Idarubicin/Cytosine Arabinoside and Mitoxantrone/Etoposide with rhGM-CSF Priming for De Novo Acute Myelogenous Leukemia

Haas, Rainer; Döhner, Hartmut; Ehrhardt, Rogério de Assunção; Goldschmidt, H. M. J.; Witt, Barbara; Huberts, H.; Goebel, Matthias; Valle, Francesco del; Hünstein, W.

doi:10.1007/978-3-642-78350-0_103

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…[18][19][20][21][22][23][24][25][26][27][28][29] In randomised trials it has been compared with daunorubicin in the treatment of de novo adult AML, and has been shown to be associated with increased remission rates and survival. [30][31][32] With respect to toxicity, idarubicin appears to be qualitatively similar to other anthracyclines, although some studies suggest it may be more myelosuppressive and produce greater gastrointestinal toxicity.…”

Section: Discussionmentioning

confidence: 99%

Use of idarubicin in pre-transplant conditioning in children with high-risk acute leukaemia

Lawson

Williams

Darbyshire

1999

Bone Marrow Transplant

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Summary:The major cause of treatment failure following allogeneic bone marrow transplantation for acute leukaemia is disease relapse. In an attempt to reduce posttransplant relapse in 33 children with high-risk acute leukaemia who received a related or unrelated bone marrow transplant, the pre-transplant conditioning regimen was intensified by the addition of idarubicin. Its toxicity and effects on survival were evaluated over a 57-month period. Toxicity, largely gastrointestinal, was increased but acceptable, and there was no specific regimen-related toxicity. Relapse rates were low (24%) in this high risk group, but mortality was increased in those receiving unrelated donor grafts, largely due to sepsis. Idarubicin does appear to have a role to play in the conditioning regimen of patients with high-risk acute leukaemia undergoing BMT, and may reduce relapse rates without increasing transplant-related mortality. Keywords: childhood acute leukaemia; idarubicin; BMT Acute leukaemias are rare in children, and represent onethird of all childhood malignancies. In children with high-risk acute leukaemia in either first or other remission, prognosis is poor. Intensive treatment including allogeneic bone marrow transplantation may offer the best chance of long-term disease-free survival.1-13 Leukaemic recurrence however, continues to play a major role in treatment failure.One possible way of reducing the probability of relapse is to further intensify the conditioning regimen prior to transplantation using anthracyclines which have proven anti-leukaemic activity, provided this approach is not associated with unacceptable toxicity and increased procedurerelated mortality. [14][15][16] Two pilot studies have demonstrated a reduction in relapse rates, improved disease-free and actuarial survival with comparable transplant-related mortality in patients receiving intensified conditioning with idarubicin prior to sibling T cell-depleted grafts when compared with historical controls. sified conditioning regimens in a heterogeneous population of patients with malignant haematological disease. They also demonstrated reduced relapse probability, increased overall and disease-free survival without increased transplant-related mortality in comparison with historical controls receiving cyclophosphamide and total body irradiation (TBI) alone, prior to a T cell-depleted graft. The toxicity of the intensified regimen was schedule-dependent and was reduced by administration of idarubicin earlier in the conditioning regimen.We report the use of an intensified conditioning regimen containing idarubicin in 33 children considered to be at high risk of leukaemic relapse. We discuss the toxicity of the regimen and its success with respect to relapse and mortality.

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Section: Discussionmentioning

confidence: 99%

Use of idarubicin in pre-transplant conditioning in children with high-risk acute leukaemia

Lawson

Williams

Darbyshire

1999

Bone Marrow Transplant

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“…Most patients are clinically refractory to chemotherapy, and polychemotherapy is not convenient. First results [39][40][41][42][43][44] with IDA in combination with cytarabine or vincristine, l-asparaginase, and prednisolone demonstrate that IDA is effective in AML patients, ALL patients, and CML patients with lymphoid blast transformation. Berman et al and Tidefelt et al for instance demonstrated that IDA can overcome P-gp-related resistance in vitro [35,36].…”

Section: Discussionmentioning

confidence: 99%

Idarubicin monotherapy in multiply pretreated leukemia patients: response in relation to P-glycoprotein expression

Nüssler

Gieseler²,

Zwierzina

et al. 1997

Annals of Hematology

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The aim of the study was to test whether fractionated (weekly) idarubicin administration to multiply pretreated leukemia patients is effective and tolerable for outpatient treatment, and whether idarubicin alone can overcome P-glycoprotein (P-gp)-related resistance. P-gp was assessed with an immunocytological technique using the monoclonal antibody 4E3.16. P-gp. expression was characterized as a percentage of P-gp-positive blasts. Additionally, the function of P-gp was determined with the rhodamine-123 (R-123) accumulation test in combination with or without verapamil and expressed as the R123 accumulation ratio. Fractionated idarubicin (12 mg/m2/week) was given to 36 acute myelogenous leukemia (AML) patients, 12 acute lymphoblastic leukemia (ALL) patients, and eight chronic myelogenous leukemia (CML) patients in blast crisis. Furthermore, 11 AML and four ALL patients were treated with fractionated daunorubicin at a dose of 50 mg/m2/week. All patients had been pretreated with drugs inducing P-gp-related resistance including daunorubicin and/or doxorubicin or vindesine (CML patients). Of 71 pretreated patients, 51 (72%) had a P-gp value between 25 and 98%. Six of these patients with increased P-gp expression had a nonpumping P-gp; four of them were CD34 positive. Of 51 patients with increased P-gp expression, 30 (59%) were CD34 positive. With regard to idarubicin monotherapy, overall response was 33/56 (59%) patients, and 23/33 (70%) responding patients showed a P-gp expression between 25 and 95%. All idarubicin-responding patients with high P-gp expression before treatment showed a clear reduction of P-gp-positive blasts. No patients with P-gp expression between 34 and 85% treated with fractionated daunorubicin showed response or reduction of P-gp-positive blasts in bone marrow. This study demonstrates that P-gp-related resistance can be overcome in multiply pretreated leukemia patients with idarubicin alone, and that the protocol used here is tolerable for outpatient treatment.

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Idarubicin/Cytosine Arabinoside and Mitoxantrone/Etoposide with rhGM-CSF Priming for De Novo Acute Myelogenous Leukemia

Cited by 2 publications

References 6 publications

Use of idarubicin in pre-transplant conditioning in children with high-risk acute leukaemia

Use of idarubicin in pre-transplant conditioning in children with high-risk acute leukaemia

Idarubicin monotherapy in multiply pretreated leukemia patients: response in relation to P-glycoprotein expression

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