I Got Married and Then I Got Back on a Flight and I'm Like Hey, What Did You Do This Weekend?

Emergencies happen in hematology and oncology. This is a fact. But how do we manage these emergencies? Look no further.

In this episode, we’ll talk about one of the key hematologic malignancies that you’ll encounter as a fellow, one that requires immediate action to reduce mortality: acute promyelocytic leukemia (APL or APML)

- Acute Promyelocytic leukemia (APL or APML):

**Stay tuned for our upcoming “part two” and “chemotherapy basics” episodes for more information on non-acute management of this disease

**APL is a true hematologic emergency! Although this is a very curable form of leukemia, it is associated with high rates of severe DIC and high mortality in the period immediately following diagnosis

***Untreated, can see pulmonary or cerebrovascular hemorrhage in up to 40% of patients

***10-20% incidence of hemorrhage-related mortality in the initial period

***Statistically significant increase in mortality at 30 days with just a 12-hour delay in initial hematologist consultation

- Disease basics:

** Rare subtype of AML( <10% of cases)

** Driven by translocations involving the retinoic acid receptor alpha (RARA) on chromosome 17, classically with the promelocytic leukemia gene (PML) on chromosome 15 [i.e. t(15;17)]

***Other non-classical translocations exist, but nearly all involve RARA

**Because of this driver mutation, treatment with a specific isoform of vitamin A: all-trans retinoic acid (ATRA) forces promyelocytes to differentiate and ultimately apoptose 

- Initial work up:

**Standard CBC with differential, CMP

** Review smear for characteristic features:

** Large nuclei and scant cytoplasm

** “Folded” appearance to nuclei (like a peach emoji 🍑)

** Auer rods (which tells you blasts are myeloid lineage)

** Heavily granulated cytoplasm (hypergranular form - most common)

***Also a “hypogranular variant,” so like always, make sure to discuss any findings with your friendly neighborhood hematopathologist

**Stat DIC labs:

**PT/aPTT

**Fibrinogen

**Stat PML-RARA FISH (see next section) to look for classic driver mutation and clinch diagnosis

** “Tumor lysis syndrome (TLS) labs”

***LDH

*** Uric acid

**Peripheral flow cytometry

***CD33+, CD 117+

***CD34-, HLA-DR-, CD11a/b/c-

*** Increased side scatter (esp in hypergranular type)

- Acute Management

** Start ATRA: immediate treatment is so important in this disease, and side effect profile is minimal enough that empiric treatment when disease is on the differential is standard of care

**Correct coagulopathies as you detect them 

***Keep fibrinogen > 110 mg/dL

*** Keep INR < 2.0

*** Keep plt > 30k/uL

References:

Gulam Abbas Manji, Samira Khan Manji, Sheetal Karne, and Jeff Chao “Time to ATRA in suspected newly diagnosed acute promyelocytic leukemia and association with early death rate at a non-cancer center institution: Are we meeting the target?” Journal of Clinical Oncology 2012 30:15_suppl, 6615-6615 - impact of treatment delay on 30-day mortality

Eytan M. Stein, Neerav Shukla, Jessica K. Altman “Chapter 20: Acute Myeloid Leukemia” section on acute promyelocytic leukemia ASH SAP 7th Ed pp588-590. DOI: 10.1182/ashsap7.chapter20

Warrell RP Jr, de Thé H, Wang ZY, Degos L. Acute promyelocytic leukemia. N Engl J Med. 1993 Jul 15;329(3):177-89. doi: 10.1056/NEJM199307153290307. PMID: 8515790. - Great review of the basics in NEJM from the early 2000s

Sanz MA, Fenaux P, Tallman MS, Estey EH, Löwenberg B, Naoe T, Lengfelder E, Döhner H, Burnett AK, Chen SJ, Mathews V, Iland H, Rego E, Kantarjian H, Adès L, Avvisati G, Montesinos P, Platzbecker U, Ravandi F, Russell NH, Lo-Coco F. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019 Apr 11;133(15):1630-1643. doi: 10.1182/blood-2019-01-894980. Epub 2019 Feb 25. PMID: 30803991. - Updated treatment guidelines (more on this in “Part 2” to come)

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