Day 15 and Day 33 Minimal Residual Disease Assessment for Acute Lymphoblastic Leukemia Patients Treated According to the BFM ALL IC 2009 Protocol: Single-Center Experience of 133 Cases

Letitia-Elena Radu; Andrei Colita; Sergiu Pasca; Ciprian Tomuleasa; Codruta Popa; Catalin Serban; Anca Gheorghe; Andreea Serbanica; Cristina Jercan; Andra Marcu; Ana Bica; Patric Teodorescu; Catalin Constantinescu; Bobe Petrushev; Minodora Asan; Cerasela Jardan; Mihaela Dragomir; Alina Tanase; Anca Colita

doi:10.3389/fonc.2020.00923

Day 15 and Day 33 Minimal Residual Disease Assessment for Acute Lymphoblastic Leukemia Patients Treated According to the BFM ALL IC 2009 Protocol: Single-Center Experience of 133 Cases

Front Oncol. 2020 Jun 30:10:923. doi: 10.3389/fonc.2020.00923. eCollection 2020.

Authors

Letitia-Elena Radu^{1

2}, Andrei Colita^{1

3}, Sergiu Pasca^{4

5}, Ciprian Tomuleasa^{4

5

6}, Codruta Popa^{1

2}, Catalin Serban², Anca Gheorghe², Andreea Serbanica^{1

2}, Cristina Jercan^{1

2}, Andra Marcu², Ana Bica², Patric Teodorescu^{4

6}, Catalin Constantinescu^{4

6}, Bobe Petrushev⁷, Minodora Asan², Cerasela Jardan^{1

2}, Mihaela Dragomir², Alina Tanase², Anca Colita^{1

2}

Affiliations

¹ Department of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
² Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
³ Department of Hematology, Coltea Hospital, Bucharest, Romania.
⁴ Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
⁵ Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
⁶ Department of Hematology, Oncology Institute Prof. Dr. Ion Chiricuta, Cluj Napoca, Romania.
⁷ Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.

Abstract

Introduction: Childhood acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the acquisition of several genetic lesions in the lymphoid progenitors with subsequent proliferation advantage and lack of maturation. Along the years, it has been repeatedly shown that minimal residual disease (MRD) plays an important role in prognosis and therapy choice. The aim of the current study was to determine the prognostic role of MRD in childhood ALL patients in conjunction with other relevant patient and disease characteristics, thus showing the real-life scenario of childhood ALL. Patients and Methods: The retrospective study includes childhood ALL patients that were treated according to the BFM ALL IC 2009 between January 2016 and December 2018 at the Fundeni Clinical Institute, Bucharest, Romania. Results: None of the variables significantly influenced the induction-related death in our study. None of the variables independently predicted relapse-free survival (RFS) with the highest tendency for statistical significance being represented by poor prednisone response. Non-relapse mortality (NRM) was independently predicted by age, prednisone response, and day 33 flow cytometry-MRD (FCM-MRD). Overall survival (OS) was independently predicted by prednisone response and day 33 FCM-MRD. Event-free survival (EFS) was independently predicted by age, prednisone response, and day 33 FCM-MRD. Conclusion : Prednisone response, day 15 FCM-MRD, day 33 FCM-MRD, and the risk group represent the most important factors that in the current study independently predict childhood ALL prognosis.

Keywords: ALL; MRD; children; flow cytometry; survival.