Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Purpose ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. Materials and Methods Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities. Results The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative- polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%. Conclusion ETV6/RUNX1 (+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end of remission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.
Abstract
Purpose ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. Materials and Methods Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities. Results The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative- polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%. Conclusion ETV6/RUNX1 (+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end of remission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.
참고문헌 (22)
- Shurtleff SA, "TEL", AML1 fusion resulting from a cryptic t(12;21)is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis, 1995, pp.9, 1985~1989
- Loh ML, "Prospective analysis of TEL", AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01, 2006, pp.107, 4508~4513
- Forestier E, "Outcome of ETV6", RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol : frequent late relapses but good overall survival, 2008, pp.140, 665~672
- Rubnitz JE, "Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia : a Children's Oncology Group study", J Clin Oncol, 26, pp.2186~2191 (2008)
- Bhojwani D, "ETV6-RUNX1-positive childhood acute lymphoblastic leukemia : improved outcome with contemporary therapy", Leukemia, 26, pp.265~270 (2012)
- Raynaud SD, "Cytogenetic abnormalities associated with the t(12;21) : a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia", Leukemia, 13, pp.1325~1330 (1999)
- Attarbaschi A, "Incidence and relevance of secondary chromosome abnormalities in childhood TEL", AML1+ acute lymphoblastic leukemia : an interphase FISH analysis, 2004, pp.18, 1611~1616
- Stams WA, "Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALLtreated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome", Leukemia, 20, pp.410~416 (2006)
- Pais AP, "RUNX1 aberrations in ETV6", RUNX1-positive and ETV6, Pediatr Hematol Oncol, pp.2008, 25[DOI]
- Attarbaschi A, "Deletion of 11q23 is a highly specific nonrandom secondary genetic abnormality of ETV6", RUNX1-rearranged childhood acute lymphoblastic leukemia, 2007, pp.21, 584~586
- Amare Kadam PS, "Coexistence of ETV6", RUNX1 and MLL aberrations in B-cell precursor acute lymphoblastic leukemia discloses a small subclass of BCP-ALL, 2008, pp.182, 27~32
- Papadhimitriou SI, "p16 inactivation associated with aggressive clinical course and fatal outcome in TEL", AML1-positive acute lymphoblastic leukemia, 2005, pp.27, 675~677
- Borst L, "Genome-wide analysis of cytogenetic aberrations in ETV6", RUNX1-positive childhood acute lymphoblastic leukaemia, 2012, pp.157, 476~482
- Lilljebjorn H, "Whole-exome sequencing of pediatric acute lymphoblastic leukemia", Leukemia, 26, pp.1602~1607 (2012)
- 김혜진, "Utility of a multiplex reverse transcriptasepolymerase chain reaction assay (HemaVision) in the evaluation of genetic abnormalities in Korean children with acute leukemia: a single institution study", Korean Journal of Pediatrics, 56(6), pp.247~253 (2013), 대한소아과학회
- Kyong-Won Bang, "Evaluation of changes in random blood glucose and body mass index during and after completion of chemotherapy in children with acute lymphoblastic leukemia", Korean Journal of Pediatrics, 55(4), pp.121~127 (2012), 대한소아과학회
- Madzo J, "Slower molecular response to treatment predicts poor outcome in patients with TEL", AML1 positive acute lymphoblastic leukemia : prospective real-time quantitative reverse transcriptase-polymerase chain reaction study, 2003, pp.97, 105~113
- Smith M, "Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia", J Clin Oncol, 14, pp.18~24 (1996)
- Byrd JC, "Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia : results from Cancer and Leukemia Group B(CALGB 8461)", Blood, 100, pp.4325~4336 (2002)
- Gandemer V, "Excellent prognosis of late relapses of ETV6", RUNX1-positive childhood acute lymphoblastic leukemia : lessons from the FRALLE 93 protocol, 2012, pp.97, 1743~1750
- Drunat S, "Quantification of TEL-AML1 transcript for minimal residual disease assessment in childhood acute lymphoblastic leukaemia", Br J Haematol, 114, pp.281~289 (2001)
- de Haas V, "The TEL-AML1 real-time quantitative polymerase chain reaction(PCR)might replace the antigen receptor-based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia", Br J Haematol, 116, pp.87~93 (2002)