Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91

Pérel, Yves; Auvrignon, Anne; Leblanc, Thierry; Vannier, Jean‐Pierre; Gautier, Michel; Nelken, Brigitte; Gandemer, Virginie; Schmitt, Claudine; Lamagnere, J. P.; Lumley, L. De; Bader-Meunier, Brigitte; Couillaud, Gérard; Schaison, G; Landman‐Parker, Judith; Thuret, Isabelle; Dalle, Jean‐Hugues; Baruchel, André

doi:10.1200/jco.2002.07.300

Cited by 77 publications

(46 citation statements)

References 37 publications

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“…3 Overall compliance of patients for randomization was 68.6%; 70 were randomized and evaluable (36 with and 34 without MT). The pretreatment characteristics of patients in the two randomized arms were similar.…”

Section: Potential Biases or Confounding Variables (Randomized Study)mentioning

confidence: 99%

“…The two consolidation courses were previously described 3 and are summarized in Figure 1 and Table 2; infants received only the cytarabine-asparaginase combination.…”

Section: Postremission Therapymentioning

confidence: 99%

“…The results of this randomized study have been published previously. 3 Results are now updated and described in a higher number of patients. LAME SP: From 1997 to 1998, the use of timed-sequencing of the highly intensive LAME induction chemotherapy (LAME SP) was investigated in a LAME sequential pilot study and the results are reported herein.…”

mentioning

confidence: 99%

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Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Pérel¹,

Auvrignon²,

Leblanc³

et al. 2005

Leukemia

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From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucé mie Aiguë Myé loblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 6074 and 4874%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 5274% for non-allografted patients and 5777% for allografted patients (P ¼ NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MTÀ) than in patients randomized for MT (77.678 vs 5978%; P ¼ 0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.

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Section: Potential Biases or Confounding Variables (Randomized Study)mentioning

confidence: 99%

“…The two consolidation courses were previously described 3 and are summarized in Figure 1 and Table 2; infants received only the cytarabine-asparaginase combination.…”

Section: Postremission Therapymentioning

confidence: 99%

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Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Pérel¹,

Auvrignon²,

Leblanc³

et al. 2005

Leukemia

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“…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%

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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“…L-Asparaginase from Tetrahymena pyriformis suppresses the growth of breast tumours [6]. Recently, attempts to use bacterial L-asparaginases in the treatment of myeloblastic leukaemia [7], Hodgkin and non-Hodgkin diseases [8], myelosarcoma and multiple myeloma [9] have been reported.…”

Section: Introductionmentioning

confidence: 99%

One‐step purification and kinetic properties of the recombinant l‐asparaginase from Erwinia carotovora

Krasotkina

Borisova

Gervaziev

et al. 2004

Biotech and App Biochem

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ECAR-LANS, the recombinant L-asparaginase fromErwinia carotovora, is a prospective therapeutic enzyme for leukaemia treatment. An efficient and economical scheme was developed for the purification, cloning and expression in Eschericha coli of ECAR-LANS. More than 90 % purity, complemented with 72 % active enzyme recovery, was achieved with a single chromatographic purification step. The activity of purified L-asparaginase was 630 i.u./mg. The ECAR-LANS K m value was 98 × 10 −6 M for the main physiological substrate L-Asn and 3400 × 10 −6 M for L-Gln. ECAR-LANS was found to have low relative glutaminase activity (1.2 %) at physiological concentrations of L-Asn and L-Gln in blood. Kinetic studies of ECAR-LANS showed that the recombinant asparaginase combined the main advantages of Erw. chrysanthemi and E. coli L-asparaginases II, currently used in the treatment of acute lymphoblastic leukaemia.

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Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91

Cited by 77 publications

References 37 publications

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Improved treatment results for childhood acute myeloid leukemia in Taiwan

One‐step purification and kinetic properties of the recombinant l‐asparaginase from Erwinia carotovora

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