. 1998

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“…14 HD ara-C and mitoxantrone are effective drugs in relapsed/refractory AML and APL. 24,25 For time intensification, the second induction cycle was administered after a median Table 4 Toxicities WHO Grade X3 and APL differentiation syndrome according to therapy and initial WBC count All patients WBC o10 Â 10 9 /l WBC 10 Â 10 9 /l or more Comparison according to initial WBC count o or X10 Â 10 9 /l. n, number of patients with toxicity WHO Grade X3 or APL differentiation syndrome/number of documented patients.…”

Section: Discussionmentioning

confidence: 99%

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

et al. 2009

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The objective of this study for newly diagnosed acute promyelocytic Leukemia (APL) was to evaluate the efficacy of an intensified double induction chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA) followed by consolidation and 3 years maintenance therapy. In contrast to APL studies stratifying therapy according to pretreatment white blood cell (WBC) count o and X10 Â 10 9 /l (low/intermediate and high risk according to the Sanz score), our patients received uniform therapy. From 1994 to 2005, 142 patients (age, 16-60 years) were enrolled. In the low/intermediate (n ¼ 105) vs high (n ¼ 37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of induction death were 4.8 vs 16.2% (P ¼ 0.05) and of molecular remission were 87.5 vs 91.3% (P ¼ 1). Long-term overall survival was 84.4 vs 73.0% (P ¼ 0.12), event free survival was 78.3 vs 67.3% (P ¼ 0.11), relapse free survival was 82.1 vs 80.0% (P ¼ 0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P ¼ 0.46). No relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy including HD ara-C followed by prolonged maintenance therapy reduced the relapse risk in high risk patients. Pretreatment WBC count X10 Â 10 9 /l count was no relevant prognostic factor for relapse.

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“…2 Another crucial development is the introduction of high-dose Ara-C (HDAra-C) in either the postremission or induction phase of therapy, for both adults 3,4 and children 5 with AML. The beneficial effect of HDAra-C during postremission therapy was first demonstrated by the Cancer and Leukemia Group B, 4 while Hiddemann et al 6 reported the effectiveness of HDAra-C in combination with mixtoxantrone (HAM) in adults with refractory AML. Other innovations contributing to an improved outcome in AML were described in numerous recent reports.…”

Section: Introductionmentioning

confidence: 99%

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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High-dose cytosine arabinoside and mitoxantrone: A highly effective regimen in refractory acute myeloid leukemia

Cited by 44 publications

References 0 publications

Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison

Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

Improved treatment results for childhood acute myeloid leukemia in Taiwan

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