Hospitals Lack Medication Needed for Form of AML, Study Finds

Although acute promyelocytic leukemia is highly treatable in early stages, the medication needed stop hematologic emergencies, all-trans retinoic acid, is often not available, a new study says.

A recent study shows that fewer than one-third of US hospitals had immediate supply of a blood cancer medication called all-trans retinoic acid (ATRA), which is used early in the treatment of acute promyelocytic leukemia (APL), a form of acute myeloid leukemia (AML).

Previous data show that APL comprises 7.4% of all patients diagnosed with AML, with an incidence rate of 2.7%. Although APL 5-year survival is higher than in other AML subtypes, the 30-day mortality for APL is significant, ranging from 15% to 25%.

Possible reasons for these early APL deaths include disease-related complications such as disseminated intravascular coagulopathy (DIC) bleeding, intracranial hemorrhage, treatment-related complications, and a lack of immediate, emergency treatment with ATRA.

Immediate administration of ATRA is recommended by the NCCN Clinical Practice Guidelines in Oncology for AML, along with other international evidence-based guidelines, for patients even suspected of having APL while waiting for genetic confirmation of the diagnosis.

For the study, researchers from a center specializing in blood cancers surveyed inpatient hospital pharmacists at hospitals with 100 beds or more in Washington, Arizona, Missouri, Georgia, Massachusetts, and Michigan, representing 6 regions of the United States. Pharmacists were asked if the hospital treats acute leukemia or does it refer to other hospitals; if the hospital pharmacy stocks oral ATRA, 10 mg tablets, on the formulary or immediately available in stock as a nonformulary request, and if not, why.

Out of 120 randomly selected hospitals, about 31% of hospitals, and 14% of hospitals that refer patients with leukemia elsewhere, had ATRA immediately available.

There were no identifiable differences in ATRA availability based on hospital size or academic versus nonacademic status of the hospital (53% vs 35%; P = .08). In hospitals that referred their patients with leukemia to other facilities, (49/118; 41.5%), only 14% (n = 7) had ATRA on their formulary or available in stock as a nonformulary request that could act as a bridge before patient transfer.

There was a significant difference in hospitals that had ATRA available based on whether they were a leukemia treatment center versus a referring center (40/69 [58%] vs 7/49 [14%], respectively; P = .000002).

However, 42% of the hospitals that confirmed they do treat patients with acute leukemia did not have ATRA in stock.

The main reasons for lack of availability of ATRA were related to the rarity of APL, or the drug had not recently been requested; the inpatient pharmacist was not familiar with the drug; or the facility relied on associated hospitals or cancer centers to provide the drug.

In addition, the authors noted another possible reason, in that the “current FDA approved indications run counter to the NCCN Guidelines, in which ATRA is a part of all frontline therapeutic recommendations for low-/intermediate-risk and high-risk disease.” Another possible reason might be that the rare incidence of APL combined with the cost to stock ATRA (average wholesale price of $2988.16 for 100 tablets of 10 mg each) may lead to a situation where a facility believes there is no reason to keeping it in stock.

“The loss of a patient with a highly curable leukemia due to the lack of access to a pill for formulary reasons would be devastating,” Dale Bixby, MD, PhD, Michigan Medicine and University of Michigan Medical School, a coauthor of the study, said in a statement. “We hope our study will lead to more widespread knowledge of the lack of availability of ATRA in hospital systems within the U.S. and spur a call to action from pharmacists and hematologists to ensure it is readily available at their institution.”

The findings were reported in the JNCCN—Journal of the National Comprehensive Cancer Network.


Geer MJ, Foucar CE, Devata S, et al. Clinical availability of ATRA for patients with suspected acute promyelocytic leukemia: Why guidelines may not be followed. Published online Augist 17, 2021. doi:10.6004/jnccn.2021.7013