Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Munster Study Group

被引:29
作者
van Weelderen, Romy E. [1 ,2 ]
Klein, Kim [1 ,2 ,3 ]
Harrison, Christine J. [4 ]
Jiang, Yilin [1 ]
Abrahamsson, Jonas [5 ]
Arad-Cohen, Nira [6 ]
Bart-Delabesse, Emmanuelle [7 ]
Buldini, Barbara [8 ]
De Moerloose, Barbara [9 ]
Dworzak, Michael N. [10 ,11 ]
Elitzur, Sarah [12 ]
Fernandez Navarro, Jose M. [13 ]
Gerbing, Robert B. [14 ]
Goemans, Bianca F. [1 ]
de Groot-Kruseman, Hester A. [1 ,15 ]
Guest, Erin [16 ]
Ha, Shau-Yin [17 ]
Hasle, Henrik [18 ]
Kelaidi, Charikleia [19 ]
Lapillonne, Helene [20 ]
Leverger, Guy [20 ]
Locatelli, Franco [21 ]
Masetti, Riccardo [22 ]
Miyamura, Takako [23 ]
Noren-Nystrom, Ulrika [24 ]
Polychronopoulou, Sophia [19 ]
Rasche, Mareike [25 ]
Rubnitz, Jeffrey E. [26 ]
Stary, Jan [27 ,28 ]
Tierens, Anne [29 ]
Tomizawa, Daisuke [30 ]
Zwaan, C. Michel [1 ,31 ]
Kaspers, Gertjan J. L. [1 ,2 ]
机构
[1] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands
[2] Vrije Univ Amsterdam, Emma Childrens Hosp, Pediat Oncol, Amsterdam UMC, Amsterdam, Netherlands
[3] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Utrecht, Netherlands
[4] Newcastle Univ Ctr Canc, Leukemia Res Cytogenet Grp, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England
[5] Salgrenska Univ Hosp, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden
[6] Ruth Rappaport Childrens Hosp, Pediat Hemato Oncol Dept, Rambam Hlth Care Campus, Haifa, Israel
[7] IUC Toulouse Oncopole, Lab Hematol Secteur G enet Hemopathies, Toulouse, France
[8] Univ Padua, Oncol & Stem Cell Transplant Div, Maternal & Child Hlth Dept, Pediat Hematol, Padua, Italy
[9] Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Ghent, Belgium
[10] Med Univ Vienna, Dept Pediat, St Anna Childrens Hosp, Vienna, Austria
[11] St Anna Childrens Canc Res Inst, Vienna, Austria
[12] Schneider Childrens Med Ctr & Tel Aviv Univ, Dept Pediat Hematol & Oncol, Tel Aviv, Israel
[13] Hosp Univ Politecn La Fe, Pediat Oncohematol Unit, Valencia, Spain
[14] Childrens Oncol Grp, Dept Stat, Monrovia, CA USA
[15] Dutch Childhood Oncol Grp, DCOG, Utrecht, Netherlands
[16] Childrens Mercy Kansas City, Kansas City, MO USA
[17] Hong Kong Childrens Hosp, Dept Pediat & Adolescent Med, Kowloon, Hong Kong, Peoples R China
[18] Aarhus Univ Hosp, Pediat & Adolescent Med, Aarhus, Denmark
[19] Aghia Sophia Childrens Hosp, Dept Pediat Hematol & Oncol, Athens, Greece
[20] Hop Armand Trousseau, Pediat Hematol & Oncol Dept, Paris, France
[21] Cathol Univ Sacred Heart, Dept Pediat Hematol & Oncol & Cell & Gene Therapy, IRCCS Osped Pediatr Bambino GesU, Rome, Italy
[22] Univ Bologna, Pediat Oncol & Hematol, IRCCS Azienda Osped Univ Bologna, Bologna, Italy
[23] Osaka Univ, Dept Pediat, Grad Sch Med, Suita, Osaka, Japan
[24] Umea Univ, Dept Clin Sci, Pediat, Umea, Sweden
[25] Univ Hosp Essen, Dept Pediat Hematol & Oncol, Essen, Germany
[26] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN USA
[27] Charles Univ Prague, Univ Hosp Motol, Dept Pediat Hematol & Oncol, Prague, Czech Republic
[28] Charles Univ Prague, Fac Med 2, Prague, Czech Republic
[29] Toronto Gen Hosp, Univ Hlth Network, Dept Pathobiol & Lab Med, Toronto, ON, Canada
[30] Natl Ctr Child Hlth & Dev, Childrens Canc Ctr, Tokyo, Japan
[31] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol, Rotterdam, Netherlands
基金
美国国家卫生研究院;
关键词
AIEOP-AML; 2002/01; FLOW-CYTOMETRY; CHILDREN; CHEMOTHERAPY; ADOLESCENTS; TRIAL; TRANSPLANTATION; INDUCTION;
D O I
10.1200/JCO.22.02120
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSE A previous study by the International Berlin-Frankfurt-Munster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease. METHODS A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (>= 0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS). RESULTS The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS. CONCLUSION EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.
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收藏
页码:2963 / 2974
页数:13
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