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Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet.

ABSTRACT: Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion-based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid- and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.

SUBMITTER: Sanz MA

PROVIDER: S-EPMC6509567 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet.

Sanz Miguel A MA Sanz Miguel A MA Fenaux Pierre P Tallman Martin S MS Estey Elihu H EH Löwenberg Bob B Naoe Tomoki T Lengfelder Eva E Döhner Hartmut H Burnett Alan K AK Chen Sai-Juan SJ Mathews Vikram V Iland Harry H Rego Eduardo E Kantarjian Hagop H Adès Lionel L Avvisati Giuseppe G Montesinos Pau P Platzbecker Uwe U Ravandi Farhad F Russell Nigel H NH Lo-Coco Francesco F

Blood 20190225 15

Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion-based recommendations on the management of this ...[more]

PMID: 30803991

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Project description:This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood?>?2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.

Dataset Information

Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet.

Publications

Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet.

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