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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4563-4569.
Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-09-3634.
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Submitted September 9, 2005
Accepted January 20, 2006
Clinical significance of minimal residual disease, as assessed by different techniques, after stem-cell transplantation for chronic lymphocytic leukemia
Carol Moreno, Neus Villamor, Dolors Colomer, Jordi Esteve, Eva Gine, Ana Muntanola, Elias Campo, Francesc Bosch, and Emili Montserrat*
Department of Hematology and the Hematopathology Unit, Institute of Hematology and Oncology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Barcelona, Spain
* Corresponding author; email: emontse{at}clinic.ub.es.
We analyzed minimal residual disease (MRD) by consensus PCR, quantitative PCR (qPCR), and flow cytometry in 40 chronic lymphocytic leukemia (CLL) patients submitted to stem cell transplantation. 97.4%, 89% and 100% of the patients could be studied by consensus PCR, qPCR, and flow cytometry, respectively. Overall, 164 of 248 samples were MRD negative by consensus PCR. Among those, CLL cells were detected by qPCR and by flow cytometry in 47% (77/164) and 23% (39/164) of the samples, respectively. All 84 PCR positive samples had detectable CLL cells by qPCR and flow cytometry. A good correlation was seen between MRD levels by flow cytometry and by qPCR (n: 254, r: 0.826; p< 0.001). 15/25 autografted patients relapsed, with increasing levels of MRD being observed before relapse in all of them. MRD detection within the first six months after autologous transplantation identified patients with a high relapse risk. In contrast, in allografted patients (n=15) MRD did not correlate with outcome. In conclusion, quantitative methods to assess MRD (flow cytometry and qPCR) are more accurate than consensus PCR to predict clinical evolution. These results might be useful to investigate treatments aimed at preventing relapse in CLL patients having received an autograft.

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