How I treat acute myeloid leukemia with differentiation therapy Review


Authors: Issa, G. C.; Stein, E. M.; DiNardo, C. D.
Review Title: How I treat acute myeloid leukemia with differentiation therapy
Abstract: An increasing number of acute myeloid leukemia (AML) therapeutics have been developed, not as cytotoxic therapies but rather as targeted agents able to restore the aberrant and leukemogenic “block” in normal differentiation. All-trans retinoic acid and arsenic trioxide are classic examples of differentiating agents for treatment of acute promyelocytic leukemia (APL); newer therapies functioning through differentiation include isocitrate dehydrogenase 1 and 2 inhibitors, FMS-like tyrosine kinase 3 inhibitors, and menin inhibitors. The terminal differentiation of leukemic blasts via differentiating-agent therapy can lead to a constellation of signs and symptoms, originally referred to as “retinoic acid syndrome” and now termed “differentiation syndrome” (DS), characterized predominantly by systemic inflammatory response system–like features of dyspnea, pulmonary infiltrates, pleural and pericardial effusions, unexplained fevers, hypotension, edema, and renal insufficiency. DS in patients with newly diagnosed APL is generally straightforward to identify; however, DS in patients with multiply relapsed AML can be more challenging to diagnose, due to nonspecific signs and symptoms that can be mistakenly attributed to infectious etiologies or the underlying refractory leukemia itself. Prompt consideration of DS, rapid initiation of systemic corticosteroids, and early cytoreduction in the setting of concomitant hyperleukocytosis are essential for optimal management. © 2025 American Society of Hematology
Keywords: adult; controlled study; review; kidney failure; cell differentiation; dyspnea; fever; arsenic trioxide; hypotension; diagnosis; promyelocytic leukemia; corticosteroid; pericardial effusion; retinoic acid; lung infiltrate; isocitrate dehydrogenase 1; cd135 antigen; acute myeloid leukemia; differentiation therapy; isocitrate dehydrogenase 2; human; male; female; differentiation syndrome
Journal Title: Blood
Volume: 145
Issue: 12
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2025-03-20
Start Page: 1251
End Page: 1259
Language: English
DOI: 10.1182/blood.2024024008
PUBMED: 38976876
PROVIDER: scopus
PMCID: PMC11952016
DOI/URL:
Notes: Source: Scopus
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  1. Eytan Moshe Stein
    368 Stein