Complex Karyotype but Not Blast Percentage Is Associated with Poor Survival in Acute Myeloid Leukemia and Myelodysplastic Syndrome with Inv(3)(q21q26.2)/t(3;3)(q21;q26.2); a Bone Marrow Pathology Group Study
Heesun J Rogers, James W Vardiman, John Anastasi, Gordana Raca, Natasha M Savage, Athena M Cherry, Daniel Arber, Erika Moore, Jennifer JD Morrissette, Adam Bagg, Yen-Chun Liu, Susan Mathew, Attilio Orazi, Pei Lin, Sa A Wang, Carlos E Bueso-Ramos, Kathryn Foucar, Robert P Hasserjian, Eric D Hsi. Cleveland Clinic, Cleveland, OH; University of Chicago, Chicago, IL; Stanford University, Stanford, CA; University of Pennsylvania, Philadelphia, PA; Weill Medical College of Cornell University, New York, NY; MD Anderson Cancer Center, Houston, TX; University of New Mexico, Albuquerque, NM; Massachusetts General Hospital, Boston, MA
Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) [inv3/t3] have poor prognosis. The revised International Prognostic Scoring System (IPSS-R) includes inv3/t3 MDS in a poor risk karyotype group. However, inv3/t3 MDS is not among the genetic abnormalities for diagnosis of AML irrespective of blast percentage (%) in the 2008 WHO classification.
Design: This multicenter study aims to evaluate clinicopathologic features and outcome in inv3/t3 AML/MDS patients and to apply the IPSS-R to inv3/t3 MDS patients.
Results: 103 inv3/t3 patients (median 57.1 years) had median BM blast 4% in MDS (N=40) and 52% in AML (N=63) (p<.001). 91% of patients showed small uni/bilobated megakaryocytes. Dysgranulopoiesis, dyserythropoiesis and multilineage dysplasia were common (49%, 60%, 62% respectively). -7/del7q (37%) was a common cytogenetic abnormality. 17% of patients had prior therapy for solid tumor/lymphoma. 57% of inv3/t3 MDS evolved to AML. There was no difference in overall survival (OS) between inv3/t3 MDS and AML (12.9 vs 7.9 mo, p=.15). 83% of patients expired (median follow up of 7.9 mo). Patients with structurally complex or monosomal karyotype had shorter OS compared to patients with non-complex or non-monosomal karyotype (4.5 vs 11 mo, p<.001; 6 vs 11 mo, p=.002, respectively). Complex karyotype retained independent prognostic significance (p<.05) in multivariate analysis. The IPSS-R scores in inv3/t3 MDS were higher relative to IPSS score (p<.001). However, 72.5% and 77.5% of inv3/t3 MDS patients still had shorter OS than expected OS by IPSS-R and IPSS scores.
Conclusions: The IPSS-R better reflects the OS of inv3/t3 than IPSS but may not fully reflect the generally dismal prognosis. Patients with inv3/t3 MDS and AML follow a similarly aggressive clinical course, supporting consideration of inv3/t3 MDS as an AML with recurrent genetic abnormalities irrespective of blast %.
Tuesday, March 5, 2013 8:30 AM
Proffered Papers: Section C, Tuesday Morning