Abstract
BackgroundAssessment 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.MethodsIn 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.ResultsIn 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.ConclusionsIn 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.
Highlights
Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies
All patients with acute lymphoblastic leukemia (ALL) irrespective of MRD status benefit from total body irradiation (TBI)-based conditioning in the myeloablative setting
As ALL patients rarely receive reducedintensity conditioning, we explored if MRD detectable before allogeneic hematopoietic cell transplantation (HCT) for ALL is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning
Summary
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. 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. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured post-induction or consolidation is increasingly used to guide further therapy [1]. The prognostic value of MRD measured prior to allogeneic hematopoietic cell transplantation (HCT) on its outcomes was first observed in small retrospective [2, 3] and prospective [4] studies of children and adolescents and later in adults [5,6,7], and confirmed in a recent meta-analysis [8]. As ALL patients rarely receive reducedintensity conditioning, we explored if MRD detectable before allogeneic HCT for ALL is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning
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