Abstract

BackgroundIn acute lymphoblastic leukemia (ALL), the presence of minimal residual disease (MRD) after induction/consolidation chemotherapy is a strong prognostic factor for subsequent relapse and mortality. Accordingly, European clinical guidelines and protocols recommend testing patients who achieve a complete hematological remission (CR) for MRD for the purpose of risk stratification. The aim of this study was to provide quantitative information regarding real-world clinical practice for MRD testing in five European countries.MethodsA web-based survey was conducted in March/April 2017 in France, Germany, Italy, Spain, and the UK. The survey was developed after consultation with specialist clinicians and a review of published literature. Eligible clinicians (20 per country; 23 in Spain) were board-certified in hemato-oncology or hematology, had at least five years’ experience in their current role after training, had treated at least two patients with B-cell precursor ALL in the 12 months before the survey or at least five patients in the last five years, and had experience of testing for MRD in clinical practice.ResultsMRD testing is now standard practice in the treatment of adult ALL across the five European countries, with common use of recent treatment protocols which specify testing. Respondents estimated that, among clinicians in their country who conduct MRD testing, 73% of patients in first CR (CR1) and 63% of patients in second or later CR (CR2+) are tested for MRD. The median time point reported as most commonly used for the first MRD test, to establish risk status and to determine a treatment plan was four weeks after the start of induction therapy. The timing and frequency of tests is similar across countries. An average of four or five post-CR1 tests per patient in the 12 months after the first MRD test were reported across countries.ConclusionsThis comprehensive study of MRD testing patterns shows consistent practice across France, Germany, Italy, Spain, and the UK with respect to the timing and frequency of MRD testing, aligning with use of national protocols. MRD testing is used in clinical practice also in patients who reach CR2 + .

Highlights

  • In acute lymphoblastic leukemia (ALL), the presence of minimal residual disease (MRD) after induction/ consolidation chemotherapy is a strong prognostic factor for subsequent relapse and mortality

  • Most respondents reported that their institution was a university hospital (66%, n = 68), and 78% (n = 80) reported that their institution participated in research conducted by a European ALL study group or in other registered trials

  • Respondents reported that a mean of 70% (SD 36%; ranging from 50% in the UK to 89% in Spain) of their adult patients receiving front-line therapy for B-precursor Philadelphia chromosome (Ph)– ALL had their treatment pathway determined by a protocol

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Summary

Introduction

In acute lymphoblastic leukemia (ALL), the presence of minimal residual disease (MRD) after induction/ consolidation chemotherapy is a strong prognostic factor for subsequent relapse and mortality. European clinical guidelines and protocols recommend testing patients who achieve a complete hematological remission (CR) for MRD for the purpose of risk stratification. After front-line chemotherapy, the majority of adults with ALL achieve hematological complete remission (CR, defined as < 5% lymphoid blasts in the bone marrow based on a morphologic assessment) [3]. Leukemic cells may remain in the bone marrow below the threshold of detection of conventional morphologic methods; this is termed minimal residual disease (MRD) [4]. MRD testing uses biomarkers of malignant cells to identify trace levels in bone marrow samples from patients who have achieved CR, using flow cytometry or polymerase chain reaction (PCR)-based techniques [5].

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