Day 15 and Day 33 Minimal Residual Disease Assessment for Acute Lymphoblastic Leukemia Patients Treated According to the BFM ALL IC 2009 Protocol: Single-Center Experience of 133 Cases

Abstract

Introduction: Childhood acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the acquisition of several genetic lesions in the lymphoid progenitors with subsequent proliferation advantage and lack of maturation. Along the years, it has been repeatedly shown that minimal residual disease (MRD) plays an important role in prognosis and therapy choice. The aim of the current study was to determine the prognostic role of MRD in childhood ALL patients in conjunction with other relevant patient and disease characteristics, thus showing the real-life scenario of childhood ALL. Patients and Methods: The retrospective study includes childhood ALL patients that were treated according to the BFM ALL IC 2009 between January 2016 and December 2018 at the Fundeni Clinical Institute, Bucharest, Romania. Results: None of the variables significantly influenced the induction-related death in our study. None of the variables independently predicted relapse-free survival (RFS) with the highest tendency for statistical significance being represented by poor prednisone response. Non-relapse mortality (NRM) was independently predicted by age, prednisone response, and day 33 flow cytometry-MRD (FCM-MRD). Overall survival (OS) was independently predicted by prednisone response and day 33 FCM-MRD. Event-free survival (EFS) was independently predicted by age, prednisone response, and day 33 FCM-MRD. Conclusion : Prednisone response, day 15 FCM-MRD, day 33 FCM-MRD, and the risk group represent the most important factors that in the current study independently predict childhood ALL prognosis.

Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group

“…The chemotherapeutic drug classes and the composition of the chemotherapy protocol at each time period were essentially the same for both regimens, i.e., diagnosis and assessment of sensitivity after 7 days of pretreatment with prednisone upon enrollment, continued initiation of VDLD (vincristine+dexamethasone+ L-asparaginase+daunorubicin) induced remission therapy, early intensive CAM (cyclophosphamide+cytarabine+6-mercaptopurine), mM (high-dose methotrexate + 6-mercaptopurine, or HR-1, HR-2, HR-3 all in two rounds), delayed intensive VDLD, CAM regimen (with 8 weeks of maintenance chemotherapy in between) in one or two rounds, and finally maintenance chemotherapy and regular intrathecal injections, with specific drug doses and risk assessment indicators in Ref ( 11 , 12 ).…”

Prognostic significance of CNSL at diagnosis of childhood B-cell acute lymphoblastic leukemia: A report from the South China Children’s Leukemia Group

“…The South China Children’s Leukemia Group (SCCLG)-ALL-2016 is a prospective, multi-institutional clinical trial involving 18 major hospitals/medical centers ( 9 , 10 ). We designed the SCCLG-ALL-2016 collaborative protocol based on the backbones of Berlin-Frankfurt-Münster (BFM) ALL-IC-2009 and Guangdong (GD)-2008-ALL ( 11 , 12 ). In this study, we aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the SCCLG-ALL-2016 trial.…”

Expression Patterns of Coagulation Factor XIII Subunit A on Leukemic Lymphoblasts Correlate with Clinical Outcome and Genetic Subtypes in Childhood B-cell Progenitor Acute Lymphoblastic Leukemia

“…We excluded patients of the Flow Low-risk (FLR) category because exact ratio of FXIII-A positive lymphoblasts below 0.1% could not be estimated due to the cytoplasmic expression of FXIII-A. The percentage of FXIII-A positive leukemic lymphoblasts of patients with Flow Medium-risk (FMR) and Flow High-risk (FHR) categories was significantly lower in Day 15 than in Day 0 samples (p < 0.001) [14]. FXIII-A expression of FXIII-A negative de novo cases did not change significantly by Day 15.…”

“…The consortium developed a multiparameter FC-based MRD detection method as a pilot project of ALL IC-BFM 2002 [13]. Result of mid-induction, day 15 bone marrow (BM) FC-MRD was incorporated in the risk assessment approach of the next ALLIC clinical trial, ALL IC-BFM 2009 (EuDract: 2010-019722-13, unpublished data) [14]. ALLIC FC laboratories became members of the International BFM Flow-network [8,15].…”