De Novo Acute Myeloid Leukemia (AML) with inv(3) or t(3;3): A Clinicopathologic Study of 30 Cases
J Sun, S Konoplev, S Chen, W Cui, LJ Medeiros, P Lin. M.D. Anderson Cancer Center, Houston, TX
Background: AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) is a distinct type of AML only recently recognized in the 2008 World Health Organization classification. Very few clinicopathologic studies on de novo AML with inv(3)/t(3;3) were reported in the literature.
Design: We identified 30 cases of de novo AML with inv(3)/t(3;3) confirmed by conventional cytogenetic analysis. Patients with a history of myelodysplastic syndrome, myeloproliferative neoplasm or therapy-related AML were excluded. Clinicopathological features were correlated with overall survival (OS).
Results: 29 of 30 (97%) patients were adults, 28 to 77 years of age (median, 53 years); 10 (33%) patients were under 40 years. Platelet counts were highly variable (range, 21-597 k/μL; median, 128 k/μL), and 2 patients (7%) had thrombocytosis (>450 k/mL) at presentation. Morphologically, acute myelomonocytic leukemia was most prevalent (11/30, 37%); followed by AML with minimal differentiation or AML with maturation (5/30, 17% each), AML without maturation (3/30, 10%), and acute megakaryoblastic leukemia (2/30, 7%). Morphological evidence of dysplasia was observed in at least one lineage in 23/25 (92%) cases in which maturing elements could be assessed. 5 (17%) patients had inv(3)/t(3;3) as the sole abnormality, whereas 10 (33%) patients had a complex karyotype (≥3 additional abnormalities). The most frequent additional aberration was -7, in 12/30(40%) patients, detected in 1 case as part of a subclone. FLT3/ITD mutation was identified in 2/23 (9%) cases. The 1-year, 3-year and 5-year OS rates were 33% (CI: 24-42%), 10% (CI: 5-15%) and 5% (CI: 1-9%), respectively. Age, hemoglobin, white blood cell, platelet or bone marrow blast levels at presentation did not correlate with survival. Patients with -7 in addition to inv(3)/t(3;3) did not have a worse survival than those with isolated inv(3)/t(3;3) (p=0.19). There was no survival difference between patients with or without a complex karyotype. Patients treated with allogeneic stem cell transplantation (n=11) had a significantly better survival than those treated with chemotherapy alone (n=17) (16.1 versus 8.0 months, p=0.007).
Conclusions: AML with inv(3)/t(3;3) is an aggressive type of AML that afflicts adult patients of all ages. FLT3/ITD mutation is rare. Monosomy 7 identified as part of a subclone suggests that -7 may not be a primary event. Patients with inv(3)/t(3;3) have a poor survival regardless karyotypic complexity. Allogeneic stem cell transplantation is associated with a better outcome.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 186, Wednesday Afternoon