Extramedullary Disease in Adult Acute Myeloid Leukemia Is Common but Lacks Independent Significance: Analysis of Patients in ECOG-ACRIN Cancer Research Group Trials, 1980-2008

Abstract

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. MethodsPatients 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. ResultsOf 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. ConclusionThis 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.

Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1

“…The The prognosis of AML with concomitant extramedullary disease remains a topic of debate, with some studies reporting an unfavorable OS between 20%-30% at 5 years, 19 and others reporting 11 The rare incidence of EMD is responsible for the limited experience in treatment of this group and unavailability of controlled prospective studies, while the incorporation of allo-HCT to treatment algorithms seems to positively impact outcomes of patients. Three retrospective studies that assessed the outcomes of patients with EMD who underwent allo-HCT reported 5-year OS rates from 36%-47%.…”

“…This subgroup of AML patients has been proposed by some authors to be considered high‐risk, with lower overall survival (OS), disease‐free survival (DFS) and complete remission (CR) rates, and higher relapse rates (RR) . Other studies report that EMD is not an independent factor associated with increased risk . The optimal choice of consolidation strategy after induction chemotherapy in patients with EMD remains unclear, as data supporting the role of allogeneic‐hematopoietic cell transplant (allo‐HCT) as a valid therapeutic option in this scenario is scarce .…”

“…9,10 Other studies report that EMD is not an independent factor associated with increased risk. 11 The optimal choice of consolidation strategy after induction chemotherapy in patients with EMD remains unclear, as data supporting the role of allogeneic-hematopoietic cell transplant (allo-HCT) as a valid therapeutic option in this scenario is scarce. 4,12,13 Recently, a retrospective multicenter study by the Center for International Blood and Marrow Transplant Research (CIBMTR) reported that patients with EMD achieved OS and DFS rates comparable to those without extramedullary involvement.…”

Clinicopathological characteristics of de novo and secondary myeloid sarcoma: A monocentric retrospective study

“…The overall incidence of MS is not clearly established, but varies among studies, ranging from 2.5% to 30% of all AML cases. 4,5,7,8 The clinical presentation of MS is highly variable and mainly related to the affected organs/sites. Non-specific symptoms include anemia, fatigue, vertigo, anorexia, weight loss, fever, and swollen lymph nodes.…”

“…18 F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) with or without computed tomography is a powerful tool not only to evaluate disease stage and activity but also to monitor treatment response. 7,8,11 We retrospectively analyzed clinicopathological data from 72 patients with MS diagnosed in the University Hospitals of Leuven.…”