Journal article
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.
- Pavlů J Centre for Haematology, Imperial College London at Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK. jiri@pavlu.co.uk.
- Labopin M Department of Haematology, EBMT Paris Study Office/CEREST-TC/Saint Antoine Hospital, Paris, France.
- Niittyvuopio R Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland.
- Socié G Hematology-BMT, Saint Louis Hospital, Paris, France.
- Yakoub-Agha I Service des Maladies du Sang, Hopital Claude Huriez, CHRU Lille, Lille, France.
- Wu D Department of Hematology, the First Affiliated Hospital of Soochow University, Soochow, China.
- Remenyi P Délpesti Centrumkórház-Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary.
- Passweg J University Hospital Basel, Basel, Switzerland.
- Beelen DW Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany.
- Aljurf M Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
- Kröger N Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany.
- Labussière-Wallet H Service d'hématologie, Centre Hospitalier Lyon Sud, Lyon, France.
- Perić Z Zavod za hematologiju, Klinika za unutarnje bolesti, Zagreb, Croatia.
- Giebel S Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
- Nagler A Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, Ramat Gan, Israel.
- Mohty M Department of Haematology, EBMT Paris Study Office/CEREST-TC/Saint Antoine Hospital, Paris, France.
- 2019-10-25
Published in:
- Journal of hematology & oncology. - 2019
Acute lymphoblastic leukemia
Allogeneic
Allogeneic hematopoietic cell transplantation
Measurable residual disease
Myeloablative conditioning
Total body irradiation
Adolescent
Adult
Aged
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Myeloablative Agonists
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Registries
Remission Induction
Retrospective Studies
Transplantation Conditioning
Transplantation, Homologous
Whole-Body Irradiation
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s13045-019-0790-x
- PMID 31647022
- Persistent URL
- https://sonar.ch/global/documents/53950
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