Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study

Ohtake, Shigeki; Miyawaki, Shuichi; Fujita, Hiroyuki; Kiyoi, Hitoshi; Shinagawa, Katsuji; Usui, Noriko; Okumura, Hirokazu; Miyamura, Koichi; Nakaseko, Chiaki; Miyazaki, Yasushi; Fujieda, Atsushi; Nagai, Tadashi; Yamane, Takahisa; Taniwaki, Masafumi; Takahashi, Masatomo; Yagasaki, Fumiharu; Kimura, Yukihiko; Asou, Norio; Sakamaki, Hisashi; Handa, Hiroshi; Honda, Sumihisa; Ohnishi, Kazunori; Naoe, Tomoki; Ohno, Ryuzo

doi:10.1182/blood-2010-03-273243

Cited by 216 publications

(157 citation statements)

References 38 publications

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“…94% of patients actually received more than 90% of the intended FLAI-5 dose (98/105), and that 89.2% of patients received more than 90% of the drug dosage that was planned for the second induction course (74/83) confirms the good feasibility of our induction program. The median overall Idarubicin dosage administered in the induction phases is higher compared to what was planned in the MRC trial (66 mg/m 2 vs. 48 mg/m 2 ) and rather similar to the dose of 72 mg/ m 2 indicated by earlier reports as the optimal dose [39,40]. Patients in our series who completed the whole program of therapy at the scheduled times displayed the best outcomes, i.e.…”

Section: Discussionmentioning

confidence: 64%

High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year, single‐center experience in younger, non M3 AML patients

et al. 2016

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About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m 2 (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m 2 per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher antileukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C 1 Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity.

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Section: Discussionmentioning

confidence: 64%

High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year, single‐center experience in younger, non M3 AML patients

et al. 2016

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“…Cytogenetic subgroups were classified as favorable, intermediate and adverse risk according to a largely accepted classification system as follows: (25) Treatment protocols. Two hundred and sixty patients who were eligible for intensive chemotherapy were treated according to the Japan Adult Leukemia Study Group (JALSG) treatment protocols (JALSG AML92, (26) AML95, (27) AML97 (28) or AML201 (29) ). All protocols consisted of single induction therapy with anthracycline (daunorubicin or idarubicine) plus cytarabine or enocitabine and were followed by three or four courses of consolidation therapy.…”

Section: Methodsmentioning

confidence: 99%

Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia

et al. 2012

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To investigate the clinical significance of granulocytic sarcoma (GS) in adults with acute myeloid leukemia (AML), 434 consecutive patients with AML were analyzed retrospectively. Forty-five patients (10.4%) with GS at diagnosis were younger (P < 0.001), presented with higher white blood cell counts (P = 0.03) and were more likely to conform to French-American-British M4 (P = 0.001) and M5 (P = 0.045) classifications than those without GS. In contrast, no significant difference in frequency of cytogenetic abnormalities was found between the GS and non-GS groups. Treatment outcomes in 260 patients (40 with GS) who underwent intensive chemotherapy, excluding patients with acute promyelocytic leukemia, were investigated. Complete remission rates did not differ significantly between the GS and non-GS groups (75.0% vs 79.1%; P = 0.192, respectively) or the 5-year overall survival (OS) rates (39.9% vs 38.7%; P = 0.749, respectively). However, the GS group had a significantly higher relapse rate than the non-GS group (74.2% vs 55.3%; P = 0.048) and a significantly lower 5-year disease-free survival rate (8.2% vs 25.7%, respectively; P = 0.005). When considered together with the results of multivariate analysis, which identified the presence of GS as an independent predictor for disease-free survival time, these findings indicate that GS might identify a high-risk subset of patients with AML. (Cancer Sci 2012; 103: 1513-1517 G ranulocytic sarcoma (GS), a rare extramedullary tumor composed of malignant granulocytic precursor cells that affects 3-9% of patients diagnosed with acute myeloid leukemia (AML), (1)(2)(3) occurs concomitantly with or after a diagnosis of AML. Granulocytic sarcoma can occur in any organ and common sites are bones, lymph nodes, soft tissues and skin. (4) Other organs, including the brain, (5,6) orbit (7,8) and genitourinary system, (9,10) are infrequently affected by GS. Such variation in its site of occurrence complicates accurate diagnosis of GS, and, moreover, the low incidence of GS has impeded establishment of the clinical characteristics of patients with GS. Several studies have reported that specific factors, including French-American-British (FAB) M4 and M5 classification (11,12) and the expression of CD56 (13,14) or T-cell antigens (CD2, CD4 and CD7) (15,16) on leukemia cells, are associated with GS, while others have identified an association between GS and t(8;21) (17,18) or inv(16). (19,20) Establishment of the clinical characteristics of GS has been further impeded by the mixed results obtained by several studies that investigated the prognosis of GS in limited subpopulations of AML patients. Byrd et al. (21) found that GS was associated with unfavorable outcomes and a shorter survival time (median 5.4 months with GS vs 59.5 months without GS) among AML patients carrying t(8;21), whereas Felice et al. (22) argued that GS had no adverse prognostic impact on AML patients carrying t(8;21). In light of these discrepant findings, this study aimed to clarify the clinical significance of GS...

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“…Therefore, the total doses of DNR administered during the first course of induction therapy were 240-280 mg/m 2 given for more than 5-7 days, which was more than the conventional dose of 40-60 mg/m 2 given for 3 days. As there had been no direct comparison between a high dose of DNR and the standard dose of IDR (12 mg/m 2 ), we prospectively compared IDR (12 mg/m 2 for 3 days) with DNR (50 mg/m 2 for 5 days), in combination with Ara-C (100 mg/m 2 for 7 days), in the AML201 study [12]. Of the 1064 patients registered, 1057 patients were evaluable.…”

Section: Induction Therapymentioning

confidence: 99%

Clinical studies of acute myeloid leukemia in the Japan Adult Leukemia Study Group

Miyawaki

2012

Int J Hematol

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Acute myeloid leukemia (AML) is the most common adult leukemia in Japan. The treatment for AML consists of induction, consolidation, and maintenance therapies. To improve outcomes in the treatment of AML, the Japan Adult Leukemia Study Group has conducted six studies in AML patients aged 15-64 years since 1987. In AML201 study, IDR (12 mg/m 2 /day for 3 days) or DNR (50 mg/m 2 /day for 5 days) in combination with Ara-C (100 mg/m 2 /day continuous infusion for 7 days) was established as the standard induction therapy, and four courses of combination chemotherapy using non-crossresistant agents for non-core binding factor (CBF) AML or three courses of high-dose Ara-C for CBF AML was established as the standard consolidation therapy. The AML97 study showed that allo-HSCT from an HLAidentical sibling donor reduced relapse incidence and improved disease-free survival (DFS), but did not significantly impact overall survival (OS) in poor or intermediate risk patients. Despite these studies by JALSG, only about one-third of AML patients remain free of disease for more than 7 years. The JALSG is now conducting the AML209 study to adapt individual therapies according to genetic alterations.

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Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study

Cited by 216 publications

References 38 publications

High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year, single‐center experience in younger, non M3 AML patients

High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year, single‐center experience in younger, non M3 AML patients

Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia

Clinical studies of acute myeloid leukemia in the Japan Adult Leukemia Study Group

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