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JCO Early Release, published online ahead of print Oct 5 2009
Received November 5, 2008 Risk of Relapse of Childhood Acute Lymphoblastic Leukemia Is Predicted By Flow Cytometric Measurement of Residual Disease on Day 15 Bone Marrow
From the Laboratorio di Oncoematologia Pediatrica, Department of Pediatrics, University, Padova; Medical Statistics Unit and Centro M. Tettamanti, Clinica Pediatrica, University of Milano-Bicocca, Ospedale San Gerardo, Monza; Department of Pediatric Hematology Oncology, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy; Children's Cancer Research Institute and St Anna Children's Hospital, Vienna, Austria; and Hematology, Oncology and Tumor Immunology, Robert-Roessle-Clinic at the HELIOS Klinikum Berlin, Charité Medical School, Berlin, Germany. * To whom correspondence should be addressed. E-mail: m.arico{at}meyer.it
Purpose: Speed of blast clearance is an indicator of outcome in childhood acute lymphoblastic leukemia (ALL). Availability of measurement of minimal residual disease (MRD) at an early time point with a reduced-cost method is of clinical relevance. In the AIEOP-BFM-ALL (Associazione Italiana Ematologia Oncologia Pediatrica and Berlin-Frankfurt-Münster Study Group) 2000 trial, patients were stratified by levels of polymerase chain reaction (PCR) MRD at day +33 and +78. AIEOP studied the prognostic impact of MRD measured by flow cytometry (FCM) at day 15 of induction therapy. Patients and Methods: Bone marrow samples from 830 Italian patients were collected on day 15, after 14 days of steroids, and one dose of intrathecal methotrexate, vincristine, daunorubicine, and asparaginase. Cells were analyzed by four-color FCM for detection of leukemia-associated immunophenotypes. Results: Three patient risk groups were identified by FCM: standard (< 0.1% blast cells; 42% of the total), intermediate (0.1 to < 10%; 47%), and high ( Conclusion: Measurement of FCM MRD in day 15 bone marrow was the most powerful early predictor of relapse, applicable to virtually all patients; it may complement PCR MRD–based stratification including later time points, thus allowing additional treatment tailoring.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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10%; 11%). Their 5-year cumulative incidences of relapse were 7.5% (SE, 1.5), 17.5% (SE, 2.1), and 47.2% (SE, 5.9), respectively. In multivariate analysis, FCM was the most important prognostic factor among those available by day 15, with two-fold and five-fold increase in the risk of relapse compared with patients with less than 0.1%. PCR MRD, when added to the model, had significant prognostic impact; yet high levels of FCM MRD retained an independent ability to detect a significantly higher risk of relapse.
