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

      Influence of Minimal Residual Disease at Day 15 of Induction Therapy on Survival of Children with Acute Lymphoblastic Leukemia

      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

          Objective.

          The aim of the study was to evaluate the impact of minimal residual disease (MRD) on day 15 of induction therapy (d15) on the treatment outcome in children with acute lymphoblastic leukemia (ALL).

          Materials and Methods.

          The study included 74 patients (1-18 years) with ALL, who were treated at the Pediatric Clinic of the University Clinical Center Banja Luka from January 2011 to May 2021. All patients were treated according to ALL IC-BFM 2009 protocol. MRD on bone marrow was assessed d15, using the multiparameter flow cytometry method (FCM).

          Results.

          Of all, 59.46% of patients had MRD d15 0.1−10%, MRD<0.1% had 18.92% of patients, and 21.62% had MRD >10%. Patients with the lowest MRD had the highest 5-year overall survival (OS) and event-free survival (89.5% and 91% respectively) and the lowest cumulative risk for relapse or death (9.7% and 8.1%), in contrast to patients with MRD>10% in whom OS was 80.0%, and the risk of recurrence is 20%. Predicted MRD d15 was significantly associated with prednisone response assessed in the peripheral blood on day 8 (P<0.001) and statistically significantly positive correlation (r=0.498; P<0.001) was found.

          Conclusion.

          MRD measurement d15 has a great prognostic significance for patients in the standard and high risk groups, but not for patients in the intermediate risk group. The introduction of additional testing is necessary for better identification of patients with an increased risk of disease recurrence.

          Related collections

          Most cited references31

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

          Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration.

          To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.
            Bookmark
            • 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

              Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial.

              Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL) during remission. We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. Between Oct 1, 2003 and June 30, 2011, consecutive children and young adults (aged 1-25 years) with ALL from the UK and Ireland were recruited. Eligible patients were categorised into clinical standard, intermediate, and high risk groups on the basis of a combination of National Cancer Institute (NCI) criteria, cytogenetics, and early response to induction therapy, which was assessed by bone marrow blast counts taken at days 8 (NCI high-risk patients) and 15 (NCI standard-risk patients) after induction began. Clinical standard-risk and intermediate-risk patients were assessed for MRD. Those classified as MRD low risk (undetectable MRD at the end of induction [day 29] or detectable MRD at day 29 that became undetectable by week 11) were randomly assigned to receive one or two delayed intensification courses. Patients had received induction, consolidation, and interim maintenance therapy before they began delayed intensification. Delayed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alternate weeks), and doxorubicin for 3 weeks; and 4 weeks of cyclophosphamide and cytarabine. Computer randomisation was done with stratification by MRD result and balancing for sex, age, and white blood cell count at diagnosis by method of minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcome was event-free survival (EFS), which was defined as time to relapse, secondary tumour, or death. Our aim was to rule out a 7% reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses. Analyses were by intention to treat. This trial is registered, number ISRCTN07355119. Of 3207 patients registered in the trial overall, 521 MRD low-risk patients were randomly assigned to receive one (n=260) or two (n=261) delayed intensification courses. Median follow-up of these patients was 57 months (IQR 42-72). We recorded no significant difference in EFS between the group given one delayed intensification (94·4% at 5 years, 95% CI 91·1-97·7) and that given two delayed intensifications (95·5%, 92·8-98·2; unadjusted odds ratio 1·00, 95% CI 0·43-2·31; two-sided p=0·99). The difference in 5-year EFS between the two groups was 1·1% (95% CI -5·6 to 2·5). 11 patients (actuarial relapse at 5 years 5·6%, 95% CI 2·3-8·9) given one delayed intensification and six (2·4%, 0·2-4·6) given two delayed intensifications relapsed (p=0·23). Three patients (1·2%, 0-2·6) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification (p=0·08). We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects; however, the second delayed intensification course was associated with one (<1%) treatment-related death, and 74 episodes of grade 3 or 4 toxic effects in 45 patients (17%). Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy. Medical Research Council and Leukaemia and Lymphoma Research. Copyright © 2013 Elsevier Ltd. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                Role: Conception and designRole: Revising it critically for important intellectual conceptRole: Approved final version of the manuscript
                Role: Acquisition, analysis and interpretation of dataRole: Drafting the article
                Role: Acquisition, analysis and interpretation of dataRole: Drafting the article
                Journal
                Acta Med Acad
                Acta Med Acad
                Acta Medica Academica
                Academy of Sciences and Arts of Bosnia and Herzegovina (Bosnia and Herzegovina )
                1840-1848
                1840-2879
                2023
                : 52
                : 3
                : 153-160
                Affiliations
                [1 ]Children’s Hospital, University Clinical Centre of the Republic of Srpska, Banja Luka, Republic of Srpska, Bosnia and Herzegovina
                [2 ]Faculty of medicine, University of Banja Luka, Banja Luka, Republic of Srpska, Bosnia and Herzegovina
                Author notes
                Correspondence: predojevicjelica5@ 123456gmail.com ; biljanadjbanjac@ 123456gmail.com ; Tel.: + 387 51 342339; Tel.: + 387 65 817191
                Article
                AMA-52-153
                10.5644/ama2006-124.427
                10945324
                38407081
                40da31b8-310d-481c-a688-89671e23a66f
                Copyright © 2023 Academy of Sciences and Arts of Bosnia and Herzegovina

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 October 2023
                : 28 December 2023
                Categories
                Original Research Study

                minimal residual disease,acute lymphoblastic leukemia,children,outcome

                Comments

                Comment on this article