Early (Day 15 Post Diagnosis) Peripheral Blood Assessment of Measurable Residual Disease in Flow Cytometry is a Strong Predictor of Outcome in Childhood B‐Lineage Lymphoblastic Leukemia

Loosveld, Marie; Nivaggioni, Vanessa; Arnoux, Isabelle; Bernot, Denis; Gautier, Michel; Béné, Marie C.; Eveillard, Marion

doi:10.1002/cyto.b.21769

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…Supplementary Table S4 has also been evaluated in other studies. Among patients who received Berlin-Frankfurt-Münster (BFM) backbone treatment regimens, the day-8 MRD result in blood after 1 week of pre-phase prednisone therapy and intrathecal methotrexate had little prognostic impact (15)(16)(17). Among B-ALL patients treated in the COG P9900 protocols, however, a day-8 MRD≤0.01% in blood after 3-or 4-drug induction plus intrathecal therapy was associated with a better eventfree survival, while increasing levels of MRD at that time point were associated with a progressively worse outcome (18,19).…”

Section: Outcome Of T-all Subgroups Segregated By Expression Of Transmentioning

confidence: 99%

Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Jeha

Choi

Roberts

et al. 2021

Blood Cancer Discovery

109

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We evaluate clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)-directed therapy. Among the 16 B-ALL and 8 T-ALL subtypes identified by next generation sequencing, ETV6-RUNX1, highhyperdiploid and DUX4-rearranged B-ALL had the best five-year event-free survival rates (95% to 98.4%); TCF3-PBX1, PAX5alt, T-cell, ETP, iAMP21, and hypodiploid ALL intermediate rates (80.0% to 88.2%); and BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like and KMT2Arearranged ALL the worst rates (64.1% to 76.2%). All but three of the 142 patients with day-8 blood MRD <0.01% remained in remission. Among new subtypes, intensified therapy based on day-15 MRD≥1% improved outcome of DUX4-rearranged, BCR-ABL1-like, and ZNF384rearranged ALL, and achievement of day-42 MRD<0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged and ETV6-RUNX1-like ALL. Thus, new subtypes including DUX4rearranged, PAX5alt, BCR-ABL1-like, ETV6-RUNX1-like, MEF2D-rearranged and ZNF384rearranged ALL have important prognostic and therapeutic implications. SIGNIFICANCE:Genomic analyses and MRD should be used together for risk-directed treatment. Six recently described subtypes --DUX4-rearranged, PAX5alt, BCR-ABL1-like, ETV6-RUNX1-like, MEF2Drearranged, and ZNF384-rearranged ALL --had prognostic and therapeutic significance with contemporary risk-directed treatment.

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Section: Outcome Of T-all Subgroups Segregated By Expression Of Transmentioning

confidence: 99%

Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Jeha

Choi

Roberts

et al. 2021

Blood Cancer Discovery

109

View full text Add to dashboard Cite

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“…Flow cytometry (FCM)-MRD was analyzed according to previous literature from French multicenter study groups for pediatric and adult ALL [19][20][21] . MRD was analyzed at the central protocol laboratory-the hematology labs of Kingmed Diagnostics Coorperation by Kaluza software or Cellquest software.…”

Section: Minimal Residual Disease Evaluationmentioning

confidence: 99%

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol

Luo

et al. 2020

Preprint

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Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70%-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong(GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality(TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. Methods The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1,765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2 %) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day33 positive group (n=7) was 28.6%, while in the MRD Day33 negative group (n=67) was 7.5% (p=0.129).Conclusions The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

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“…Flow cytometry (FCM)-MRD was analyzed according to previous literature from French multicenter study groups for pediatric and adult ALL [19][20][21] . MRD was analyzed by Kaluza software or Cellquest software.…”

Section: Minimal Residual Disease Measurementmentioning

confidence: 99%

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol

Luo

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70%-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong(GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality(TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate weather the reduced intensity is effective and safe for children with ALL. Methods The clinical data was obtained from February 28, 2008 to June 30, 2016. A total of 1,765 childhood ALL cases from 9 medical centers were collected and data was retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). The dose of cyclophosphamide (CTX), Cytarabine (Ara-c) and 6-mercaptopurine (6-MP) during CAM induction for the SR group was half that of the BFM 2002 and was reduced to 2 weeks.Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2 %) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day33 positive group (n=7) was 28.6%, while in the MRD Day33 negative group (n=67) was 7.5% (p=0.129).Conclusions The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

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Early (Day 15 Post Diagnosis) Peripheral Blood Assessment of Measurable Residual Disease in Flow Cytometry is a Strong Predictor of Outcome in Childhood B‐Lineage Lymphoblastic Leukemia

Cited by 11 publications

References 34 publications

Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol

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