Re-Emergence of Minimal Residual Disease Detected by Flow Cytometry Predicts an Adverse Outcome in Pediatric Acute Lymphoblastic Leukemia

Wang, Yu; Xue, Yu-Juan; Jia, Yueping; Zuo, Ying‐Xi; Lu, Ai‐Dong; Zhang, Leping

doi:10.3389/fonc.2020.596677

Cited by 5 publications

(6 citation statements)

References 24 publications

(27 reference statements)

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“…In 37 children >1-year old with KMT2A + B-cell ALL in CR1, hHSCT using the Beijing Protocol has been shown to improve LFS (89.5 % vs. 52.2 %, respectively, p < 0.001) and reduce CIR (5.3 % vs. 74.1 %, respectively; p < 0.001) compared with no HSCT (64). In 150 paediatric patients who had minimal-residual disease (MRD) recurrence (≥0.01%), Wang et al demonstrated that hHSCT using the Beijing Protocol resulted in a lower 2-year CIR (23.3% vs. 64.0%, respectively; p < 0.001) and a higher OS rate (88.7% vs. 46.3%, respectively; p < 0.001) than did chemotherapy (65). Xu et al reported that 48 children with high-risk T-cell ALL who received hHSCT using the Beijing Protocol during CR1 exhibited higher LFS (65.7% vs. 26.0%, respectively; p = 0.008) and a lower relapse rate (19.8% vs. 56.7%, respectively; p = 0.014) than did patients transplanted when not in CR1, indicating that paediatric patients with T-cell ALL in CR1 benefit from HSCT (66).…”

Section: The Beijing Protocolmentioning

confidence: 99%

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Kleinschmidt

Yanir

et al. 2021

Front. Pediatr.

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Allogeneic haematopoietic stem cell transplantation (HSCT) represents a potentially curative option for children with high-risk or refractory/relapsed leukaemias. Traditional donor hierarchy favours a human leukocyte antigen (HLA)-matched sibling donor (MSD) over an HLA-matched unrelated donor (MUD), followed by alternative donors such as haploidentical donors or unrelated cord blood. However, haploidentical HSCT (hHSCT) may be entailed with significant advantages: besides a potentially increased graft-vs.-leukaemia effect, the immediate availability of a relative as well as the possibility of a second donation for additional cellular therapies may impact on outcome. The key question in hHSCT is how, and how deeply, to deplete donor T-cells. More T cells in the graft confer faster immune reconstitution with consecutively lower infection rates, however, greater numbers of T-cells might be associated with higher rates of graft-vs.-host disease (GvHD). Two different methods for reduction of alloreactivity have been established: in vivo T-cell suppression and ex vivo T-cell depletion (TCD). Ex vivo TCD of the graft uses either positive selection or negative depletion of graft cells before infusion. In contrast, T-cell-repleted grafts consisting of non-manipulated bone marrow or peripheral blood grafts require intense in vivo GvHD prophylaxis. There are two major T-cell replete protocols: one is based on post-transplantation cyclophosphamide (PTCy), while the other is based on anti-thymocyte globulin (ATG; Beijing protocol). Published data do not show an unequivocal benefit for one of these three platforms in terms of overall survival, non-relapse mortality or disease recurrence. In this review, we discuss the pros and cons of these three different approaches to hHSCT with an emphasis on the significance of the existing data for children with acute lymphoblastic leukaemia.

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Section: The Beijing Protocolmentioning

confidence: 99%

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Kleinschmidt

Yanir

et al. 2021

Front. Pediatr.

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“…34 Additionally, three studies demonstrated a correlation between the reemerging of MRD during intensification treatment in patients in CR and the occurrence of relapse. [35][36][37] In conclusion, the highly selected small group of HR patients have a relatively high survival rate of 79% with HR blocks (for some patients followed by SCT). Survival seems favorable compared with other studies reported in literature.…”

Section: Discussionmentioning

confidence: 85%

“…A study of 110 HR patients with a median of five MRD measurements after day 78, showed significant higher occurrence of relapse in patients with high MRD levels at one of more time points compared with patients with low or without quantifiable MRD levels 34 . Additionally, three studies demonstrated a correlation between the reemerging of MRD during intensification treatment in patients in CR and the occurrence of relapse 35–37 …”

