Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia

被引：14

作者：

Kuwatsuka, Yachiyo ^{[1
]}

Tomizawa, Daisuke ^{[2
]}

Kihara, Rika ^{[3
]}

Nagata, Yasunobu ^{[4
]}

Shiba, Norio ^{[5
]}

Iijima-Yamashita, Yuka ^{[6
]}

Shimada, Akira ^{[7
]}

Deguchi, Takao ^{[8
]}

Miyachi, Hayato ^{[9
]}

Tawa, Akio ^{[10
]}

Taga, Takashi ^{[11
]}

Kinoshita, Akitoshi ^{[12
]}

Nakayama, Hideki ^{[13
]}

Kiyokawa, Nobutaka ^{[14
]}

Saito, Akiko Moriya ^{[6
]}

Koh, Katsuyoshi ^{[15
]}

Goto, Hiroaki ^{[16
]}

Kosaka, Yoshiyuki ^{[17
]}

Asou, Norio ^{[18
]}

Ohtake, Shigeki ^{[19
]}

Miyawaki, Shuichi ^{[20
]}

Miyazaki, Yasushi ^{[21
]}

Sakura, Toru ^{[22
]}

Ozawa, Yukiyasu ^{[23
]}

Usui, Noriko ^{[24
]}

Kanamori, Heiwa ^{[25
]}

Ito, Yoshikazu ^{[26
]}

Imai, Kiyotoshi ^{[27
]}

Suehiro, Youko ^{[28
]}

Kobayashi, Shinichi ^{[29
]}

Kitamura, Kunio

Sakaida, Emiko ^{[30
,31
]}

Ogawa, Seishi ^{[32
,33
]}

Naoe, Tomoki ^{[3
,34
]}

Hayashi, Yasuhide ^{[35
]}

Horibe, Keizo

Manabe, Atsushi ^{[36
]}

Mizutani, Shuki ^{[37
]}

Adachi, Souichi ^{[38
]}

Kiyoi, Hitoshi ^{[3
]}

机构：

[1] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan

[2] Natl Ctr Child Hlth & Dev, Childrens Canc Ctr, Div Leukemia & Lymphoma, Tokyo, Japan

[3] Nagoya Univ, Dept Hematol & Oncol, Grad Sch Med, Nagoya, Aichi, Japan

[4] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA

[5] Yokohama City Univ Med, Grad Sch Med, Dept Pediat, Yokohama, Kanagawa, Japan

[6] Natl Hosp Org, Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan

[7] Okayama Univ Hosp, Dept Pediat, Okayama, Japan

[8] Mie Univ, Grad Sch Med, Dept Pediat, Tsu, Mie, Japan

[9] Tokai Univ, Sch Med, Dept Lab Med, Isehara, Kanagawa, Japan

[10] Osaka Natl Hosp, Natl Hosp Org, Dept Pediat, Osaka, Japan

[11] Shiga Univ Med Sci, Dept Pediat, Otsu, Shiga, Japan

[12] St Marianna Univ, Sch Med, Dept Pediat, Kawasaki, Kanagawa, Japan

[13] Natl Hosp Org, Kyushu Canc Ctr, Dept Pediat, Fukuoka, Japan

[14] Natl Res Inst Child Hlth & Dev, Dept Pediat Hematol & Oncol Res, Tokyo, Japan

[15] Saitama Childrens Med Ctr, Dept Hematol Oncol, Saitama, Japan

[16] Kanagawa Childrens Med Ctr, Div Hematooncol & Regenerat Med, Yokohama, Kanagawa, Japan

[17] Hyogo Prefectural Kobe Childrens Hosp, Dept Hematol & Oncol, Kobe, Hyogo, Japan

