ABCG2 overexpression in patients with acute myeloid leukemia: Impact on stem cell transplantation outcome
| Autor: | Daniela, Damiani, Mario, Tiribelli, Antonella, Geromin, Angela, Michelutti, Margherita, Cavallin, Alessandra, Sperotto, Renato, Fanin |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Transplantation Conditioning Adolescent Remission Induction Hematopoietic Stem Cell Transplantation Gene Expression Antineoplastic Agents Middle Aged Prognosis Survival Analysis Neoplasm Proteins Leukemia Myeloid Acute Treatment Outcome Recurrence ATP Binding Cassette Transporter Subfamily G Member 2 Humans Transplantation Homologous ATP-Binding Cassette Transporters Female Aged Retrospective Studies |
| Zdroj: | American journal of hematology. 90(9) |
| ISSN: | 1096-8652 |
| Popis: | ABGG2 protein overexpression in acute myeloid leukemia (AML) has been associated with poor response to conventional chemotherapy and increased relapse risk. No data are available on the role of allogeneic stem cell transplantation (SCT) in reversing its negative prognostic role. We have reviewed the outcome of 142 patients with high risk AML who underwent allogeneic SCT in complete remission (n = 94) or with active disease (n = 48). Patients with ABCG2 overexpression at AML diagnosis have lower leukemia free survival (LFS) and increased cumulative incidence of relapse (CIR) compared with ABCG2- patients (5-year LFS 50% vs. 65%, P = 0.01; 5-year CIR 46% vs. 27%, P = 0.003). Five-year overall survival was not significantly different between ABCG2+ and ABCG2- patients (39% vs. 51%, P = 0.1). However, if we consider only disease-related deaths, ABCG2 maintains its negative role (64% vs. 78%, P = 0.018). The negative impact of ABCG2 overexpression was higher in patients undergoing SCT in CR compared with patients receiving transplant with active disease. Conditioning regimen did not abrogate the effect of ABCG2 overexpression, as CIR was higher in ABCG2+ patients receiving both myeloablative (44% vs. 22%, P = 0.018) or reduced intensity conditioning (50% vs. 32%, P = 0.03). In conclusion, ABCG2 overexpression at AML diagnosis identifies a subset of patients with poor outcome also after allogeneic SCT, mainly in terms of higher relapse rates. Prospective studies employing conditioning drugs or post-transplant strategies able to target ABCG2 are needed to maximize the curative potential of stem cell transplantation. |
| Databáze: | OpenAIRE |
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