Section: Discussionmentioning

confidence: 99%

Efficacy and toxicity of high‐risk therapy of the Dutch Childhood Oncology Group in childhood acute lymphoblastic leukemia

Binsbergen

Haas

Velden

et al. 2021

Pediatric Blood & Cancer

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Background: Children with acute lymphoblastic leukemia (ALL) and high-risk (HR) features have a poor outcome and are treated with HR blocks, often followed by allogenic stem cell transplantation (SCT).Procedure: This article analyses the outcomes of children treated with HR blocks between 2004 and 2017 according to DCOG ALL10/11 protocols. 1297 patients with newly diagnosed ALL were consecutively enrolled, of which 107 met the HR criteria (no complete remission; minimal residual disease (MRD) > 10 -3 after consolidation; "MLL-AF4" translocation and in ALL-10 also poor prednisone response). Patients were treated with one induction and consolidation course followed by three HR chemotherapy blocks, after which they received either SCT or further chemotherapy. MRD levels were measured at end of induction, consolidation, and after each HR block.Results: At five years, the event-free survival was 72.8% (95% CI, 64.6-82.0), and the cumulative incidence of relapse was 13.0% (95% CI, 6.3-19.8). Patients with only negative or low-positive MRD levels during HR blocks had a significantly lower five-year cumulative incidence of relapse (CIR) of 2.2% (95% CI, 0-6.6) compared with patients with one or more high-positive MRD levels (CIR 15.4%; 95% CI, 3.9-26.9). During the entire treatment protocol, 11.2% of patients died due to toxicity. Conclusions:The high survival with HR blocks seems favorable compared with other studies. However, the limit of treatment intensification might have been reached as the number of patients dying from leukemia relapse is about equal as the number of patients dying from toxicity. Patients with negative or low MRD levels during HR blocks have lower relapse rates.

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“…The entire treatment cycle consisted of induction therapy, consolidation therapy, reinduction therapy interspersed with consolidation therapy, and maintenance therapy. The details of the protocol are presented in our previous reports ( 8 , 10 ).…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of Wilms’ tumor gene 1 expression in children with B-cell precursor acute lymphoblastic leukemia

Xue,

Wang,

Zhang

et al. 2024

Front. Oncol.

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IntroductionThe prognostic role of Wilms’ tumor 1 (WT1) gene expression at diagnosis in children with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is still controversial.MethodsWe detected the WT1 transcript levels of 533 de novo pediatric BCP-ALL patients using TaqMan-based real-time quantitative PCR and analyzed their clinical features.ResultsThe WT1 transcript levels differed among the distinct molecularly defined groups, with the highest levels in the KMT2A rearrangements (KMT2A-r) group. According to the results of the X-tile software, all patients were divided into two groups: WT1/ABL ≥ 0.24% (group A) and <0.24% (group B). The proportions of patients whose age was ≥10 years old, with immunophenotype of Pro-B, belonging in high-risk group, or with minimal residual disease (MRD) ≥ 0.01% at week 12 were significantly higher in group A than in group B. In the B-other group, WT1 overexpression was an independent risk factor of overall survival (OS) rate (P = 0.042), and higher MRD ≥ 0.01% at week 12 was associated with lower OS rate (P<0.001) and event-free survival rate (P<0.001). Moreover, the subgroup analysis revealed that, in patients with initial WBC<50 × 109/L or MRD<0.1% at day 33 or MRD<0.01% at week 12 or in the standard-risk group, WT1 overexpression led to a poorer outcome in comparison with those with WT1 downexpression (P<0.05).DiscussionTherefore, pediatric BCP-ALL with WT1 overexpression had unique clinico-pathological characteristics and poor treatment response. In B-other patients, WT1 overexpression at diagnosis predicted an inferior prognosis. The WT1 gene may serve as a biomarker for monitoring residual disease in the B-other population, especially in children in the standard-risk group.

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Re-Emergence of Minimal Residual Disease Detected by Flow Cytometry Predicts an Adverse Outcome in Pediatric Acute Lymphoblastic Leukemia

Cited by 5 publications

References 24 publications

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Efficacy and toxicity of high‐risk therapy of the Dutch Childhood Oncology Group in childhood acute lymphoblastic leukemia

Prognostic significance of Wilms’ tumor gene 1 expression in children with B-cell precursor acute lymphoblastic leukemia

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