Acute leukemia of ambiguous lineage (ALAL) is a rare entity within acute leukemias, which for several reasons may be considered borderline between the typical lymphoblastic (ALL) or myeloid (AML) acute leukemias. ALALs partially overlap with several other subsets of acute leukemia. Clinicians and scientists often discuss the definition and optimal treatment of ALAL and there is a clear need for guidance on ALAL treatment. The aim of studies described on this page is to improve our understanding of ALAL biology and to help find the best treatment for ALAL patients.
The following four different types of ALAL have been described:
Most of these leukemias fulfill one of the two international definitions, both of which principally rely on flow cytometry. An older definition by the European Group for Immunophenotyping of Leukemia (EGIL) uses a spectrum of antigens weighted by their presumed significance. A newer definition by World Health Organization (WHO) utilizes fewer antigens. In general, the prognosis of ALAL is slightly worse than that of the other acute leukemias on the same type of treatment.
Scoring points | B lineage | T lineage | My lineage |
---|---|---|---|
2 | (intra)CD79a, intraIgM, (intra)CD22 | (intra)CD3, TCRαβ, TCRγδ | intraMPO |
1 | CD19, CD10, CD20 | CD2, CD5, CD8, CD10 | CD13,CD33,CD65,CD117 |
0.5 | intraTdT, CD24 | intraTdT, CD7, CD1a | CD14,CD15, CD64 |
Lineage assignment | Criteria definition |
---|---|
Myeloid lineage |
intraMPO (flow cytometry, immunohistochemistry, or cytochemistry) or Monocytic differentiation (at least 2 of the following: nonspecific esterase cytochemistry, CD11c, CD14, CD64, lysozyme) |
T-lineage |
Strong† intraCD3 or Surface CD3 |
B-lineage |
Strong† CD19 with at least 1 of the following strongly expressed: CD79a, intraCD22, or CD10 or Weak CD19 with at least 2 of the following strongly expressed: CD79a, intraCD22, or CD10 |
ALAL cases are relatively rare, constituting 2-6% of acute leukemias. Therefore, many previous studies including those of the authors of this webpage were too small (usually below 50 of children or adults with ALAL) to make detailed analyses including survival analyses of ALAL subsets on different types of treatment.
Past: In 2012, a retrospective international study was launched within the iBFM Study Group aimed at collecting data on children with ALAL. The first cohort of patients was analyzed in a study called iBFM AMBI2012. Children were from several countries: Australia (single hospital), Austria, Brazil (single hospital), Czechia, Germany, Greece (single hospital), Israel, Italy, Netherlands, the NOPHO group (representing Denmark, Estonia, Finland, Norway, Sweden, Iceland and Lithuania), PINDA (Chile), Poland, SAHOP (Argentina), Slovakia, St. Jude Children's Research Hospital and Baylor College of Medicine (USA), Ukraine and the United Kingdom. By 2018, we managed to accumulate data on over 300 cases, making this network the largest in the field of ALAL. The main aim is to improve the outcome of children with ALAL, via exploring biologic features and clinical data.
Future: We are now starting a new prospective registry iBFM AMBI2018. Japan, Moscow, Spain, Switzerland, Hungary and partially China joined the project.
ALAL is a very diverse subset of acute leukemias. Just like any acute leukemia, ALAL is a serious disease that requires aggressive treatment. Currently, most children with acute leukemia are cured, provided they are being treated in experienced pediatric hematology/oncology centers.
The ALAL subtype of leukemia has a somewhat worse prognosis than that of non ALAL acute leukemia. However, the diversity of ALALs points to the fact that the prognosis of each individual patient depends largely on their laboratory findings. These findings include gene abnormalities and types of protein in the leukemia cells, underlying diseases, and, very importantly, response to the treatment given.
If you/your child with ALAL are being treated in an experienced hospital, most likely the physicians will do their best to select the best available treatment. While it is possible that the physician may contact us for a consult, it is entirely up to the physicians who are immediately in charge of the patient, whether they consult on their treatment decisions and with whom.