[18] Saitama Med Univ, Int Med Ctr, Dept Hematol, Hidaka, Japan

[19] Kanazawa Univ, Kanazawa, Ishikawa, Japan

[20] Tokyo Metropolitan Otsuka Hosp, Div Hematol, Tokyo, Japan

[21] Nagasaki Univ, Grad Sch Biomed Sci, Atom Bomb Dis Inst, Dept Hematol, Nagasaki, Japan

[22] Saiseikai Maebashi Hosp, Leukemia Res Ctr, Maebashi, Gunma, Japan

[23] Japanese Red Cross Nagoya First Hosp, Dept Hematol, Nagoya, Aichi, Japan

[24] Jikei Univ, Sch Med, Dept Internal Med, Div Clin Oncol & Hematol, Tokyo, Japan

[25] Kanagawa Canc Ctr, Dept Hematol, Kanagawa, Japan

[26] Tokyo Med Univ, Dept Hematol, Tokyo, Japan

[27] Sapporo Hokuyu Hosp, Dept Hematol, Sapporo, Hokkaido, Japan

[28] Natl Hosp Org, Kyushu Canc Ctr, Dept Hematol, Fukuoka, Japan

[29] Natl Def Med Coll, Dept Internal Med, Div Hematol, Saitama, Japan

[30] Ichinomiya Municipal Hosp, Dept Hematol, Ichinomiya, Japan

[31] Chiba Univ Hosp, Dept Hematol, Chiba, Japan

[32] Univ Tokyo, Grad Sch Med, Canc Genom Project, Tokyo, Japan

[33] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan

[34] Natl Hosp Org, Nagoya Med Ctr, Nagoya, Aichi, Japan

[35] Gunma Childrens Med Ctr, Dept Hematol Oncol, Gunma, Japan

[36] St Lukes Int Hosp, Dept Pediat, Tokyo, Japan

[37] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Tokyo, Japan

[38] Kyoto Univ, Human Hlth Sci, Kyoto, Japan

来源：

INTERNATIONAL JOURNAL OF HEMATOLOGY | 2018年 / 107卷 / 02期

关键词：

AML; AYA; Genetic mutation; Prognosis; CELL TRANSPLANTATION; CHILDREN; OUTCOMES; IMPACT; AML; AGE; DIAGNOSIS; THERAPY; TRIALS;

D O I：

10.1007/s12185-017-2340-z

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

c Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in adolescent and young adults (AYAs) are known to differ in younger children and older adults. To clarify the impact of genetic mutations on clinical outcomes of AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies. AYAs aged 15-39 years (n = 103) were included. FLT3-ITD, KIT, CEBPA, NRAS, KRAS, WT1, MLL-PTD, and NPM1 mutations were analyzed. Overall survival (OS) of the AYAs was 61% and event-free survival was 38% at 3 years. FLT3-ITD (HR 2.10; 95% CI 1.07-4.12; p = 0.031) and NPM1 (HR 0.24; 95% CI 0.06-1.00; p = 0.050) mutations were associated with risk of overall mortality in multivariate analysis. OS was significantly different according to FLT3-ITD and NPM1 mutation status (p = 0.03). Survival was 100% with NPM1 mutations in the absence of FLT3-ITD and 35% (95% CI 14-57%) with FLT3-ITD in the absence of NPM1 mutations. The OS of AYAs, children (n = 413) and older adults (n = 124) of the AML-05 and AML201 participants were significantly different (p < 0.0001). This is the first report to combine clinical and genetic data of AYA AML from the major Japanese pediatric and adult study groups.

引用

页码：201 / 210

页数：10

共 31 条

[1] Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia [J].

Balgobind, Brian V. ;

Hollink, Iris H. I. M. ;

Arentsen-Peters, Susan T. C. J. M. ;

Zimmermann, Martin ;

Harbott, Jochen ;

Beverloo, H. Berna ;

von Bergh, Anne R. M. ;

Cloos, Jacqueline ;

Kaspers, Gertjan J. L. ;

de Haas, Valerie ;

Zemanova, Zuzana ;

Stary, Jan ;

Cayuela, Jean-Michel ;

Baruchel, Andre ;

Creutzig, Ursula ;

Reinhardt, Dirk ;

Pieters, Rob ;

Zwaan, C. Michel ;

van den Heuvel-Eibrink, Marry M. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (10) :1478-1487

[2] The incidence and clinical significance of nucleophosmin mutations in childhood AML [J].

