FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies

Rubia, Javier de la; Regadera, Anabel; Martı́n, Guillermo; Cervera, José; Sanz, Guillermo; Martı́nez, Jesús; Jarque, Isidro; Garcı́a, Inmaculada; Andreu, Rafael; Moscardó, Federico; Jiménez, Carmen; Mollá, Susana; Benlloch, Luis; Sanz, Miguel Á.

doi:10.1016/s0145-2126(02)00003-6

Cited by 39 publications

(10 citation statements)

References 29 publications

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“…In this setting, the formal comparison of our results to other salvage regimens of similar intensity is difficult because of the heterogeneity of included patients, which significantly influences the outcome. In most of the studies, patients with poor risk de novo AML, refractory AML and patients with early and late relapse were enrolled (6, 7, 9, 15, 21, 22, 41–43). Moreover, in contrast to our report, many other studies have only included small numbers of patients, which makes it difficult to identify and confirm the best treatment option in this poor risk group.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with primary refractory disease and with early relapses, following a CR1 of less than 6 months, have a significantly poorer response to therapy and overall outcomes in comparison to AML patients with later relapse (CR rate 10–30% vs . 40–60%) (5–9). The optimum strategy at the time of relapse or for patients with resistant disease remains uncertain.…”

mentioning

confidence: 99%

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Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G‐CSF (CLAG‐M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group

Wierzbowska

Robak

Pluta

et al. 2007

European J of Haematology

134

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G‐CSF (CLAG‐M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group

Wierzbowska

Robak

Pluta

et al. 2007

European J of Haematology

134

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“…The purine analog fludarabine, initially used in lymphoid malignancies, has shown promising results in AML. In the last 15 years, fludarabine-based induction regimens have been tested in patients with relapsed AML and, more recently, at disease onset [9,13,15,16,[20][21][22][23][24][25][26]. The rationale of fludarabine inclusion in cytarabine-containing courses is based on the synergic activity of the two drugs that has been proved both in vivo and in vitro [25][26][27].…”

Section: Methodsmentioning

confidence: 99%

Pulmonary thrombi are not detected by 3D magnetic resonance angiography in adults with sickle cell anemia and an elevated triscuspid regurgitant jet velocity

et al. 2009

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An elevated tricuspid regurgitant jet (TRJ) velocity is present in more than 30% of adults with sickle cell anemia (SCA) and is associated with a risk of death [1][2][3][4]. The contribution of pulmonary thrombi to an elevated TRJ velocity is not well defined. To evaluate the relationship between an elevated TRJ velocity and pulmonary thrombi, we performed 3D, contrast-enhanced magnetic resonance angiography (3D MRA) in nine adults with SCA. Of the six participants with an elevated TRJ velocity, 5 (83%) did not have thrombi in their pulmonary arteries. No individuals with a normal TRJ velocity had pulmonary thrombi. Based on this pilot study using 3D MRA images, thrombi are not present in large vessels in most individuals with a TRJ 2.5 m/sec, providing evidence thrombi may not significantly contribute to the pathogenesis of an elevated TRJ velocity in individuals with SCA.Pulmonary thrombi are a common etiology of pulmonary hypertension in the general population, and several autopsy studies of individuals with SCA and pulmonary hypertension have reported pulmonary thrombi [5][6][7]. Of individuals with SCA and pulmonary thrombi, 66% involve large pulmonary arteries, indicating an embolic event; however, an autopsy study of individuals with SCA and histological evidence of pulmonary hypertension (n = 20) noted thrombi in the small pulmonary arteries of 33% of individuals [6]. These autopsy studies were published prior to reports describing the risk of mortality associated with an elevated TRJ velocity and thus they examined individuals with SCA and either symptomatic pulmonary hypertension or without a diagnosis of pulmonary hypertension, but with hypertensive changes on autopsy. There have been no autopsy studies examining the pulmonary vasculature of individuals based on the mild elevations in TRJ velocity that are now recognized to be clinically significant. Therefore, the contribution of pulmonary thrombi to the pathogenesis of a TRJ velocity 2.5 m/sec has not been thoroughly evaluated.3D MRA is a technology that allows detailed visualization of the pulmonary arteries. The sensitivity and the specificity of 3D MRA imaging for detecting thromboemboli in the pulmonary vasculature is 81% and 100%, respectively [8]. The sensitivity of 3D MRA is high for the segmental arteries (87%), but decreases to 55% for the subsegmental arteries [8]. Prior imaging studies of the pulmonary vasculature in individuals with SCA using conventional CT methods have demonstrated evidence of thrombi during episodes of acute chest syndrome (ACS), consistent with the process of vasoocclusion [9]. Only one study, however, has evaluated the lung vasculature in individuals with SCA and an elevated TRJ velocity. Using CT angiography to examine the pulmonary vasculature of individuals with SCA and an elevated TRJ velocity, Linguraru et al. found no thrombi or large vessel disease [10].In this study, we used 3D, contrast-enhanced MRA with a parallel imaging to evaluate the pulmonary vasculature of adults with SCA with and without an elevated...

