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 (ATRA) and arsenic trioxide (ATO) are classic examples of differentiating agents for treatment of acute promyelocytic leukemia (APL); newer therapies functioning through differentiation include isocitrate dehydrogenase (IDH) 1 and 2 inhibitors, FMS-like tyrosine kinase 3 (FLT3) 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 (SIRS)-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 non-specific signs and symptoms which 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.
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Review Article|
July 8, 2024
How I Treat: Differentiation Therapy in Acute Myeloid Leukemia
Ghayas C. Issa,
Ghayas C. Issa
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
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Eytan M. Stein,
Eytan M. Stein
Memorial Sloan Kettering Cancer Center, New York, New York, United States
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Courtney D. D DiNardo
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
* Corresponding Author; email: [email protected]
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Blood blood.2024024008.
Article history
Submitted:
May 17, 2024
Revision Received:
June 10, 2024
Accepted:
June 29, 2024
Citation
Ghayas C. Issa, Eytan M. Stein, Courtney D. D DiNardo; How I Treat: Differentiation Therapy in Acute Myeloid Leukemia. Blood 2024; blood.2024024008. doi: https://doi.org/10.1182/blood.2024024008
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