A new combination of two intercalating agents (mitoxantrone + daunomycin) in adult refractory acute leukemia: the DON protocol

Laporte, Jean; Gorin, Norbert‐Claude; Lemonnier, Marie-Paule; Isnard, F; Najman, A

doi:10.1007/bf00254243

Cited by 7 publications

(3 citation statements)

References 11 publications

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“…The nature of induction and consolidation chemotherapies administered to patients with AML varied because the majority had been referred to our institution for ABMT. All patients in CR1 received two or three consolidation courses of cytosine arabinoside (ARAC), daunorubicin, rubidomicin, etoposide or noventrone ( Laporte et al , 1988 ). Patients with ALL were enrolled in two trials (LALA 96 and GOELAL 2).…”

Section: Methodsmentioning

confidence: 99%

Quantitative and qualitative alterations of long‐term culture‐initiating cells in patients with acute leukaemia in complete remission

Yao¹,

Bouchet²,

Harnois³

et al. 1998

Br J Haematol

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Summary. Bone marrow (BM) samples from 24 patients with acute leukaemia (AML 17, ALL seven) in first complete remission were compared to samples from 10 normal donors with regard to their content in long-term culture-initiating cells (LTC-IC) as assessed by a limiting dilution assay and the clonogeneic capacity of these cells, in order to determine whether remission marrow cells displayed any specific defect at the primitive stem cell level. The frequency of LTC-IC in the whole patient group was 1 in 3487 Ϯ 3125 mononuclear cells (MNC) as compared to 1 in 794 Ϯ 492 MNC in normal controls (P ¼ 0·0009), with no difference between AML and ALL. Moreover, the clonogeneic capacities were 2·66 Ϯ 0·7 (range 1·8-1·6) and 4·0 Ϯ 1·6 (range 2·2-7·9) CFC per LTC-IC in patients and controls respectively (P ¼ 0·0015). These quantitative and qualitative defects were aggravated by treatment with mafosfamide at a dose of 50 mg/10 7 MNC/ ml, where the mean recovery of LTC-IC after in vitro purging was 42%. In nine patients autografted with purged marrow following high-dose radiochemotherapy, no correlation could be detected between the dose of LTC-IC (mean 6742 Ϯ 7877/kg) and the kinetics of recovery of haemopoiesis. We concluded that, in acute leukaemia patients in complete remission, the presumably normal residual stem cell pool was not only quantitatively diminished but also qualitatively altered in its capacity to give rise to clonogeneic progenitor cells.

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Section: Methodsmentioning

confidence: 99%

Quantitative and qualitative alterations of long‐term culture‐initiating cells in patients with acute leukaemia in complete remission

Yao¹,

Bouchet²,

Harnois³

et al. 1998

Br J Haematol

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“…This treatment which was initially assessed with success in refractory AML or in AML in relapse 8 does not include cytarabine and consists of vincristine on day 1 with a combination of two anthracyclines (daunorubicin 45 mg/m 2 /day on days 2, 3 and 4 and mitoxantrone, 12 mg/m 2 /day from days 2 to 6). In case of blast cell persistence on bone marrow aspiration on day 15, a second course of cytarabine at intermediate dosage and amsacrine was given.…”

Section: Treatmentmentioning

confidence: 99%

“…In an effort to increase the remission rate and maintain the remission status until intensification, we increased doses of anthracyclines and introduced intermediate doses of aracytine, respectively. From 1989, we used a new first-line induction regimen effective in refractory AML, the DON, 8 which we previously developed for resistant disease, followed by two courses of consolidation before marrow collection. The first one combined intermediate-dose cytarabine and amsacrine, the second, cytarabine and etoposide.…”

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confidence: 99%

Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution

Isnard

Guiguet

Laporte

et al. 2001

Bone Marrow Transplant

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Summary:A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 ± 7% vs 32 ؎ 8%, P = 0.04) and overall survival (OS) (53 ± 6% vs 30 ± 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.

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Mitoxantrone in the treatment of acute myelogenous leukemia: a review

Thomas

Archimbaud

1997

Hematol Cell Ther

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Mitoxantrone is an intravenous anthracenedione structurally related to the anthracycline antibiotics. This drug has been used for several years in the treatment of acute myelogenous leukemia (AML). Its use has been based on its pharmacological properties, its incomplete cross-resistance with other intercalating agents, and its better tolerance as predicted by preclinical studies. Various treatment schedules, using mitoxantrone alone and in combination with other antileukemic agents, have been used in clinical trials. Complete remission (CR) rates ranged from 14 to 44% in refractory AML and from 46 to 79% in relapsed patients. Although a superiority of mitoxantrone over anthracyclines has not been clearly demonstrated in newly diagnosed patients, mitoxantrone is now recognized as a useful drug in first line therapy. The tolerability profile of mitoxantrone indicates that it offers patients an acceptable quality of life compared with standard treatment regimens, and could be a good alternative to the anthracyclines. The development of new therapeutic concepts aiming at an optimization of its use is now in process and first results are promising.

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A new combination of two intercalating agents (mitoxantrone + daunomycin) in adult refractory acute leukemia: the DON protocol

Cited by 7 publications

References 11 publications

Quantitative and qualitative alterations of long‐term culture‐initiating cells in patients with acute leukaemia in complete remission

Quantitative and qualitative alterations of long‐term culture‐initiating cells in patients with acute leukaemia in complete remission

Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution

Mitoxantrone in the treatment of acute myelogenous leukemia: a review

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