Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin

Serna, Javier de la; Montesinos, Pau; Vellenga, Edo; Rayón, Chelo; Parody, Ricardo; León, Ángel; Esteve, Jordi; Bergua, Juan; Milone, Gustavo; Debén, Guillermo; Rivas, Concha; González, Marcos; Tormo, Mar; Dı́az-Mediavilla, Joaquı́n; González, José D.; Negri, Silvia; Amutio, Elena; Brunet, Salut; Löwenberg, Bob; Sanz, Miguel Á.

doi:10.1182/blood-2007-07-100669

Cited by 302 publications

(260 citation statements)

References 25 publications

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“…2,[5][6][7][8]11 Patients with WBC counts X10 Â 10 9 /l had a higher risk of death due to fatal bleeding, as to be expected. 5,[30][31][32] The APL differentiation syndrome was diagnosed in 21.1% of our patients, which is in the range of other reports. [33][34][35][36] Possibly, the timing of ATRA and chemotherapy has contributed to the relatively high rate, as 60% of our patients received pretreatment with ATRA over a period of 7 days on average before the chemotherapy was started, as similarly observed by others.…”

Section: Discussionsupporting

confidence: 79%

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

et al. 2009

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The objective of this study for newly diagnosed acute promyelocytic Leukemia (APL) was to evaluate the efficacy of an intensified double induction chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA) followed by consolidation and 3 years maintenance therapy. In contrast to APL studies stratifying therapy according to pretreatment white blood cell (WBC) count o and X10 Â 10 9 /l (low/intermediate and high risk according to the Sanz score), our patients received uniform therapy. From 1994 to 2005, 142 patients (age, 16-60 years) were enrolled. In the low/intermediate (n ¼ 105) vs high (n ¼ 37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of induction death were 4.8 vs 16.2% (P ¼ 0.05) and of molecular remission were 87.5 vs 91.3% (P ¼ 1). Long-term overall survival was 84.4 vs 73.0% (P ¼ 0.12), event free survival was 78.3 vs 67.3% (P ¼ 0.11), relapse free survival was 82.1 vs 80.0% (P ¼ 0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P ¼ 0.46). No relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy including HD ara-C followed by prolonged maintenance therapy reduced the relapse risk in high risk patients. Pretreatment WBC count X10 Â 10 9 /l count was no relevant prognostic factor for relapse.

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Section: Discussionsupporting

confidence: 79%

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

et al. 2009

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“…Interestingly, Lam et al (17) demonstrated that this drug induces stiffening of acute lymphatic leukemia cells. Although dexamethasone is effective in APL patients there is still a substantial morbidity and mortality by RAS, and additional approaches to attenuate motility of differentiating cells are needed (41). A further increase of cell stiffening could be one such approach, which might be achieved by enhancing polymerization or cross-linking of actin filaments.…”

Section: Discussionmentioning

confidence: 99%

The regulatory role of cell mechanics for migration of differentiating myeloid cells

Lautenschläger

Paschke²,

Schinkinger³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

214

207

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Migration of cells is important for tissue maintenance, immune response, and often altered in disease. While biochemical aspects, including cell adhesion, have been studied in detail, much less is known about the role of the mechanical properties of cells. Previous measurement methods rely on contact with artificial surfaces, which can convolute the results. Here, we used a non-contact, microfluidic optical stretcher to study cell mechanics, isolated from other parameters, in the context of tissue infiltration by acute promyelocytic leukemia (APL) cells, which occurs during differentiation therapy with retinoic acid. Compliance measurements of APL cells reveal a significant softening during differentiation, with the mechanical properties of differentiated cells resembling those of normal neutrophils. To interfere with the migratory ability acquired with the softening, differentiated APL cells were exposed to paclitaxel, which stabilizes microtubules. This treatment does not alter compliance but reduces cell relaxation after cessation of mechanical stress six-fold, congruent with a significant reduction of motility. Our observations imply that the dynamical remodeling of cell shape required for tissue infiltration can be frustrated by stiffening the microtubular system. This link between the cytokeleton, cell mechanics, and motility suggests treatment options for pathologies relying on migration of cells, notably cancer metastasis.acute promyelocytic leukemia ͉ cytoskeleton ͉ microtubules ͉ optical stretcher ͉ paclitaxel

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“…Although severe bleedings can be significantly controlled with the use of ATRA, we still encounter a small number of patients being on the verge of death when they come to seek treatment, with chief complaints being serious bleedings. 43 It must be emphasized that every positive effort should be made, both in detection and in treatment. The determination of blood count, fibrinogen level, prothrombin time and partial thromboplastin time should be performed at least twice a day.…”

Section: Initial Approach For Suspected Aplmentioning

confidence: 99%

How to manage acute promyelocytic leukemia

et al. 2012

Leukemia

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Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin

Cited by 302 publications

References 25 publications

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

The regulatory role of cell mechanics for migration of differentiating myeloid cells

How to manage acute promyelocytic leukemia

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