Atypical chronic myeloid leukemia (aCML) presents multiple challenges for researchers and practitioners. Rare, aggressive, and sharing overlapping features with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), aCML has no established standard of care and a staggeringly poor prognosis: median survival less is than 2 years.

“This is a very rare disease with a dismal prognosis and, so far, there is no targeted therapy, and no mutation or gene aberration that has been identified as responsible for the disease,” said Dr Francisco Onida of the department of oncology and hemato-oncology at the University of Milan in Italy. “So we don’t have any drug that we can use with these patients.”

That leaves oncologists and patients with limited treatment options.

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Resembling CML in clinical and laboratory features, aCML lacks the Philadelphia chromosome and the BCR-ABL1 fusion gene. CML accounts for some 15% to 25% of adult leukemias, with about 8220 new cases occurring in the United States in 2016.1 Atypical CML occurs in only an estimated 1 to 2 percent of those. It is a uniquely challenging subset. While the introduction of imatinib and related targeted therapies aimed directly at blocking the BCR-ABL mutation more than doubled the 5-year survival rate of patients with CML to 65%, no similar drugs have proven effective against aCML.

Neither have hypomethylating agents, although some are calling for further examination of these and other therapies because of their effectiveness in treating MDS and MPN disorders.

“Of particular interest are the effects of biologic therapies in aCML and CNL [chronic neutrophilic leukemia], for example, interferon-alpha, hypomethylating agents, and TNF-alpha inhibitors,” Drs Kim-Hien T. Dao and Jeffrey W. Tyner of the Knight Cancer Institute at Oregon Health & Science University in Portland wrote in a 2015 article.2

Interferon-alpha, they noted, “can induce hematologic and molecular remissions in Philadelphia-negative MPN patients.”

Similarly, the authors continued, the success of the hypomethylating agent azacitidine in improving overall survival of high-risk patients with MDS makes it worth studying in aCML cases.

“Testing the safety and efficacy of azacitidine is certainly a concept to consider especially in aCML where there are overlapping morphologic, molecular, and cytogenetic features with MDS.”

To date, though, the only known curative therapy for aCML involves stem cell transplantation. But that carries high risks of toxicity and morbidity, especially in older patients. It also involves a high rate of relapse.

Yet in a retrospective analysis looking at patient records between 1997 and 2006, Dr Onida and a group of co-authors found that allogeneic stem cell transplantation showed noteworthy promise in patients 45 years and younger.3

Given the rarity of the disease, the analysis published in March gleaned a small cohort of only 42 patients from the decade of records. In those, however, the authors found that “following allo-HSCT [allogeneic hematopoietic stem cell transplant], 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality was 24%, while relapse occurred in 40%.”

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The findings are encouraging, Dr Onida said, given the typically poor survival for patients with aCML treated with other therapies or given only supportive care.

He also pointed out that the most recent records included in the analysis are now more than 10 years old. Advances in transplantation conditioning regimens since then have improved survival rates significantly, he noted.