Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia

التفاصيل البيبلوغرافية
العنوان: Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia
المؤلفون: Stefano Volpetti, Renato Fanin, Marianna Chiozzotto, Anna Candoni, Erica Simeone, Roberto Gallina, Eleonora Toffoletti
المصدر: Clinical Transplantation. 25:308-316
بيانات النشر: Wiley, 2011.
سنة النشر: 2011
مصطلحات موضوعية: Oncology, Transplantation, medicine.medical_specialty, business.industry, fungi, Myeloid leukemia, medicine.disease, Minimal residual disease, Leukemia, Haematopoiesis, medicine.anatomical_structure, Real-time polymerase chain reaction, hemic and lymphatic diseases, Internal medicine, Immunology, medicine, Bone marrow, Stem cell, business
الوصف: Candoni A, Toffoletti E, Gallina R, Simeone E, Chiozzotto M, Volpetti S, Fanin R. Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin Transplant 2011: 25: 308–316. © 2010 John Wiley & Sons A/S. Abstract: WT1 is well-known to be a panleukemic marker that is expressed in 90% of acute myeloid leukemias (AML). Quantification of WT gene expression in bone marrow (BM) samples may be useful as a marker of minimal residual disease (MRD) during and after treatment for early prediction of relapse. We evaluated the validity of this AML-MRD marker after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). The quantitative assessment of WT1 expression by real-time quantitative PCR (RQ-PCR) was measured in 25 patients (pts) with AML at diagnosis, at the time of RIC-SCT and after transplant at precise time points. All pts showed high WT1 levels at diagnosis with a mean of 4895 (SD 4462) and a median of 3679 (range 454–16 853) copies WT1/104 ABL. At transplant, 18/25 pts (72%) were in complete cytologic remission (CcR) and 7/25 (28%) had refractory AML. At the pre-SCT evaluation, BM samples from pts transplanted in CcR showed significantly lower WT1 expression levels compared to the samples from pts with refractory AML (p = 0.002). Median follow-up after RIC-SCT was 18 months (range 2–54). On 18 pts transplanted in CcR, those (17/18) who maintained CcR after RIC-SCT displayed a WT1 copy number persistently low during all the follow-up period. In patients who received RIC-SCT with active disease obtaining a sustained CcR after transplant (3/25), WT1 levels decreased to normal range in the first two months after RIC-SCT and remained low through the entire study period. All pts who relapsed after RIC-SCT (4/25) had a high WT1 copy number before the cytologic relapse. In 50% of these cases, an increase in WT1 expression was documented before molecular chimerism decreasing. With this experience, taking into account the limited number of pts, we confirmed a concordance between WT1 expression levels (measured by RQ-PCR at precise and sequential time points) and status of AML before and after RIC-SCT and we found a concordance between WT1 expression levels and hematopoietic chimerism status. Our data suggest that, in the RIC-SCT setting, the sequential and quantitative analysis of WT1 may be useful as a leukemia marker for monitoring MRD and as a predictor of overt AML cytologic relapse.
تدمد: 0902-0063
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::d42ef63ddc1bef2a9c6fc5d8da0744a9
https://doi.org/10.1111/j.1399-0012.2010.01251.x
حقوق: CLOSED
رقم الأكسشن: edsair.doi...........d42ef63ddc1bef2a9c6fc5d8da0744a9
قاعدة البيانات: OpenAIRE