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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 3; pp. 396 - 402
• Main Authors: Sanchez-Garcia, J, Serrano, J, Serrano-Lopez, J, Gomez-Garcia, P, Martinez, F, Garcia-Castellano, J M, Rojas, R, Martin, C, Rodriguez-Villa, A, Molina-Hurtado, J R, Alvarez, M A, Casaño, J, Torres-Gomez, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2013; Nature Publishing Group
• Subjects: 631/1647/1407/1492; 631/250/1904; 631/532/1542; 692/699/67/1990/283/2125; Adolescent; Analysis; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Care and treatment; Cell Biology; Child; Cohort Studies; Disease-Free Survival; Female; Flow cytometry; Flow Cytometry - methods; Follow-Up Studies; Hematologic and hematopoietic diseases; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Hemopoiesis; Humans; Internal Medicine; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (mononuclear); Lymphatic leukemia; Male; Medical sciences; Medicine; Medicine & Public Health; Minimal residual disease; Myeloproliferative disorders; Neoplasm, Residual; original-article; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - surgery; Prognosis; Proportional Hazards Models; Public Health; Rank tests; Retrospective Studies; Stem cell transplantation; Stem Cells; Survival; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Transplants & implants; Treatment Outcome; ALL; multiparameter flow cytometry; allogeneic transplantation; Human; Flow cytometry; Prognosis; Minimal residual disease; Quantization; Malignant hemopathy; Treatment; Allogeneic hematopoietic stem cell transplantation; Lymphoproliferative syndrome; Graft; Myelosuppression; Acute lymphocytic leukemia; Cancer
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2012.147

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.