Differentiation syndrome in acute promyelocytic leukaemia

Stahl, Maximilian; Tallman, Martin S.

doi:10.1111/bjh.16151

Cited by 108 publications

(120 citation statements)

References 20 publications

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“…Moreover, while the outcome of DS incidence did not change when assessing those with a low or moderate risk of bias, we expect that clinical trial reports are subject to misclassification bias, rooted in the lack of universally applied diagnostic criteria for DS and the unspecific nature of its symptoms, particularly for the non-M3 AML patients treated with IDH-inhibitors [ 7 , 104 ]. Another limitation is that we focused our review on the occurrence of DS and, therefore, did not summarize information on disease-free survival or relapse rate.…”

Section: Discussionmentioning

confidence: 99%

Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature

Gasparovic

Weiler

Higi

et al. 2020

JCM

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Differentiation syndrome (DS) is a potentially fatal adverse drug reaction caused by the so-called differentiating agents such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), used for remission induction in the treatment of the M3 subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL). However, recent DS reports in trials of isocitrate dehydrogenase (IDH)-inhibitor drugs in patients with IDH-mutated AML have raised concerns. Given the limited knowledge of the incidence of DS with differentiating agents, we conducted a systematic literature review of clinical trials with reports of DS to provide a comprehensive overview of the medications associated with DS. In particular, we focused on the incidence of DS reported among the IDH-inhibitors, compared to existing ATRA and ATO therapies. We identified 44 published articles, encompassing 39 clinical trials, including 6949 patients. Overall, the cumulative incidence of DS across all treatment regimens was 17.7%. Incidence of DS was notably lower in trials with IDH-inhibitors (10.4%) compared to other regimens, including ATRA and/or ATO (15.4–20.6%). Compared to other therapies, the median time to onset was four times longer with IDH-inhibitors (48 vs. 11 days). Treating oncologists should be mindful of this potentially fatal adverse drug reaction, as we expect the current trials represent an underestimation of the actual incidence.

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Section: Discussionmentioning

confidence: 99%

Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature

Gasparovic

Weiler

Higi

et al. 2020

JCM

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“…One key problem when studying DS pathogenesis or to identify biomarkers of this syndrome is the fact that the current diagnosis is widely supported by not well de ned clinical criteria and that the diagnostic process is challenging when the signs and symptoms attributable to DS occur in APL patients who also develop complications such as pneumonia, cardiac toxicity, renal failure, and septic shock [6]. Considering the APL-DS patients with apparently no other complications, Montesinos et al proposed criteria for APL-DS severity grading based on the presence of prede ned signs and symptoms [22] but this classi cation has not been widely adopted in practice as occurred in the current study once the number of patients enrolled in the cohort did not allow a strati ed analysis of the DSgroup.…”

Section: Discussionmentioning

confidence: 99%

“…During the APL-DS, changes in seric levels of cytokines [1], and in cellular adhesion/migration properties [2,3,4], as well as endothelial damage [5] have been reported to be related to ATRA-driven DS. Most of the cases manifest with dyspnea, pulmonary in ltrates, unexplained fever, more than 5 Kg weight gain, pleural and/or pericardial effusion, hypotension, and renal failure [4,6].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome

Almeida

Pereira-Martins

Lima

et al. 2020

Preprint

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Background Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of APL-DS. However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in APL patients during the treatment with ATRA and anthracyclines has not been previously reported. Methods In this study, we followed an APL cohort (n = 17) over seven days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 APL patients and 11 healthy adult controls by using the cytometric bead array method. Results In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment whereas their levels did not discriminate between DS and non-DS development. No significant differences were found in IL-6 levels between groups. Other cytokines tested were all undetectable in APL patients or healthy controls. Conclusions We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.

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“…Differentiation syndrome (DS) is a life-threatening adverse event that occurs in approximately 20-25% of patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA) [1,2]. During the APL-DS, changes in seric levels of cytokines [3], and in cellular adhesion/migration properties [1,4,5], as well as endothelial damage [6] have been reported to be related to ATRA-driven DS.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome

et al. 2020

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Background: Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported. Methods: In this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method. Results: In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL − 1 in D0 vs. 10.9; 0 to 26.81 pg mL − 1 in D7; p = 0.02) whereas their levels did not discriminate between DS and non-DS development during the entire induction period (all p > 0.05 in D0, D3, and D7). No significant differences were found in IL-6 levels between groups (p > 0.05 in D0-D7). Other cytokines tested were all undetectable in patients with APL or healthy controls. Conclusions: We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.

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Differentiation syndrome in acute promyelocytic leukaemia

Cited by 108 publications

References 20 publications

Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature

Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature

Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome

Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome

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