International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

被引：76

作者：

Hrusak, Ondrej ^{[1
,2
]}

de Haas, Valerie ^{[3
,4
]}

Stancikova, Jitka ^{[1
,2
]}

Vakrmanova, Barbora ^{[1
,2
]}

Janotova, Iveta ^{[2
]}

Mejstrikova, Ester ^{[1
,2
]}

Capek, Vaclav ^{[5
]}

Trka, Jan ^{[1
,2
]}

Zaliova, Marketa ^{[1
,2
]}

Luks, Ales ^{[2
]}

Bleckmann, Kirsten ^{[6
,7
]}

Moericke, Anja ^{[6
,7
]}

Irving, Julie ^{[8
]}

Konatkowska, Benigna ^{[9
]}

Alexander, Thomas B. ^{[10
]}

Inaba, Hiroto ^{[10
]}

Schmiegelow, Kjeld ^{[11
,12
]}

Stokley, Simone ^{[13
]}

Zemanova, Zuzana ^{[14
,15
]}

Moorman, Anthony V. ^{[8
]}

Rossi, Jorge Gabriel ^{[16
]}

Felice, Maria Sara ^{[17
]}

Dalla-Pozza, Luciano ^{[18
]}

Morales, Jessa ^{[18
]}

Dworzak, Michael ^{[19
,20
]}

Buldini, Barbara ^{[21
]}

Basso, Giuseppe ^{[21
]}

Campbell, Myriam ^{[22
,23
]}

Cabrera, Maria Elena ^{[22
,23
]}

Marinov, Neda ^{[22
,23
]}

Elitzur, Sarah ^{[24
]}

Izraeli, Shai ^{[25
]}

Luria, Drorit ^{[24
]}

Feuerstein, Tamar ^{[24
]}

Kolenova, Alexandra ^{[26
]}

Svec, Peter ^{[26
]}

Kreminska, Olena ^{[27
]}

Rabin, Karen R. ^{[28
]}

Polychronopoulou, Sophia ^{[29
]}

da Costa, Elaine ^{[30
]}

Marquart, Hanne Vibeke ^{[12
]}

Kattamis, Antonis ^{[31
]}

Ratei, Richard ^{[32
]}

Reinhardt, Dirk ^{[33
]}

Choi, John K. ^{[34
]}

Schrappe, Martin ^{[6
,7
]}

Stary, Jan ^{[2
]}

机构：

[1] Childhood Leukemia Invest Prague, Prague, Czech Republic

[2] Charles Univ Prague, Dept Pediat Hematol Oncol, Fac Med 2, Hosp Motol, Prague, Czech Republic

[3] Dutch Childhood Oncol Grp, The Hague, Netherlands

[4] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[5] Charles Univ Prague, Fac Med 2, Bioinformat Ctr, Prague, Czech Republic

[6] Christian Albrechts Univ Kiel, Univ Med Ctr, Kiel, Germany

[7] Univ Med Ctr Schleswig Holstein, Dept Pediat, Campus Kiel, Kiel, Germany

[8] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England

[9] Univ Med Sci, Dept Pediat Hematol Oncol & Transplantol, Poznan, Poland

[10] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA

[11] Copenhagen Univ Hosp, Rigshosp, Nord Soc Pediat Hematol & Oncol, Dept Pediat & Adolescent Med,Juliane Marie Ctr, Copenhagen, Denmark

[12] Univ Copenhagen, Fac Med, Inst Med, Copenhagen, Denmark

[13] Nottingham Univ Hosp NHS Trust, Nottingham, England

[14] Charles Univ Prague, Gen Univ Hosp, Inst Med Biochem & Lab Diagnost, Ctr Oncocytogenet, Prague, Czech Republic

[15] Charles Univ Prague, Fac Med 1, Prague, Czech Republic

[16] Hosp Nacl Pediat Prof Dr JP Garrahan, Immunol & Rheumatol, Buenos Aires, DF, Argentina

[17] Hosp Nacl Pediat Prof Dr JP Garrahan, Hematol & Oncol, Buenos Aires, DF, Argentina

[18] Sydney Childrens Hosp Network, Westmead, NSW, Australia

[19] Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat, Vienna, Austria

[20] Childrens Canc Res Inst, Vienna, Austria

[21] Univ Padua, Dept Womans & Childs Hlth, Lab Pediat Oncohematol, Padua, Italy

[22] Univ Chile, Hosp Roberto del Rio, Chilean Natl Pediat Oncol Grp, Natl Program Antineoplast Drugs Children PINDA, Santiago, Chile

[23] Univ Chile, Hosp Salvador, Santiago, Chile

[24] Schneider Childrens Med Ctr, Pediat Hematol Oncol, Petah Tiqwa, Israel

[25] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[26] Comenius Univ Childrens Hosp, Bratislava, Slovakia

[27] Natl Childrens Specialized Hosp OHMATDYT, Ctr Childrens Oncohematol & BMT, Kiev, Ukraine

[28] Baylor Coll Med, Pediat Hematol Oncol, Houston, TX 77030 USA

[29] Aghia Sophia Childrens Hosp, Dept Pediat Hematol Oncol, Athens, Greece

[30] Univ Fed Rio de Janeiro, Fac Med, Pediat Dept, Rio De Janeiro, Brazil

[31] Univ Athens, Dept Pediat 1, Athens, Greece

[32] Helios Klinikum Berlin Buch, Berlin, Germany

[33] Univ Childrens Hosp Essen, Pediat Hematol & Oncol, Essen, Germany

[34] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA

来源：

BLOOD | 2018年 / 132卷 / 03期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; PHENOTYPE ACUTE-LEUKEMIA; AIEOP-BFM; B-ALL; CHILDREN; CLASSIFICATION; MYELOPEROXIDASE; EXPRESSION; PROGNOSIS; DIAGNOSIS;

D O I：

10.1182/blood-2017-12-821363

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Munster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)type primary therapy (80% +/- 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% +/- 7.2% and 50% +/- 12%, respectively). When ALL-or AML-specific gene fusions were excluded, 5-year EFS of CD19(+) leukemia was 83% +/- 5.3% on ALL-type primary treatment compared with 0% +/- 0% and 28% +/- 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19(+) ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19(-) and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with >= 5% blasts after remission induction. The results provide a basis for a prospective trial.

引用

页码：264 / 276

页数：13

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