17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning.

          Methods

          In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18–72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors.

          Results

          In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02–1.39), 1.26 (1.1–1.44), and 1.51 (1.26–1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62–0.90), 0.70 (0.60–0.82), and 0.60 (0.49–0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients.

          Conclusions

          In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: found
          • Article: not found

          Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis.

          Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Solid cancers after bone marrow transplantation.

            The late effects of bone marrow transplantation, including cancer, need to be determined in a large population at risk. We studied 19,229 patients who received allogeneic transplants (97.2 percent) or syngeneic transplants (2.8 percent) between 1964 and 1992 at 235 centers to evaluate the risk of the development of a new solid cancer. Risk factors relating to the patient, the transplant, and the course after transplantation were evaluated. The transplant recipients were at significantly higher risk of new solid cancers than the general population (observed cases, 80; ratio of observed to expected cases, 2.7; P<0.001). The risk was 8.3 times higher than expected among those who survived 10 or more years after transplantation. The cumulative incidence rate was 2.2 percent (95 percent confidence interval, 1.5 to 3.0 percent) at 10 years and 6.7 percent (95 percent confidence interval, 3.7 to 9.6 percent) at 15 years. The risk was significantly elevated (P<0.05) for malignant melanoma (ratio of observed to expected cases, 5.0) and cancers of the buccal cavity (11.1), liver (7.5), brain or other parts of the central nervous system (7.6), thyroid (6.6), bone (13.4), and connective tissue (8.0). The risk was higher for recipients who were younger at the time of transplantation than for those who were older (P for trend <0.001). In multivariate analyses, higher doses of total-body irradiation were associated with a higher risk of solid cancers. Chronic graft-versus-host disease and male sex were strongly linked with an excess risk of squamous-cell cancers of the buccal cavity and skin. Patients undergoing bone marrow transplantation have an increased risk of new solid cancers later in life. The trend toward an increased risk over time after transplantation and the greater risk among younger patients indicate the need for life-long surveillance.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission.

                Bookmark

                Author and article information

                Contributors
                +44(0)-20-3313-8117 , jiri@pavlu.co.uk
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                23 October 2019
                23 October 2019
                2019
                : 12
                : 108
                Affiliations
                [1 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Centre for Haematology, , Imperial College London at Hammersmith Hospital, ; Du Cane Road, London, W12 0HS UK
                [2 ]GRID grid.492743.f, Department of Haematology, , EBMT Paris Study Office/CEREST-TC/Saint Antoine Hospital, ; Paris, France
                [3 ]ISNI 0000 0000 9950 5666, GRID grid.15485.3d, Stem Cell Transplantation Unit, , HUCH Comprehensive Cancer Center, ; Helsinki, Finland
                [4 ]ISNI 0000 0001 2300 6614, GRID grid.413328.f, Hematology–BMT, , Saint Louis Hospital, ; Paris, France
                [5 ]ISNI 0000 0004 0639 4004, GRID grid.413875.c, Service des Maladies du Sang, , Hopital Claude Huriez, CHRU Lille, ; Lille, France
                [6 ]GRID grid.429222.d, Department of Hematology, , the First Affiliated Hospital of Soochow University, ; Soochow, China
                [7 ]Délpesti Centrumkórház–Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary
                [8 ]GRID grid.410567.1, University Hospital Basel, ; Basel, Switzerland
                [9 ]ISNI 0000 0001 0262 7331, GRID grid.410718.b, Department of Bone Marrow Transplantation, , University Hospital of Essen, ; Essen, Germany
                [10 ]ISNI 0000 0001 2191 4301, GRID grid.415310.2, Department of Oncology, , King Faisal Specialist Hospital and Research Center, ; Riyadh, Saudi Arabia
                [11 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Bone Marrow Transplantation Centre, , University Hospital Eppendorf, ; Hamburg, Germany
                [12 ]ISNI 0000 0001 0288 2594, GRID grid.411430.3, Service d’hématologie, , Centre Hospitalier Lyon Sud, ; Lyon, France
                [13 ]Zavod za hematologiju, Klinika za unutarnje bolesti, Zagreb, Croatia
                [14 ]ISNI 0000 0004 0540 2543, GRID grid.418165.f, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, ; Gliwice, Poland
                [15 ]ISNI 0000 0001 2107 2845, GRID grid.413795.d, Division of Hematology and Bone Marrow Transplantation, , Chaim Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, ; Ramat Gan, Israel
                Author information
                http://orcid.org/0000-0001-5219-5637
                Article
                790
                10.1186/s13045-019-0790-x
                6813121
                31647022
                c6588137-0bc5-4868-8277-7ed9ed0daf03
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 July 2019
                : 10 September 2019
                Funding
                Funded by: National Institute for Health Research Biomedical Research Centre based at Imperial College London
                Award ID: N/A
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                measurable residual disease,allogeneic hematopoietic cell transplantation,acute lymphoblastic leukemia,allogeneic,myeloablative conditioning,total body irradiation

                Comments

                Comment on this article