Brown, Patrick ;

McIntyre, Emily ;

Rau, Rachel ;

Meshinchi, Soheil ;

Lacayo, Norman ;

Dahl, Gary ;

Alonzo, Todd A. ;

Chang, Myron ;

Arceci, Robert J. ;

Small, Donald .

BLOOD, 2007, 110 (03) :979-985

[3] Similar outcomes between adolescent/young adults and children with AML following allogeneic hematopoietic cell transplantation [J].

Burke, M. J. ;

Gossai, N. ;

Cao, Q. ;

MacMillan, M. L. ;

Warlick, E. ;

Verneris, M. R. .

BONE MARROW TRANSPLANTATION, 2014, 49 (02) :174-178

[4] Differences in Outcomes of Newly Diagnosed Acute Myeloid Leukemia for Adolescent/Young Adult and Younger Patients A Report from the Children's Oncology Group [J].

Canner, Jason ;

Alonzo, Todd A. ;

Franklin, Janet ;

Freyer, David R. ;

Gamis, Alan ;

Gerbing, Robert B. ;

Lange, Beverly J. ;

Meshinchi, Soheil ;

Woods, William G. ;

Perentesis, John ;

Horan, John .

CANCER, 2013, 119 (23) :4162-4169

[5]

COX DR, 1972, J R STAT SOC B, V34, P187

[6] Significance of age in acute myeloid leukemia patients younger than 30 years [J].

Creutzig, Ursula ;

Buechner, Thomas ;

Sauerland, Maria C. ;

Zimmermann, Martin ;

Reinhardt, Dirk ;

Doehner, Hartmut ;

Schlenk, Richard F. .

CANCER, 2008, 112 (03) :562-571

[7] Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet [J].

Doehner, Hartmut ;

Estey, Elihu H. ;

Amadori, Sergio ;

Appelbaum, Frederick R. ;

Buechner, Thomas ;

Burnett, Alan K. ;

Dombret, Herve ;

Fenaux, Pierre ;

Grimwade, David ;

Larson, Richard A. ;

Lo-Coco, Francesco ;

Naoe, Tomoki ;

Niederwieser, Dietger ;

Ossenkoppele, Gert J. ;

Sanz, Miguel A. ;

Sierra, Jorge ;

Tallman, Martin S. ;

Loewenberg, Bob ;

Bloomfield, Clara D. .

BLOOD, 2010, 115 (03) :453-474

[8] Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials [J].

Grimwade, David ;

Hills, Robert K. ;

Moorman, Anthony V. ;

Walker, Helen ;

Chatters, Stephen ;

Goldstone, Anthony H. ;

Wheatley, Keith ;

Harrison, Christine J. ;

Burnett, Alan K. .

BLOOD, 2010, 116 (03) :354-365

[9] Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML [J].

Hollink, I. H. I. M. ;

Zwaan, C. M. ;

Zimmermann, M. ;

Arentsen-Peters, T. C. J. M. ;

Pieters, R. ;

Cloos, J. ;

Kaspers, G. J. L. ;

de Graaf, S. S. N. ;

Harbott, J. ;

Creutzig, U. ;

Reinhardt, D. ;

van den Heuvel-Eibrink, M. M. ;

Thiede, C. .

LEUKEMIA, 2009, 23 (02) :262-270

[10] Investigation of the freely available easy-to-use software 'EZR' for medical statistics [J].

Kanda, Y. .

BONE MARROW TRANSPLANTATION, 2013, 48 (03) :452-458

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