Results of CoALL 07-03 study childhood ALL based on combined risk assessment by in vivo and in vitro pharmacosensitivity

Schramm, Franziska; Stadt, Udo zur; Zimmermann, Martin; Jorch, Norbert; Pekrun, Arnulf; Imschweiler, Thomas; Christiansen, Holger; Faber, Jörg; Schmid, Irene; Feuchtinger, Tobias; Beron, G.; Boer, Monique L. Den; Pieters, Rob; Horstmann, Martin; Janka‐Schaub, Gritta; Escherich, Gabriele

doi:10.1182/bloodadvances.2019000576

Cited by 21 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Greater prognostic heterogeneity of ETV6-RUNX1 (+) ALL patients may be the key factor for patients with high hyperdiploidy having significantly better EFS than those with ETV6-RUNX1 fusion in our study group. Overall, our results underscore the disparate outcome for the two canonical good prognosis genetic abnormalities of Pre-B ALL, and lower survival of our ETV6-RUNX1 (+) ALL patients (10-year EFS of 79.5±4.4%) compared to the excellent survival rates reported in past studies [ 2 , 8 , 9 ].…”

Section: Discussionsupporting

confidence: 58%

“…Although one past nationwide study showed a significantly higher relapse-free survival for girls compared with boys [ 15 ], recent studies have shown comparable outcome according to patient sex [ 2 , 9 , 10 ]. In our study, boys had lower 10-year EFS compared with girls, and patient sex proved to be a significant prognostic factor in multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Recent multi-center and multi-national cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) rates of > 80% and overall survival (OS) rates of ≥ 90% [1][2][3]. Regarding the overall treatment strategy for pediatric ALL, the addition of an intensification or reinduction phase for all patients regardless of risk group contributed to better outcome [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia

et al. 2021

View full text Add to dashboard Cite

Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell (Pre-B) ALL (n=405) diagnosed during a ten year period (2005-2015) at our institution. Materials and Methods All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission. Results The 10-year EFS and overall survival (OS) was 76.3±2.3% and 85.1±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8±2.2%, 3.7±1.1% and 2.5±0.9% respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2±3.0% vs. 79.5±4.4%, p=0.033). For the overall cohort, male gender, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study. Conclusion Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had CANCER RESEARCH AND TREATMENT (CRT) 3 Korean Cancer Association This article is protected by copyright. All rights reserved. significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

show abstract

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Nevertheless, Schramm et al recently demonstrated a lack of correlation between in vitro and in vivo drug response, as well as a lower predictive value of in vitro drug testing, reflecting an intrinsic limitation of this methodology that prevents its use for treatment stratification in future trials. Here, a simple fast in vitro model was prospectively applied for response prediction and treatment stratification accordingly using a 2D monoculture of patient samples and the methyl-thiazoltetrazolium viability assay [6]. The most widely used preclinical in vivo models for hematological malignancies are human tumor xenografts in immunodeficient mice [7].…”

Section: Introductionmentioning

confidence: 99%

Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Gauert

Olk

Pimentel-Gutiérrez

et al. 2020

Cancers

View full text Add to dashboard Cite

Only half of patients with relapsed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) currently survive with standard treatment protocols. Predicting individual patient responses to defined drugs prior to application would help therapy stratification and could improve survival. With the purpose to aid personalized targeted treatment approaches, we developed a human–zebrafish xenograft (ALL-ZeFiX) assay to predict drug response in a patient in 5 days. Leukemia blast cells were pericardially engrafted into transiently immunosuppressed Danio rerio embryos, and engrafted embryos treated for the test case, venetoclax, before single-cell dissolution for quantitative whole blast cell analysis. Bone marrow blasts from patients with newly diagnosed or relapsed BCP-ALL were successfully expanded in 60% of transplants in immunosuppressed zebrafish embryos. The response of BCP-ALL cell lines to venetoclax in ALL-ZeFiX assays mirrored responses in 2D cultures. Venetoclax produced varied responses in patient-derived BCP-ALL grafts, including two results mirroring treatment responses in two refractory BCP-ALL patients treated with venetoclax. Here we demonstrate proof-of-concept for our 5-day ALL-ZeFiX assay with primary patient blasts and the test case, venetoclax, which after expanded testing for further targeted drugs could support personalized treatment decisions within the clinical time window for decision-making.

show abstract

“…Advances in childhood ALL treatment Результаты лечения острого лимфобластного лейкоза по современным протоколам терапии[10,26,[29][30][31][32][33] Treatment results of acute lymphoblastic leukemia according to modern therapy protocols[10,26,[29][30][31][32][33] …”

unclassified

Pediatric acute lymphoblastic leukemia treatment protocols improvement: emphasis on minimal residual disease

Шервашидзе

Валиев

2020

Onkogematologiâ

View full text Add to dashboard Cite

Treatment of acute lymphoblastic leukemia (ALL) in children during the last 50 years has changed significantly, which has increased the survival of patients from 10–15 % in the early 60s to 80–85 % by the mid-2000s. Such results have been achieved through the development of new polychemotherapy regimens, the introduction of neuroleukemia prophylaxis, the strengthening of standard chemotherapy by increasing the dose and / or frequency of chemotherapeutic drugs administration, and the definition of criteria for patient stratification into prognostic risks groups and the development of principles of risk-adopted therapy.However, inspite of the overall success of pediatric acute lymphoblastic leukemia therapy, some variants of acute lymphoblastic leukemia associated with poor prognosis, especially acute lymphoblastic leukemia with BCR-ABL1 and MLL rearrangements. Besides the prolonged persistence of minimal residual disease is also an unfavorable prognostic factor requiring therapy intensification.In the current issue we present the main steps in the evolution of programmed chemotherapy of children with acute lymphoblastic leukemia. Great attention was paid for modern risk-stratifying criteria with an emphasis on minimal residual disease.

show abstract

Results of CoALL 07-03 study childhood ALL based on combined risk assessment by in vivo and in vitro pharmacosensitivity

Abstract: Key Points Report of the long-term outcome of children with acute lymphoblastic leukemia upon risk-adapted therapy accrued in trial CoALL 07-03. Lack of correlation between in vitro and in vivo drug response as well as a lower predictive value of in vitro drug testing.

Cited by 21 publications

References 31 publications

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia

Fast, In Vivo Model for Drug-Response Prediction in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Pediatric acute lymphoblastic leukemia treatment protocols improvement: emphasis on minimal residual disease

Contact Info

Product

Resources

About