Autologous hematopoietic stem cell transplantation (ASCT) is a curative option alternative to allogeneic transplantation for patients with acute myeloid leukemia (AML). Relapse after ASCT can be due to contamination with leukemic blasts of autologous peripheral blood stem cells (PBSCs) collected by leukapheresis (LK). Identification and quantification of a minimal residual disease (MRD) marker in PBSCs could be relevant in determining the relapse risk after ASCT. High levels of the WT1 gene transcript in bone marrow of AML patients after treatment completion predict disease relapse. We evaluated WT1 transcript levels in autologous PBSC from LK used for ASCT in 30 consecutive AML patients in complete remission (CR) and established a correlation with clinical outcome. At diagnosis, all patients had WT1 overexpression. All patients were in morphological and genetic CR at the time of PBSC collection and before ASCT. Real-time quantitative PCR of WT1 was performed in samples of each LK, using TaqMan technology on RNA from mononucleated cells. The median WT1 transcript level in the PBSC graft (WT1-LK) of patients who relapsed was significantly higher than of those who did not relapse after transplantation (P <.0001). We defined a cut-off level of 80 WT1-LK copies/ABL 10e4 copies to discriminate between positive and negative PBSC grafts. The cut-off level was strongly associated with disease recurrence, DFS and OS. Our study represents the largest series of patients evaluating WT1 as a marker of MRD in PBSC LK products using a completely standardized real-time WT1-reverse transcriptase-PCR based assay. These data, if confirmed by prospective study, will help to determine an individual patient's adapted postremission allocation strategy.

Wilms' Tumor Gene 1 Transcript Levels in Leukapheresis ofPeripheral Blood Hematopoietic Cells Predict Relapse Risk inPatients Autografted for Acute Myeloid Leukemia / Messina, C.; Candoni, A.; Carrabba, M. G.; Tresoldi, C.; Sala, E.; Tassara, M.; Crippa, A.; Peccatori, J.; Assanelli, A.; Gattillo, S.; Bellio, L.; Fanin, R.; Ciceri, F.; Bernardi, M.. - In: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION. - ISSN 1083-8791. - 20:10(2014), pp. 1586-1591. [10.1016/j.bbmt.2014.06.017]

Wilms' Tumor Gene 1 Transcript Levels in Leukapheresis ofPeripheral Blood Hematopoietic Cells Predict Relapse Risk inPatients Autografted for Acute Myeloid Leukemia

Candoni A.;
2014

Abstract

Autologous hematopoietic stem cell transplantation (ASCT) is a curative option alternative to allogeneic transplantation for patients with acute myeloid leukemia (AML). Relapse after ASCT can be due to contamination with leukemic blasts of autologous peripheral blood stem cells (PBSCs) collected by leukapheresis (LK). Identification and quantification of a minimal residual disease (MRD) marker in PBSCs could be relevant in determining the relapse risk after ASCT. High levels of the WT1 gene transcript in bone marrow of AML patients after treatment completion predict disease relapse. We evaluated WT1 transcript levels in autologous PBSC from LK used for ASCT in 30 consecutive AML patients in complete remission (CR) and established a correlation with clinical outcome. At diagnosis, all patients had WT1 overexpression. All patients were in morphological and genetic CR at the time of PBSC collection and before ASCT. Real-time quantitative PCR of WT1 was performed in samples of each LK, using TaqMan technology on RNA from mononucleated cells. The median WT1 transcript level in the PBSC graft (WT1-LK) of patients who relapsed was significantly higher than of those who did not relapse after transplantation (P <.0001). We defined a cut-off level of 80 WT1-LK copies/ABL 10e4 copies to discriminate between positive and negative PBSC grafts. The cut-off level was strongly associated with disease recurrence, DFS and OS. Our study represents the largest series of patients evaluating WT1 as a marker of MRD in PBSC LK products using a completely standardized real-time WT1-reverse transcriptase-PCR based assay. These data, if confirmed by prospective study, will help to determine an individual patient's adapted postremission allocation strategy.
2014
20
10
1586
1591
Wilms' Tumor Gene 1 Transcript Levels in Leukapheresis ofPeripheral Blood Hematopoietic Cells Predict Relapse Risk inPatients Autografted for Acute Myeloid Leukemia / Messina, C.; Candoni, A.; Carrabba, M. G.; Tresoldi, C.; Sala, E.; Tassara, M.; Crippa, A.; Peccatori, J.; Assanelli, A.; Gattillo, S.; Bellio, L.; Fanin, R.; Ciceri, F.; Bernardi, M.. - In: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION. - ISSN 1083-8791. - 20:10(2014), pp. 1586-1591. [10.1016/j.bbmt.2014.06.017]
Messina, C.; Candoni, A.; Carrabba, M. G.; Tresoldi, C.; Sala, E.; Tassara, M.; Crippa, A.; Peccatori, J.; Assanelli, A.; Gattillo, S.; Bellio, L.; Fanin, R.; Ciceri, F.; Bernardi, M.
File in questo prodotto:
File Dimensione Formato  
VOR_Wilms' Tumor Gene 1 Transcript Levels in Leukapheresis of Peripheral Blood Hematopoietic Cells Predict Relapse Risk in Patients Autografted for Acute Myeloid Leukemia.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 401.87 kB
Formato Adobe PDF
401.87 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1294155
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 21
social impact