International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

Ondrej Hrusak; Valerie de Haas; Jitka Stancikova; Barbora Vakrmanova; Iveta Janotova; Ester Mejstrikova; Vaclav Capek; Jan Trka; Marketa Zaliova; Ales Luks; Kirsten Bleckmann; Anja Möricke; Julie Irving; Benigna Konatkowska; Thomas B Alexander; Hiroto Inaba; Kjeld Schmiegelow; Simone Stokley; Zuzana Zemanova; Anthony V Moorman; Jorge Gabriel Rossi; Maria Sara Felice; Luciano Dalla-Pozza; Jessa Morales; Michael Dworzak; Barbara Buldini; Giuseppe Basso; Myriam Campbell; Maria Elena Cabrera; Neda Marinov; Sarah Elitzur; Shai Izraeli; Drorit Luria; Tamar Feuerstein; Alexandra Kolenova; Peter Svec; Olena Kreminska; Karen R Rabin; Sophia Polychronopoulou; Elaine da Costa; Hanne Vibeke Marquart; Antonis Kattamis; Richard Ratei; Dirk Reinhardt; John K Choi; Martin Schrappe; Jan Stary

doi:10.1182/blood-2017-12-821363

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

Ondrej Hrusak, Valerie de Haas, Jitka Stancikova, Barbora Vakrmanova, Iveta Janotova, Ester Mejstrikova, Vaclav Capek, Jan Trka, Marketa Zaliova, Ales Luks, Kirsten Bleckmann, Anja Möricke, Julie Irving, Benigna Konatkowska, Thomas B Alexander, Hiroto Inaba, Kjeld Schmiegelow, Simone Stokley, Zuzana Zemanova, Anthony V MoormanJorge Gabriel Rossi, Maria Sara Felice, Luciano Dalla-Pozza, Jessa Morales, Michael Dworzak, Barbara Buldini, Giuseppe Basso, Myriam Campbell, Maria Elena Cabrera, Neda Marinov, Sarah Elitzur, Shai Izraeli, Drorit Luria, Tamar Feuerstein, Alexandra Kolenova, Peter Svec, Olena Kreminska, Karen R Rabin, Sophia Polychronopoulou, Elaine da Costa, Hanne Vibeke Marquart, Antonis Kattamis, Richard Ratei, Dirk Reinhardt, John K Choi, Martin Schrappe, Jan Stary

Department of Clinical Medicine

36 Citations (Scopus)

Abstract

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-Münster 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% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19¹ leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 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 CD19¹ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 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. (Blood.

Original language	English
Journal	Blood
Volume	132
Issue number	3
Pages (from-to)	264-276
Number of pages	13
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2017-12-821363
Publication status	Published - 19 Jul 2018

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Hrusak, O., de Haas, V., Stancikova, J., Vakrmanova, B., Janotova, I., Mejstrikova, E., Capek, V., Trka, J., Zaliova, M., Luks, A., Bleckmann, K., Möricke, A., Irving, J., Konatkowska, B., Alexander, T. B., Inaba, H., Schmiegelow, K., Stokley, S., Zemanova, Z., ... Stary, J. (2018). International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood, 132(3), 264-276. https://doi.org/10.1182/blood-2017-12-821363

Hrusak, O, de Haas, V, Stancikova, J, Vakrmanova, B, Janotova, I, Mejstrikova, E, Capek, V, Trka, J, Zaliova, M, Luks, A, Bleckmann, K, Möricke, A, Irving, J, Konatkowska, B, Alexander, TB, Inaba, H, Schmiegelow, K, Stokley, S, Zemanova, Z, Moorman, AV, Rossi, JG, Felice, MS, Dalla-Pozza, L, Morales, J, Dworzak, M, Buldini, B, Basso, G, Campbell, M, Cabrera, ME, Marinov, N, Elitzur, S, Izraeli, S, Luria, D, Feuerstein, T, Kolenova, A, Svec, P, Kreminska, O, Rabin, KR, Polychronopoulou, S, da Costa, E, Marquart, HV, Kattamis, A, Ratei, R, Reinhardt, D, Choi, JK, Schrappe, M & Stary, J 2018, 'International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia', Blood, vol. 132, no. 3, pp. 264-276. https://doi.org/10.1182/blood-2017-12-821363

