Long-term results of treatment of childhood acute lymphoblastic leukemia in the Czech Republic

Starý, Jan; Jabali, Yahia; Trka, Jan; Hrušák, Ondřej; Gajdoš, Petr; Hrstková, Hana; Štěrba, Jaroslav; Blažek, Bohumír; Hak, Jiří; Procházková, D.; Černá, Zuzana; Smíšek, Petr; Sedláček, Petr; Vávra, V.; Mihál, Vladimı́r; Hrodek, O

doi:10.1038/leu.2009.255

Cited by 19 publications

(6 citation statements)

References 3 publications

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“…Although the use of intensive chemotherapy has enabled patients with T-cell ALL to fare as well as patients with B-cell precursor ALL in some studies, the outcomes are significantly worse for the patients with T-cell ALL in most treatment protocols [3][4][5][6][7][8][9][10][11][12][13][14][15]. Chromosomal alterations, including numbers and translocations, have helped to classify pediatric patients with B-cell precursor ALL and improve treatment outcomes in the past three decades [16].…”

Section: Introductionmentioning

confidence: 99%

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Yang

Hsiao

Chen

et al. 2011

Pediatric Blood & Cancer

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BackgroundThe absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T‐cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T‐cell ALL.ProcedureForty‐five children with T‐cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q‐PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q‐PCR was defined as a fold‐change <0.35.ResultsABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23–53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10–16.42).ConclusionsThe absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T‐cell ALL in Taiwan. Providing patients with T‐cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials. Pediatr Blood Cancer 2012; 58: 846–851. © 2011 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Yang

Hsiao

Chen

et al. 2011

Pediatric Blood & Cancer

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“…Here we demonstrate that our single-center results were steadily comparable to the nationwide data. [6,19] The mentioned outcomes surpassed international results of the ALL IC-BFM 2002 trial (5-year EFS 74%, OS 82%) [7] and were comparable with world's leading childhood leukemia trials -e.g. a 7-year EFS 80.4% and OS 91.8% for AIEOP-BFM ALL 2000; 5-year OS 90.4% for protocol of the Children's Oncology Group (COG).…”

Section: Discussionmentioning

confidence: 62%

“…Clinical data of the nationwide cohort have been published as a part of previous studies. [5][6][7] The median follow-up period of the study group was 16.3, 12.6 and 7.7 years for ALL-BFM 90, ALL-BFM 95 and ALL IC-BFM 2002, respectively.…”

Section: Methodsmentioning

confidence: 99%

Treatment and prognosis of childhood acute lymphoblastic leukemia on protocols ALL-BFM 90, 95 and ALL IC-BFM 2002: a retrospective single-center study from Olomouc, Czech Republic

Volejnikova¹,

Jarošová²,

Pospı́šilová³

et al. 2016

neo

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Great progress has been made in the diagnostics and treatment of childhood acute lymphoblastic leukemia (ALL) over the past decades. The vast majority of children are cured, however, there is need for further improvement, especially in specific patient subgroups. Our aim was to retrospectively evaluate disease characteristics and treatment outcomes of children with ALL enrolled in a single center into consecutive treatment protocols (ALL-BFM 90, ALL-BFM 95 and ALL IC-BFM 2002) between years 1990 and 2007 and comprehensively summarize diagnostic and therapeutic advances between protocols. In total, 97 patients aged 0 to 18 years were treated for ALL at University Hospital Olomouc in the Czech Republic and steadily high relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) were observed during the evaluated time period without significant difference between the protocols (RFS 80-86%, EFS 75-83% and OS 84-92%). In conclusion, our center has demonstrated survival rates comparable to leading international study groups for childhood ALL over a substantial period of time. This has been achieved namely due to advances in diagnostics, excellent collaboration on regional, national and international level, quality assurance and high overall standard of care. The acquired experience has been crucial for current participation in the best performing Berlin-Frankfurt-Münster (BFM)-based international trials for childhood ALL.

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“…The clinical workup was done on a real-time basis because of the need of urgent transfusion in some pediatric patients that would otherwise disable erythrocyte TPMT determination. In patients receiving thiopurines, toxicity was scored using standard measures [16] and standard reporting was performed as requested by cooperative group protocols [17,18]. We did not specifically address clinical toxicity within the phenotype/genotype interpretive categories (online suppl.…”

Section: Resultsmentioning

confidence: 99%

Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation

Demlová

Mrkvicova²,

Štěrba

et al. 2014

Oncology

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Objective: Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported. Patients and Methods: The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method. Results: Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT *1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wild-type and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient. Conclusion: Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism.

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Long-term results of treatment of childhood acute lymphoblastic leukemia in the Czech Republic

Cited by 19 publications

References 3 publications

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Treatment and prognosis of childhood acute lymphoblastic leukemia on protocols ALL-BFM 90, 95 and ALL IC-BFM 2002: a retrospective single-center study from Olomouc, Czech Republic

Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation

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