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Allografting

Quantification of minimal residual disease levels by flow cytometry at time of transplant predicts outcome after myeloablative allogeneic transplantation in ALL

Bone Marrow Transplantation volume 48, pages 396–402 (2013)Cite this article

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Abstract

The potential impact on patient outcome of different Minimal residual disease (MRD) levels at time of transplant in patients with lymphoblastic leukemia undergoing allogeneic hematopoietic SCT (HSCT) remains uncertain. In this study, we quantified MRD levels at time of transplant using multiparameter flow cytometry (MFC). Mononuclear cells from marrow aspirates were obtained from 102 adult and child patients before their conditioning regimen. Quantification of MRD levels was carried out by detecting patient-specific leukemia-associated immunophenotypes using four-color MFC. Thirty patients exhibited measurable levels of MRD at the time of transplant, with low levels (0.01 to ⩽0.1%) in 12 cases, intermediate levels (>0.1 to ⩽1%) in 8 cases and high levels (>1%) in 10 cases. The leukemia-free survival (LFS) rates were 65.9±7.0%, 42.9±15.7% and 0% for negative, low levels ⩽0.1% and intermediate-high levels >0.1%, respectively (P<0.001, log-rank test). Overall survival (OS) was 52.3±7.6%, 28.6±13.8% and 0% for MRD-negative, low levels ⩽0.1% and intermediate-high levels >0.1%, respectively (P<0.001, log-rank test). Multivariate Cox analysis confirmed that detection of leukemia cells by flow cytometry at transplant was the most significantly adverse factor for OS, LFS and EFS after transplant.

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Acknowledgements

This study was supported by a grant from Ministerio de Ciencia e Innovacion BFU2009-11826, by Asociacion Medicina e Investigación (AMI) and by a donation form ‘Instituto Roche para las soluciones Integrales en Salud’. J Serrano-Lopez has a fellowship from Spanish Foundation of Hematology and Hemotherapy (FEHH) and Fundación Reina Sofía de Córdoba.

Author contributions: JS-G, JSL and AT-G designed the study. JS-G, JS-L and JMG-C performed cytometric assays. PG-G, FM, RR, CM, AR-V, JRM-H and JC collected patient samples and clinical data. JS-G, JSL and MAA performed statistical analyses and interpreted data. JS-G wrote the manuscript. All authors critically reviewed the manuscript and gave their final approval. JS-G is responsible of figures and tables.

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Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation Department, University Hospital ‘Reina Sofia’, Cordoba, Spain

    J Sanchez-Garcia, J Serrano, J Serrano-Lopez, P Gomez-Garcia, F Martinez, J M Garcia-Castellano, R Rojas, C Martin, A Rodriguez-Villa, J R Molina-Hurtado, M A Alvarez, J Casaño & A Torres-Gomez

  2. Instituto Maimonides Investigation Biomedica (IMIBIC), University Hospital ‘Reina Sofia’, Cordoba, Spain

    J Sanchez-Garcia, J Serrano, J Serrano-Lopez & A Torres-Gomez

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  1. J Sanchez-Garcia
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Correspondence to J Sanchez-Garcia.

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Sanchez-Garcia, J., Serrano, J., Serrano-Lopez, J. et al. Quantification of minimal residual disease levels by flow cytometry at time of transplant predicts outcome after myeloablative allogeneic transplantation in ALL. Bone Marrow Transplant 48, 396–402 (2013). https://doi.org/10.1038/bmt.2012.147

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