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“…Combination of FA-MP, Ara-C and G-CSF (FLAG regimen) is active in refractory/relapsed De novo AML and poor prognosis secondary AML, with CR rates between 30-81% [239][240][241][242][243][244][245][246][247] (Table 6). Montillo et al [239] achieved above 60% CR with FLAG administered in AML patients relapsing early from chemotherapy and those relapsing from autologous stem cell transplantation (auto-SCT).…”

Section: Acute Leukemiasmentioning

confidence: 99%

“…This programme induced about 50% CR, however, with substantial myelotoxicity [242,243]. Combination of FA-MP, Ara-C and IDA (FLAI protocol) induced 71% CR in poor-risk AML patients [246].…”

Section: Acute Leukemiasmentioning

confidence: 99%

Purine Nucleoside Analogues for the Treatment of Hematological Malignancies: Pharmacology and Clinical Applications

Robak

Korycka²,

Kasznicki

et al. 2005

CCDT

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The purine nucleoside analogues (PNAs), fludarabine (FA), 2-CdA (2-chlorodeoxyadenosine, 2-CdA) and pentostatin (2'-deoxycoformycin, DCF) represent a group of cytotoxic agents with high activity in lymphoid and myeloid malignancies. PNAs share similar chemical structure and mechanism of action. Several mechanisms could be responsible for their cytotoxicity both in proliferating and quiescent cells, such as inhibition of DNA synthesis, inhibition of DNA repair and accumulation of DNA strand breaks. Induction of apoptosis through the mitochondrial pathway, direct binding to apoptosome or modulation of p53 expression all lead to apoptosis, which is the main end-point of PNA action. However, individual PNAs exhibit significant differences, especially in their interaction with enzymes involved in adenosine and deoxyadenosine metabolism. Synergistic interactions between PNAs and other cytotoxic agents (alkylating agents, anthracycline antitumor antibiotics, cytarabine, monoclonal antibodies) have been demonstrated in both preclinical and clinical studies. PNAs are highly effective in chronic lymphoid leukemias and low grade B- and T-cell non-Hodgkin's lymphomas, including Waldenström's macroglobulinemia. DCF and 2-CdA are currently the drugs of choice in hairy cell leukemia. Moreover, clinical studies have confirmed the efficacy of PNAs alone or in combination protocols in the treatment of acute myeloid leukemia and myelodysplastic syndromes. Finally, PNAs, especially FA, play an important role in non-myeloablative conditioning regimens for allogenic stem cell transplantation in high-risk patients. The toxicity profiles of PNAs are similar for all agents and consist mainly of dose-limiting myelotoxicity and prolonged immunosuppression. Three other compounds: clofarabine, nelarabine and immucillin-H are currently being evaluated clinically.

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FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies

Cited by 39 publications

References 29 publications

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G‐CSF (CLAG‐M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G‐CSF (CLAG‐M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group

Pulmonary thrombi are not detected by 3D magnetic resonance angiography in adults with sickle cell anemia and an elevated triscuspid regurgitant jet velocity

Purine Nucleoside Analogues for the Treatment of Hematological Malignancies: Pharmacology and Clinical Applications

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