Extramedullary Disease (EMD) is a recognized manifestation of Acute Myeloid Leukemia (AML). However, reports on the incidence amongst AML patients are inconsistent and the prognostic implications of this condition are not clearly defined.
Ganzel et al. conducted a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an effort to ascertain the incidence and clinical implications of EMD. Their findings were published in The Journal of Clinical Oncology in 2016.
The key findings were:
- The overall incidence of EMD within this patient population was 23.7% (769 of 3,240 patients).
- The majority of patients with EMD (n = 502, 65.3%) had only one site of EMD.
- Patients with EMD, compared with those without EMD, were younger (median age, 45.7 v 52.9 years; P < .001) and males (57.9% v 52%; P = .006).
- Patients with EMD had a poorer performance status (PS; 76.4% with Eastern Cooperative Oncology Group PS 0-1 v 86%; P < .001) compared to those without EMD.
- In addition, patients with EMD had a higher median percentage of blasts in the bone marrow and in the peripheral blood.
- The complete remission (CR) rate for all patients was 59.7% and was similar for patients with or without EMD (59% and 60%, respectively).
- The CR rate was similar for patients with individual EMD sites except for those with splenic and gingival involvement, who had a non-significant lower CR rate compared with the whole cohort (P = .06 and .08, respectively).
- The median overall survival (OS) was 1.035 years. There were 2,625 deaths among the 3,240 patients included in the analysis.
- Patients with EMD had a shorter OS (P = .005; Fig 1A).
- Among individual EMD sites, the analysis revealed that skin (P = .002), spleen (P < .001; Fig 1B), and liver (P < .001), but not CNS (P = .34; Fig 1C), nodal involvement (P = .94), and gingival hypertrophy (P = .24), were associated with shorter OS.
EMD and Cytogenetics:
- No significant difference in OS was observed between the groups, however, this a very small sample set (Fig 1D).
Fig 1. Differences in overall survival by (A) presence of extramedullary disease, (B) presence of splenic involvement, (C) presence of CNS involvement, and (D) combination of cytogenetic risk and presence of extramedullary involvement. P values are from the log-rank test. Cyto, cytogenetic; EMD, extramedullary disease; fav, favorable; intermed, intermediate; pts, patients; unfav, unfavorable.
In conclusion, these data represent the largest sample size pertaining to EMD. The authors have demonstrated that the presence of EMD was independent of the CR rate. Nonetheless, there were shorter OS rates with patients identified as having EMD. Of clinical significance is the fact the authors state that the presence of EMD did not affect the choice of post-remission therapy.
Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD.
Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results.
Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites.
The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD (P = .005), skin involvement (P = .002), spleen (P < .001), and liver (P < .001), but not CNS (P = .34), nodal involvement (P = .94), and gingival hypertrophy (P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic.
This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.