@article{edde41be297546a48982e0266983bd2a,

title = "International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia",

abstract = "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-M{\"u}nster 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% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD191 leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 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 CD191 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 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. (Blood.",

author = "Ondrej Hrusak and {de Haas}, Valerie and Jitka Stancikova and Barbora Vakrmanova and Iveta Janotova and Ester Mejstrikova and Vaclav Capek and Jan Trka and Marketa Zaliova and Ales Luks and Kirsten Bleckmann and Anja M{\"o}ricke and Julie Irving and Benigna Konatkowska and Alexander, {Thomas B} and Hiroto Inaba and Kjeld Schmiegelow and Simone Stokley and Zuzana Zemanova and Moorman, {Anthony V} and Rossi, {Jorge Gabriel} and Felice, {Maria Sara} and Luciano Dalla-Pozza and Jessa Morales and Michael Dworzak and Barbara Buldini and Giuseppe Basso and Myriam Campbell and Cabrera, {Maria Elena} and Neda Marinov and Sarah Elitzur and Shai Izraeli and Drorit Luria and Tamar Feuerstein and Alexandra Kolenova and Peter Svec and Olena Kreminska and Rabin, {Karen R} and Sophia Polychronopoulou and {da Costa}, Elaine and Marquart, {Hanne Vibeke} and Antonis Kattamis and Richard Ratei and Dirk Reinhardt and Choi, {John K} and Martin Schrappe and Jan Stary",

note = "{\textcopyright} 2018 by The American Society of Hematology.",

year = "2018",

month = jul,

day = "19",

doi = "10.1182/blood-2017-12-821363",

language = "English",

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journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

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T1 - International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

AU - Hrusak, Ondrej

AU - de Haas, Valerie

AU - Stancikova, Jitka

AU - Vakrmanova, Barbora

AU - Janotova, Iveta

AU - Mejstrikova, Ester

AU - Capek, Vaclav

AU - Trka, Jan

AU - Zaliova, Marketa

AU - Luks, Ales

AU - Bleckmann, Kirsten

AU - Möricke, Anja

AU - Irving, Julie

AU - Konatkowska, Benigna

AU - Alexander, Thomas B

AU - Inaba, Hiroto

AU - Schmiegelow, Kjeld

AU - Stokley, Simone

AU - Zemanova, Zuzana

AU - Moorman, Anthony V

AU - Rossi, Jorge Gabriel

AU - Felice, Maria Sara

AU - Dalla-Pozza, Luciano

AU - Morales, Jessa

AU - Dworzak, Michael

AU - Buldini, Barbara

AU - Basso, Giuseppe

AU - Campbell, Myriam

AU - Cabrera, Maria Elena

AU - Marinov, Neda

AU - Elitzur, Sarah

AU - Izraeli, Shai

AU - Luria, Drorit

AU - Feuerstein, Tamar

AU - Kolenova, Alexandra

AU - Svec, Peter

AU - Kreminska, Olena

AU - Rabin, Karen R

AU - Polychronopoulou, Sophia

AU - da Costa, Elaine

AU - Marquart, Hanne Vibeke

AU - Kattamis, Antonis

AU - Ratei, Richard

AU - Reinhardt, Dirk

AU - Choi, John K

AU - Schrappe, Martin

AU - Stary, Jan

PY - 2018/7/19

Y1 - 2018/7/19

N2 - 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-Münster 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% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD191 leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 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 CD191 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 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. (Blood.

AB - 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-Münster 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% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD191 leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 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 CD191 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 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. (Blood.

U2 - 10.1182/blood-2017-12-821363

DO - 10.1182/blood-2017-12-821363

M3 - Journal article

C2 - 29720486

SN - 0006-4971

VL - 132

SP - 264

EP - 276

JO - Blood

JF - Blood

IS - 3

ER -

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

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