Bone Marrow WT1 Levels in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplasia: Clinically Relevant Time Points and 100 Copies Threshold Value


Por: Nomdedeu, JF, Esquirol, A, Carricondo, M, Pratcorona, M, Hoyos, M, Garrido, A, Rubio, M, Bussaglia, E, Garcia-Cadenas, I, Estivill, C, Brunet, S, Martino, R, Sierra, J

Publicada: 1 ene 2018
Resumen:
The outcome of allogeneic hematopoietic stem cell transplantation (HCT) in patients with myeloid malignancies is better in those without minimal residual disease (MRD) than in those with MRD+, as assessed by multiparametric flow cytometry (MPFC). WT1 quantitation also has been used to assess the probability of relapse in acute myelogenous leukemia (AML) treated with chemotherapy. We analyzed the clinical value of normalized bone marrow WT1 levels as a measure of the expanded myeloid progenitor compartment in a consecutive series of 193 adult patients with myeloid malignancies who underwent HCT. Bone marrow WT1 levels before the HCT, at the first bone marrow aspirate after infusion, and in the follow-up samples after HCT were determined by means of real-time PCR using the European LeukemiaNet normalized method. We sought to clarify the prognostic relevance in terms of overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse (CIR). Based on earlier experience in AML, we selected a threshold of 100 copies, defining 2 groups: patients with <100 WT1 copies and those with 100 copies. Patients with <100 WTI copies before HCT (median time, 36 days; range, 4 to 268 days) had a better OS, PFS, and CIR than those with 100 copies (40 +/- 1 versus 29 +/- 6 days, P = .004; 35 +/- 9 versus 26 +/- 6 days, P = .002; and 29 +/- 7 versus 37 +/- 6 days, P = .051). In the first bone marrow study after the HCT (median time, 42 days; range 14 to 157 days, respectively), patients with <100 WT1 copies also had better outcomes in terms of OS, PFS, and CIR (40 +/- 7 versus 31 +/- 9 days, P = .025; 36 +/- 7 versus 30 +/- 8 days, P=.004; and 29 +/- 6 days versus 54 +/- 9, P<.001, respectively). At this time point, bone marrrow samples with >100 copies also included patients who were negative for MRD as assessed by MPFC (19 of 32). During the HCT follow-up, patients with sustained WT1 levels <100 copies showed a marked benefit in terms of OS, PFS, and CIR even compared with those with only a single measurement >100 copies (mean, 68 +/- 11 versus 26 +/- 7 days, P < .001; 63 +/- 11 versus 20 +/- 8 days, P < .001; and 20 +/- 8 vs. 71 +/- 8 days, P <.001, respectively). Standardized bone marrow WT1 levels using a 100-copy threshold in samples obtained before HCT, at leukocyte recovery, and during follow-up provided relevant prognostic information in patients with myeloid malignacies submitted to HCT. (C) 2017 American Society for Blood and Marrow Transplantation.

Filiaciones:
Nomdedeu, JF:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Esquirol, A:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Dept,Hematopoiet Transplant Program, Barcelona, Spain

Carricondo, M:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Pratcorona, M:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Hoyos, M:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Garrido, A:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Dept,Hematopoiet Transplant Program, Barcelona, Spain

Rubio, M:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Bussaglia, E:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Garcia-Cadenas, I:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Dept,Hematopoiet Transplant Program, Barcelona, Spain

Estivill, C:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Lab, Barcelona, Spain

Brunet, S:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Dept,Hematopoiet Transplant Program, Barcelona, Spain

Martino, R:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Dept,Hematopoiet Transplant Program, Barcelona, Spain

Sierra, J:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, IIB St Pau & Jose Carreras Leukemia Res Inst, Hematol Dept,Hematopoiet Transplant Program, Barcelona, Spain
ISSN: 10838791





BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Editorial
ELSEVIER SCIENCE INC, STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 24 Número: 1
Páginas: 55-63
WOS Id: 000419933800010
ID de PubMed: 28939453
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