Chances are that your physician will ask you to participate in a study organized by our group. If you agree with such participation, your data will help you and other patients who are diagnosed with ALAL in the future. We, physicians and researchers involved in searching for the best treatment of ALAL, thank you for it!
ALAL exists also in adulthood. We focus on children up to 18 years of age. At the moment, we are not aware of any similar large study on adult ALALs. If one comes to light, we will place a link here.
As we said, international cooperation is necessary. We are now starting a new prospective registry iBFM AMBI2018. We would welcome any center which wants to join the registry. If you want to be part of the registry or need more information about what is required from centers, please contact ondrej.hrusak@lfmotol.cuni.cz.
From results from the retrospective study, iBFM AMBI2012, we created an algorithm for treatment of ALALs. In iBFM AMBI2018 we want to test this algorithm prospectively and compare results with the previous study. We hope to see an improvement in prognosis.
After we create you a user account, you can sign in here: https://ambistudy.lf2.cuni.cz. In the website you can register new patients, upload files with cytometry data and review all added data. You won′t be able to see patients′ data from other groups in the study.
When you register a patient to the online database, we will consider if they fulfill the criteria for joining the registry. Only patients of participating centers can be in the registry. However, non-participating patients are included even if they are diagnosed before or after the registry accrual is opened.
Coordinator | Ondřej Hrušák | ondrej.hrusak@lfmotol.cuni.cz | +420 22443 6477 |
---|---|---|---|
Coordinator, morphology | Valerie de Haas | v.dehaas@prinsesmaximacentrum.nl | +31 (70) 3674545 |
Genetic consulting | Markéta Žaliová | marketa.zaliova@lfmotol.cuni.cz | +420 22443 6580 |
Technical help | Barbora Vakrmanová | barbora.vakrmanova@lfmotol.cuni.cz | +420 22443 6477 |
Name |
Country |
|
---|---|---|
Luciano Dalla-Pozza | luciano.dallapozza@health.nsw.gov.au | Australia |
Karen Rabin | krrabin@txch.org | USA (Texas Children‘s Hospital) |
Hiroto Inaba | hiroto.inaba@stjude.org | USA (St. Jude Children´s Research Hospital) |
Elaine Sobral da Costa | elainesc@centroin.com.br | Brazil |
Sophia Polychronopoulou | s.polychronopoulou@paidon-agiasofia.gr | Greece |
Barbara Buldini | barbara.buldini@unipd.it | Italy |
Sarah Elitzur | sarhae@clalit.org.il | Israel |
Kjeld Schmiegelow | kjeld.schmiegelow@regionh.dk | Scandinavia (NOPHO) |
Anja Möricke | a.moericke@pediatrics.uni-kiel.de | Germany (Kiel) |
Dirk Reinhardt | dirk.reinhardt@uk-essen.de | Germany (Essen) |
Myriam Campbell | myriamcampbellb@gmail.com | Chile (PINDA) |
Olga Zając | olga_zajac@wp.pl | Poland |
Jorge Rossi | jrossi@garrahan.gov.ar | Argentina (SAHOP) |
Peter Švec | peter.svec@gmail.com | Slovakia |
Olena Kreminska | elena_kreminska@ukr.net | Ukraine |
Michael Dworzak | michael.dworzak@stanna.at | Austria |
Julie Irving | julie.irving@newcastle.ac.uk | UK |
Alexander Popov | uralcytometry@gmail.com | Russia |
Chi-Kong Li | ckli@cuhk.edu.hk | Hong Kong + China |
Katalin Csernus | cs-kata@freemail.hu | Hungary |
Mónica López Duarte | monica.lopez@scsalud.es | SEHOP (Spain) |
Toshihiko Imamura | imamura@koto.kpu-m.ac.jp | Japan |
Jean-Pierre Bourquin | jean-pierre.bourquin@kispi.uzh.ch | Switzerland |
International BFM study group: https://bfminternational.wordpress.com/