Format

Send to

Choose Destination
J Hematol Oncol. 2019 Oct 23;12(1):108. doi: 10.1186/s13045-019-0790-x.

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.

Author information

1
Centre for Haematology, Imperial College London at Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK. jiri@pavlu.co.uk.
2
Department of Haematology, EBMT Paris Study Office/CEREST-TC/Saint Antoine Hospital, Paris, France.
3
Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland.
4
Hematology-BMT, Saint Louis Hospital, Paris, France.
5
Service des Maladies du Sang, Hopital Claude Huriez, CHRU Lille, Lille, France.
6
Department of Hematology, the First Affiliated Hospital of Soochow University, Soochow, China.
7
Délpesti Centrumkórház-Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary.
8
University Hospital Basel, Basel, Switzerland.
9
Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany.
10
Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
11
Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany.
12
Service d'hématologie, Centre Hospitalier Lyon Sud, Lyon, France.
13
Zavod za hematologiju, Klinika za unutarnje bolesti, Zagreb, Croatia.
14
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
15
Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, Ramat Gan, Israel.

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.

KEYWORDS:

Acute lymphoblastic leukemia; Allogeneic; Allogeneic hematopoietic cell transplantation; Measurable residual disease; Myeloablative conditioning; Total body irradiation

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center