Acute Promyelocytic Leukemia at Time of Relapse: Clinicopathologic Findings and Results of Ancillary Testing
ND Dimov, C Bueso-Ramos, LJ Medeiros. MD Anderson Cancer Center, Houston, TX
Background: Although the therapy for acute promyelocytic leukemia (APL) is effective, up to 40% of patients relapse. The biological characteristics of APL at time of relapse are not well described. In this study we evaluated the morphologic, immunophenotypic, molecular and cytogenetic characteristics of APL at time of relapse and compared these findings with initial diagnostic specimens before therapy.
Design: We retrospectively reviewed clinicopathologic data and the results of ancillary testing in all APL patients treated in our institution between 2001 and 2008.
Results: Clinical and/or hematologic relapse occurred in 12 of 112 (10.7%) patients. Time to relapse ranged from 6 to 49 months (mean 19 months). Two patients relapsed twice and 1 patient had three relapses. The sites of relapse were bone marrow (BM) (n=8), BM with extramedullary sites (n=3), and central nervous system (CNS) (n=1). Two patients died from intracranial bleeding and CNS relapse. While in second remission 2 patients died from meningitis and sepsis, respectively. BM blasts varied from 71 to 96% (mean 83.3%) at initial diagnosis and from 0 to 82% (mean 39.2%) at relapse. Peripheral blood blasts ranged from 1.44 to 126.1 x 109/L (mean 47.29) at initial diagnosis and from 0 to 46.78 x 109/L (mean 5.87) at relapse. Slides of the initial BM specimens were available in 8 patients; blast cell morphology was similar in 7 and changed from microgranular to typical in 1 patient. Flow cytometry immunophenotyping was performed on both the initial and relapse specimens in 6 patients: at relapse 2 cases expressed CD33 and HLA-DR, 1 case expressed CD34, 1 case showed increased CD117 intensity, and 1- decreased CD13 intensity. Cytogenetic studies, performed on both the initial and relapse specimens in 9 patients, showed 5 identical karyotypes, additional aberrations at relapse in 3 cases (including +8, t(9;11) and complex), and diploidy in 1 case. All 11 patients tested by PCR at time of relapse were positive.
Conclusions: Changes in blast cell morphology (from microgranular to typical), immunophenotype (gain or loss of antigens), and cytogenetics (diploid or complex karyotypes) can occur at time of APL relapse. Although conventional cytogenetic studies may not be adequately sensitive to detect all APL relapses, they are helpful for detecting additional aberrations that occur in a subset of patients. These findings underline the importance of a multidisciplinary approach incorporating morphological and ancillary studies for evaluating APL patients in follow up BM specimens.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 179, Wednesday Afternoon