Study Adds Evidence on The Link Between Leukemia Cutis and Poor Prognosis in AML

The presentation of leukemia cutis in acute myeloid leukemia (AML) may be associated with decreased overall survival and leukemia-specific survival, and these patients may require more aggressive monitoring and treatment, according to the findings of a recent study published in JAMA Dermatology.

Researchers conducted a matched-cohort, retrospective study of 1,683 patients who were diagnosed with AML between January 2005 and April 2017. The investigators analyzed data on all patients, including 78 patients with biopsy-proven leukemia cutis. The team ultimately included 62 patients with AML and leukemia cutis (mean age, 58.2 years) and matched them in a 1:3 ratio to 186 patients with AML but no leukemia cutis (mean age, 58.2 years).

The 5-year survival rate was 8.6% among the 62 patients with AML with leukemia cutis compared with 28.3% among the 186 matched patients with AML without leukemia cutis. In addition, a matched survival analysis found that patients with AML and leukemia cutis had a hazard ratio (HR) of 2.06 (95% CI, 1.26–3.38; P = .004) for leukemia-specific death compared with those without leukemia cutis; for all-cause death, the HR was 1.66 (95% CI, 1.06–2.60; P = .03). 

“There was always a belief that the presence of leukemia cutis was a poor prognostic sign, but some more recent studies were more equivocal on this. I was not surprised by the results of our study given my clinical experience caring for these patients over the last decade,” said corresponding author Milan J. Anadkat, MD, an associate professor of dermatology at Washington University School of Medicine in St. Louis, Missouri.

Anadkat reflected on the implications of these findings in an interview with Cancer Network. “I have no doubts that oncologists caring for these patients share a similar clinical impression regarding the prognosis of patients with leukemia cutis. The major take-home message is to emphasize that these leukemia subsets behave differently, and that current treatment options fall short for affected patients. Much progress has been made, but there remains work to be done,” he said.

The study indicated no differences in the odds of having secondary leukemia, NPM1 mutation, FLT3 internal tandem duplication, MLL gene rearrangement, inversion of chromosome 16, or translocation involving chromosome 8 when they compared the two groups. However, the patients with AML and leukemia cutis had higher odds of having other extramedullary organ involvement (odds ratio [OR], 3.48) and an additional chromosome 8 (OR, 2.13).

“The predilection of patients with AML and LC [leukemia cutis] to have additional sites of extramedullary involvement may reflect distinctive biological characteristics of these leukemic cells,” wrote the authors. “Further investigations are needed to understand the biological mechanisms behind leukemic infiltration of the skin and its association with patient survival, as well as to determine the most salient treatment strategies for these cases.”

Henry Fung, MD, FACP, FRCPE, vice chair of the Department of Hematology/Oncology at Fox Chase Cancer Center, said this study raises interesting questions. While it is limited by its retrospective nature and is based on only a single-institution experience, the findings may be an important first step in better understanding how areas of the skin may function as sanctuaries for leukemic cells, he said.

“This is an interesting retrospective study from a single institution with a large cohort with interesting observation,” Fung told Cancer Network. “Identifying a cohort of patients who may benefit from more intensive treatment is clinically relevant. However, having more intensive therapy may not necessarily improve treatment outcomes,” he cautioned.