Extramedullary disease is common in newly diagnosed acute myeloid leukemia, and frequently occurs in at least two sites, but is not an independent prognostic factor for overall survival, according to an analysis of 11 clinical trials.
“Importantly, the presence of extramedullary disease should not affect the choice of post-remission therapy,” concluded Dr. Chezi Ganzel of Shaare Zedek Medical Center, Jerusalem, Israel, together with his associates on behalf of the ECOG-ACRIN Cancer Research Group.
Extramedullary disease was found in anywhere from 2% to 30% of AML patients in past studies, and its prognostic impact was “unfavorable in some reports, but not in others,” the investigators noted. To help clarify the issue, they studied patients aged 15 years and up with newly diagnosed AML from 11 clinical trials conducted between 1980 and 2008. The initial study population included 3,522 patients, of which 282 were excluded for having promyelocytic leukemia (168 patients), leukemia that was not AML (29 patieints), no baseline assessment of extramedullary disease (41 patients), no survival data (20 patients), or no eligibility for retrospective central review (24 patients). That left 3,240 patients, of whom 769 (24%) had extramedullary disease. The most commonly involved sites included the lymph nodes (about 12% of patients), spleen (7%), liver (5%), skin (5%), and gingiva (4%). Only 1% of patients had detectable central nervous system involvement. Most (65%) of patients had one site of extramedullary disease, while 21% had two sites, and the rest had more extensive involvement (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.1305).
Rates of complete remission were 59.7% overall, 59% among patients with extramedullary disease, and 60% among patients without extramedullary disease, the investigators said. Just as the presence of extramedullary disease did not significantly affect the likelihood of complete remission, nor did any specific site of extramedullary disease, although there was a non-significant trend toward lower rates of complete remission among patients with splenic or gingival involvement.
The median overall survival for the cohort was 1 year. Univariate analyses linked the presence of any extramedullary disease (P = .005) and involvement of the skin (P = .002), spleen (P less than .001), and liver (P less than .001) with shorter overall survival. However, none of these relationships held up in a multivariable analysis that accounted for other significant prognostic factors, including earlier year of registration, older age, high white blood cell count, low platelet count, poor performance status, high cytogenetic risk status, and not achieving a complete remission, said the researchers.“It is possible that individual sites of extramedullary disease are, in fact, associated with poorer prognosis [but that] these patients also have other unfavorable prognostic factors, such as high white blood cell count and unfavorable cytogenetics,” the researchers commented.
Based on this large study, treatment decisions “should be made on the basis of recognized AML prognostic factors, irrespective of the presence of extramedullary disease,” they concluded.
The National Institutes of Health supported the work. Dr. Ganzel had no disclosures.