ALL-IC relapsed ALL project
The Acute Lymphoblastic Leukaemia Inter Continental (ALL-IC) Study Group has completed its second frontline ALL trial. By standardizing therapy and involving flow cytometry based MRD in treatment stratification, patient outcomes improved further. Still 15-20% of patients relapse. When looked up in 2013, survival of relapsed patients in the ALL-IC Study Group lagged behind that achieved in best contemporary studies. Hence, a project was started specifically dedicated to improve ALL 1st relapse results. This is the ALL-IC REL project, by the ALL-IC REL Study Group. There is much but not total overlap between countries / centres joining the 1st line ALL-IC trials and the ALL-IC REL project.
- Dániel Erdélyi, Semmelweis University, Budapest, Hungary (Chair from 2023)
- Janez Jazbec, Ljubljana University Medical Centre, Ljubljana, Slovenia (Chair between 2014-2022)
- Juan Tordecilla, Clinica Santa Maria, Santiago, Chile
- Marko Kavčič, University Medical Centre, Ljubljana, Slovenia
- Monica Makiya, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
- Sophia Polychronopoulou, Aghia Sophia Children’s Hospital, Athens, Greece
- Volkan Hazar, Memorial Health Group Medstar Yildiz Hospital, Antalya, Turkey
- Monica Makiya, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina (firstname.lastname@example.org)
- Dobrin Konstantinov, University Hospital “Tsaritsa Johanna-ISUL”, Sofia, Bulgaria (email@example.com)
- Boryana Avramova, University Hospital “Tsaritsa Johanna-ISUL” , Sofia Quin Joanna University Hospital, Plovdiv, Bulgaria (firstname.lastname@example.org)
- Juan Tordecilla, Clinica Santa Maria, Santiago, Chile (email@example.com)
- Andrea Reyes, Hospital Robert de Rio, Santiago, Chile (firstname.lastname@example.org)
- Ernest Bilić, University Hospital Centre Zagreb, Zagreb, Croatia (email@example.com)
- Zrinko Šalek, University Hospital Centre Zagreb, Zagreb, Croatia (firstname.lastname@example.org)
- Tamar Javakhadze, Iashvili Children Central Hospital, Tbiliszi, Georgia (email@example.com)
- Keso Mamageishvili, Iashvili Children Central Hospital, Tbiliszi, Georgia (firstname.lastname@example.org)
- Sophia Polychronopoulou, Aghia Sophia Children’s Hospital, Athens, Greece (email@example.com)
- Mirella Ampatzidou, Aghia Sophia Children’s Hospital, Athens, Greece (firstname.lastname@example.org)
- Dániel Erdélyi, Semmelweis University, Budapest, Hungary (email@example.com)
- Anna Mohas, Semmelweis University, Budapest, Hungary (firstname.lastname@example.org)
- Veronika Enzsol, Heim Pal Children’s Hospital, Budapest, Hungary (email@example.com)
- Babak Abdolkarimi, Lorestan University of Medical Sciences, Khorramabad, Iran (firstname.lastname@example.org)
- Roula Farah, Lebanese American University, Beirut, Lebanon (email@example.com)
- Anca Colita, “Carol Davila” University of Medicine and Pharmacy, Fundeni Clinical Institute, Bucharest, Romania (firstname.lastname@example.org)
- Letitia Elena Radu, “Carol Davila” University of Medicine and Pharmacy, Fundeni Clinical Institute, Bucharest, Romania (email@example.com)
- Milos Kuzmanovic, University of Belgrad, Belgrad, Serbia (firstname.lastname@example.org)
- Janez Jazbec, Ljubljana University Medical Centre, Ljubljana, Slovenia (email@example.com)
- Marko Kavčič, University Medical Centre, Ljubljana, Slovenia (firstname.lastname@example.org)
- Tomaz Prelog, Ljubljana University Medical Centre, Ljubljana, Slovenia (email@example.com)
- Aida Zeckanovic, Universitats-Kinderspital Zürich, Zürich, Switzerland (firstname.lastname@example.org)
- Volkan Hazar, Memorial Health Group Medstar Yildiz Hospital, Antalya, Turkey (email@example.com)
- Koray Yalçın, Bahcesehir University Medical Park Göztepe Hospital, Istanbul, Turkey (firstname.lastname@example.org)
- Luis Castillo, Fundación Perez Scremini, Montevideo, Uruguay (email@example.com)
The group introduced a unified treatment protocol (ALL-IC REL 2016) addressing first relapse cases. The protocol used the IntReALL 2010 SR and HR study standard arms, with minor changes, as best available practice guidance for ALL-IC countries. As flow-cytometric determination of minimal residual disease was already an integral part of ALL-IC 2002 and 2009 studies and is a technology available, standardised, quality controlled in ALL-IC countries, flow-cytometry is used for assessment of treatment response in this protocol.
As per the knowledge of the steering committee, this guidance is applied in the following countries, either in all or just some of the centres: Argentina (GATLA), Bulgaria, Chile, Croatia, Georgia, Greece, Hungary, Lebanon, North Macedonia, Romania, Serbia, Slovenia, Turkey and planned to be applied in Iran.
A common registry was also established in REDCap platform. Pseudonimised patient data are entered here with follow up MRD values, toxicity grading and data on outcome.
In 2021, we presented preliminary results at the virtual Childhood Leukemia and Lymphoma Conference (CLLS 2021, 11th– 12th March 2021):(https://semmelweis.hu/tuzoltoklinika/files/2022/05/ALL-.IC-REL_e-poster_CLLS-2020-2021_v4.pdf)
Results of a larger cohort with longer follow up and subgroup analyses are being prepared in the format of an original journal article.
The latest 2019 protocol version is available at the following link: https://semmelweis.hu/tuzoltoklinika/files/2022/05/ALL-IC-REL-2016_v1.1_2019-09-16.pdf
As of 2022, a protocol update is being prepared to optimize patient stratification, to include new immunotherapies and to provide salvage options for patients who don’t or poorly respond. An outline is available so far for download. We recommend applying these changes even before the full guidance is written up.
A tumour board with monthly online meetings started in June 2022. All international colleagues are welcome to take part and to present their difficult resistant / relapsed ALL cases for debate. If interested, please contact Dr Anna Mohás (firstname.lastname@example.org) to get access and to get on the mailing list. Please use the below form for submitting case summaries
Case submission form ALLICREL-Tuboard_2023-02-06
The ALL-IC REL study group would welcome further centres or countries to join. The protocol is open for use to anyone. We encourage non-ALL-IC members, too, to use the registry and upload data of patients treated (even just partly) along this protocol. The register is at REDCap, a free secure IT platform, all users can download their own uploaded data any time.
For access to the registry, please email Marko Kavcic at email@example.com