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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-08-2613.

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2002-08-2613v1
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Submitted August 30, 2002
Accepted January 21, 2003

Minimal residual disease (MRD) in adolescent (> 14 years) and adult acute lymphoblastic leukaemias (ALL): Early immunophenotypical evaluation has high clinical value

Maria B Vidriales*, Jose J Perez, Consuelo Lopez-Berges, Norma Gutierrez, Juana Ciudad, Paulo Lucio, Lourdes Vazquez, Ramon Garcia-Sanz, Consuelo del Canizo, Javier Fernandez-Calvo, Fernando Ramos, Maria J Rodriguez, Maria J Calmuntia, Ana Porwith, Alberto Orfao, and Jesus F San-Miguel

Hematology, University Hospital, Salamanca, Spain
Cytometry, University of Salamanca, Salamanca, Spain
Hematology, Portuguese Institute of Oncology, Lisbon, Portugal; European BIOMED-1 Concerted Action (BMH-CMT 94-1675)
Hematology, University Hospital, Valladolid, Spain
Hematology, Complejo Hospitalario, Leon, Spain
Hematology, General Hospital, Avila, Spain
Hematology, General Hospital, Segovia, Spain
Pathology, Karolinska Institute, Stochkolm, Sweden; European BIOMED-1 Concerted Action (BMH-CMT 94-1675)
Cytometry, University of Salamanca, Salamanca, Spain; Centro de Investigacion del Cancer, Salamanca, Spain; European BIOMED-1 Concerted Action (BMH-CMT 94-1675)
Hematology, University Hospital, Salamanca, Spain; Centro de Investigacion del Cancer, Salamanca, Spain; European BIOMED-1 Concerted Action (BMH-CMT 94-1675)

* Corresponding author; email: mvidrialesv{at}aehh.org.

Investigation of minimal residual disease (MRD) in acute leukemias is proving to be increasingly valuable for disease monitoring. In ALL, most MRD studies have focused on children, and information on adult ALL is scanty, almost exclusively restricted to PCR studies. Early response to therapy is one of the most important prognostic factors in acute leukaemia, which prompted us to investigate if early immunophenotypical assessment of MRD could be useful for predicting relapse in ALL. Therefore, we have analysed the level of MRD during the initial phase of treatment, by multiparameter flow cytometry, in a series of 102 adolescent (> 14 years) and adult ALL patients. Immunophenotypic evaluation of the BM at day +35, showed that patients with <0.05% MRD levels had a significantly longer RFS than patients with higher MRD levels, and this prognostic influence was retained when only patients in morphological complete remission were considered (median RFS: 42 vs 16 months) (p=0.001). Moreover, immunophenotyping helped to identify a small subset of patients (n=12) with negative or low MRD level (<0.03% LAP+ cells) by day +14, with an excellent prognosis (projected RFS of 90% at 5 years). Among late mCR achievers (after day +35), none of cases with >0.1 MRD level was relapse-free after two years. Multivariate analysis showed that immunological evaluation of MRD at day +35 was the most relevant independent prognostic parameter for adult ALL patients, and together with age and WBC at diagnosis, and Ph chromosome represented the most informative combination of variables for predicting relapse-free survival.


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