Early death in acute promyelocytic leukemia (APL) in French centers: a multicenter study in 399 patients

Rahmé, Ramy; Thomas, Xavier; Récher, Christian; Vey, Norbert; Delaunay, Jacques; Deconinck, Eric; Hirsch, Pierre; Bron, Dominique; Jb, Micol; Stamatoullas, Aspasia; Mariette, Clara; Pautas, Cécile; Bories, Pierre; Jp, Marolleau; Hunault, Mathilde; Fégueux, Nathalie; Raffoux, Emmanuel; Dombret, Hervé; Degos, Laurent; Fenaux, Pierre; Adès, Lionel

doi:10.1038/leu.2014.240

Cited by 55 publications

(34 citation statements)

References 11 publications

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“…Conversely, during the period of accrual in the APL-2006 trial, a thorough analysis of all APLs diagnosed in the 17 largest participating centers was made. We observed that 68.7% of patients had been included in the APL trial, whereas 31.3% had not been included for a variety of reasons (mainly older age and direct admission to the hospital's intensive care unit), 17 The proportion of secondary APL was 15% in patients who were included in the APL0200 6 trial and 8.8% in those who were not included.…”

Section: Discussionmentioning

confidence: 93%

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French‐Belgian‐Swiss APL group

Braun

Cereja

Chevret

et al. 2015

Cancer

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the French-Belgian-Swiss APL Group BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL. METHODS: The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P 5.03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P <.001). Treatment of the primary tumor in the APL-2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P 5.044) and no mitoxantrone (0% vs 46.7%; P 5.016) but more frequently included anthracyclines (53.3% vs 38.3%; P 5.015). In the APL-2006 trial, patients who had secondary APL, compared with those who had de novo APL, were older (mean, 60.2 years vs 48.7 years, respectively; P <.0001) but had a similar complete response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0% vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18 months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL. Cancer 2015;121:2393-9.

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Section: Discussionmentioning

confidence: 93%

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French‐Belgian‐Swiss APL group

Braun

Cereja

Chevret

et al. 2015

Cancer

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“…53 However, the mortality during the induction period of the first 30 days, commonly referred to as early death (ED), remains high, ranging from 3 to 61% (►Table 1), with hemorrhagic complications being the major cause. 19,20,[54][55][56][57] The wide range on the incidence of ED is related to the year of survey (before or after introduction of differentiating agents), age of patients, whether or not it is a cooperative trials or populationbased study, treatment regimen, and supporting measures. 16,54 Most reports on the incidence of ED occurring prior to the ATRA/ATO era are generally higher.…”

Section: Outcomementioning

confidence: 99%

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Kwaan

Weiss

Tallman

2019

Semin Thromb Hemost

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Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.

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“…The estimate was even higher in patients $55 years of age, reaching a value of 24.2%. 16 In a French study, the risk of ED was 17% for individuals treated outside of a trial, 17 compared with 21.8% for the whole cohort in a pan-Canadian registry. 18 Because most patients receiving induction therapy for APL do so outside of the trial setting, from a general perspective, early hemorrhagic death (HD) remains a major challenge in the management of this neoplasm.…”

Section: Introductionmentioning

confidence: 99%

Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era

Mantha¹,

Goldman

Devlin

et al. 2017

Blood

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• High WBC is an independent predictor of early HD in APL.Acute promyelocytic leukemia (APL) is commonly complicated by a complex coagulopathy. Uncertainty remains as to which markers of bleeding risk are independent predictors. Drawing from 5 large clinical trials that included all-trans retinoic acid (ATRA) as part of induction, we assessed known determinants of bleeding at baseline and evaluated them as potential predictors of hemorrhagic death (HD) in the first 30 days of treatment. The studies included were ALLG APML3 (single arm of ATRA 1 idarubicin 6 prednisone), ALLG APML4 (single arm of ATRA 1 idarubicin 1 arsenic trioxide 1 prednisone), CALGB C9710 (single arm of ATRA 1 cytarabine 1 daunorubicin), Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2491 (intergroup I0129, consisting of daunorubicin 1 cytarabine vs ATRA), and SWOG S0521 (single-arm induction of ATRA 1 cytarabine 1 daunorubicin). A total of 1009 patients were included in the original trials, of which 995 had sufficient data to be included in our multivariate analysis. In this final cohort, there were 37 HD cases during the first 30 days following induction, for an estimated cumulative incidence of 3.7% (95% confidence interval [CI], 2.6% to 5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio of HD in the first 30 days was 2.17 (95% CI, 0.84-5.62) for an ECOG performance status of 3-4 vs 0-2 and 5.20 (95% CI, 2.70-10.02) for a white blood cell count of ‡20 000/mL vs <20 000/mL. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor

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Early death in acute promyelocytic leukemia (APL) in French centers: a multicenter study in 399 patients

Cited by 55 publications

References 11 publications

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French‐Belgian‐Swiss APL group

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French‐Belgian‐Swiss APL group

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era

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