Haematologica, Vol 92, Issue 3, 315-322 doi:10.3324/haematol.10734
Copyright © 2007 by Ferrata Storti Foundation
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Acute Myeloid Leukemia

Using quantification of the PML-RAR{alpha} transcript to stratify the risk of relapse in patients with acute promyelocytic leukemia

Carlos Santamaría, Maria Carmen Chillón, Carina Fernández, Patricia Martín-Jiménez, Ana Balanzategui, Ramón García Sanz, Jesús F. San Miguel, Marcos-Gonzalez González

From the Servicio de Hematología, Hospital Universitario, Salamanca, Spain.

Correspondence: Ramón García Sanz, MD, PhD, Departament of Hematology, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain. E-mail: rgarcias{at}usal.es

Background and Objectives: The detection of PML-RAR{alpha} by real-time polymerase chain reaction (RQ-PCR) is becoming an important tool for monitoring minimal residual disease (MRD) in patients with acute promyelocytic leukemia (APL). However, its clinical value remains to be determined. Our aim was to analyze any associations between the risk of relapse and RQ-PCR results in different phases of treatment, comparing these data with those yielded by conventional qualitative reverse transcriptase-PCR.

Design and Methods: Follow-up samples from 145 APL patients treated with the PETHEMA protocols were evaluated by the RQ-PCR protocol (Europe Against Cancer program) and by the RT-PCR method (BIOMED-1 Concerted Action). Hematologic and molecular relapses and relapse-free survival were recorded. We then looked for associations between relapse risk and RQ-PCR results.

Results: After induction therapy, no association was found between positive RQ-PCR results and relapse. The PCR result here did not imply any change in the scheduled therapy. After the third consolidation course, two out of three cases with positive RQ-PCR relapsed in contrast to 16 out of 119 (13%) patients with negative RQ-PCR. During maintenance therapy and out-of treatment, all patients with >10 PML-RAR{alpha} normalized copy number (NCN) (n=19) relapsed while all patients with <1 NCN at the end of the study remained in hematologic remission (p<0.0001). In the intermediate group (NCN 1–10) (n=18), the relapse-free survival at 5 years was 60%. Hematologic relapses were predicted if a positive RQ-PCR result had been obtained in a follow-up sample within the previous 4 months.

Interpretation and Conclusions: Based on the information provided by RQ-PCR in samples obtained after the end of consolidation and subsequently, a relapse risk stratification could be established for APL patients. This stratification divides patients into three groups: those at high risk of relapse, those with an intermediate risk and those with a low risk of relapse.

Key words: acute promyelocytic leukemia, RQ-PCR, minimal residual disease.


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Francesco Lo-Coco, Emanuele Ammatuna, Miguel A. Sanz
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