Results of two consecutive treatment protocols in Polish children with acute lymphoblastic leukemia

Abstract

The aim of the study was to retrospectively compare the effectiveness of the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols and the distribution of risk groups by the two protocols after minimal residual disease (MRD) measurement as well as its impact on survival. We reviewed the medical records of 3248 patients aged 1–18 years with newly diagnosed ALL who were treated in 14 hemato-oncological centers between 2002 and 2018 in Poland. The overall survival (OS) of 1872 children with ALL treated with the ALL IC 2002 protocol was 84% after 3 years, whereas the OS of 1376 children with ALL treated with the ALL IC 2009 protocol was 87% (P < 0.001). The corresponding event-free survival rates were 82% and 84% (P = 0.006). Our study shows that the ALL IC-BFM 2009 protocol improved the results of children with ALL compared to the ALL IC-BFM 2002 protocol in Poland. This analysis confirms that MRD marrow assessment on day 15 of treatment by FCM-MRD is an important predictive factor.

Prognostic significance of IKZF1 deletions and IKZF1plus profile in children with B‐cell precursor acute lymphoblastic leukemia treated according to the ALL‐IC BFM 2009 protocol

“…The study comprised 373 pediatric patients, aged 0–18 years, with newly‐diagnosed BCP‐ALL. All were treated between 2010 and 2016 according to ALL‐IC BFM 2009 protocol in the 13 clinical centers of the Polish Pediatric Leukemia/Lymphoma Study Group 5 . Patients diagnosed with T‐cell and mature B‐cell ALL, as well as those who carried KMT2A/AFF1 (formerly myeloid/lymphoid or mixed‐lineage leukemia ( MLL)/AF4 ) or Breakpoint Cluster Region ( BCR)/ABL1 rearrangements, were excluded from the study.…”

“…The median age at diagnosis was 4.5 years (IQR: 2.9–7.1) and median follow‐up was 6.7 years (IQR: 5.7–7.4). The allocation of patients to risk groups was based on the criteria stated in the ALL‐IC BFM 2009 protocol 5 . Additionally, patients were allocated among risk groups defined by MRD at day 15 value (MRD15; standard risk group with MRD15 < 0.1% (MRD‐SR), intermediate risk group with 10.0% > MRD15 ≥ 0.1% (MRD‐IR) and high‐risk group with MRD15 ≥ 10.0% (MRD‐HR)).…”

“…Three highly‐specific and sensitive methodologies for MRD assessment are widely used in ALL diagnostics: real‐time quantitative polymerase chain reaction of fusion gene transcripts or breakpoints, (RQ‐PCR)–based detection of clonal immunoglobulin and T‐cell receptor gene rearrangements, and multiparameter flow cytometric (FC) immunophenotyping 4 . Whereas the FC‐measured MRD (FC‐MRD) value at day 15 of the induction protocol correlates with relapse free survival (RFS) in childhood BCP‐ALL, 3,5 PCR‐measured MRD (PCR‐MRD) level effectively predicts relapse when measured at day 33 of the initial chemotherapy regimen 6,7 . Moreover, the kinetics of leukemic cell clearance, translating into MRD distribution, significantly differs according to ALL genetic subtype 8,9 …”

Genomic Analyses of Pediatric Acute Lymphoblastic Leukemia Ph+ and Ph-Like—Recent Progress in Treatment

“…Although current treatment strategies are becoming increasingly successful, the most frequent cause of treatment failure is relapse. Cumulative relapse risk is 9.3-20.6%, and the outcome prognosis after a relapse is poor [6][7][8]. Several studies have clearly demonstrated that minimal residual disease (MRD) also has a crucial predictive role in ALL Ph+ [9][10][11][12].…”

A Novel Method for the Evaluation of Bone Marrow Samples from Patients with Pediatric B-Cell Acute Lymphoblastic Leukemia—Multidimensional Flow Cytometry

“…Acute lymphoblastic leukemia (ALL) is the most common pediatric malignant disease with an annual incidence of approximately 3.5/100,000 children worldwide; however, the overall 3-year survival rate can be as high as 87% if proper treatment is applied [1,2]. The 2016 modification of the World Health Organization (WHO) classification categories ALL based on recurrent genetic abnormalities which affect the characteristics of the disease and also determine the outcome and therapeutic decisions [3][4][5].…”