-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1462 The Different Impacts of an MRD-Guided Protocol on Relapse of Childhood Acute Lymphoblastic Leukemia: The Report of Taiwan Pediatric Oncology Group (TPOG)-ALL-2013

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Diseases, Lymphoid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Hsi-Che Liu, MD1, Shiann-Tarng Jou, MD2*, Shih-Hsiang Chen, MD3, Tang-Her Jaing, MD4*, Ting-Chi Yeh, MD5*, Jiann-Shiuh Chen, MD6*, Kang-Hsi Wu, MD7*, Shih-Chung Wang, MD8*, Chih-Cheng Hsiao, MD9*, Te-Kau Chang, MD10*, Meng-Yao Lu, MD2*, Hsiu-Ju Yen, MD11*, Fang-Liang Huang, MD12*, Shu-Huey Chen, MD13*, Shang-Hsien Yang, MD14*, Yen-Lin Liu, MD15*, Shyh-Shin Chiou, MD, PhD16*, Chao-Ping Yang, MD17*, Lee-Yung Shih, MD18 and Dong-Tsamn Lin, MD2*

1MacKay Memorial Hospital, Taipei, Taiwan
2National Taiwan University Hospital, Taipei, Taiwan
3Chang Gung Memorial Hospital, Taoyuan, TWN
5Mackay Children's Hospital and Mackay Medical College, Taipei, TWN
6Nat'l. Cheng Kung Univ. Hospital, Tainan, TWN
7China Medical University Children's Hospital, Taichung City, TWN
8Changhua Christian Hospital, Changhua, Taiwan
9Chang Gung Memorial Hospital At Kaohsiung, Kaohsiung City, TWN
10China Medical University Children's Hospital, Taichung City, Taiwan
11Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan
12Taichung Veterans General Hospital, Taichung City, TWN
13Taipei Medical University–Shuang Ho Hospital, Taipei, Taiwan
14Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, TWN
15Department of Pediatrics, Taipei Medical University Hospital, Taipei, TWN
16Kaohsiung Medical University Hospital, Kaohsiung City, AL, TWN
17Chang-Gung Children's Hospital, Taoyuan, TWN
18Chang Gung University, Taoyuan, Taiwan

Taiwan Pediatric Oncology Group (TPOG)-ALL-2013 protocol (TPOG-2013), modifying from St. Jude Total Therapy XV Study and Total Therapy XVI Study, was launched since January 2013. This is the first nationwide minimal residual disease (MRD)-directed protocol for treatment of childhood acute lymphoblastic leukemia (ALL) in Taiwan. According to TPOG-2013, two MRD measurements were scheduled on days 15-19 of induction (MRD1 time point, TP1) and days 35-42, end of induction (MRD2 time point, TP2) to make the definitive risk stratification to guide subsequent therapy.

As of April 30, 2023, 814 newly diagnosed ALLs treated with TPOG-2013 and followed up ≥3 years were enrolled in the study. The outcomes were compared with those of TPOG-ALL-2002 protocol (TPOG-2002) (N=1350, between January 2002 and December 2012), which did not integrate the MRD monitoring. The 5-year event-free survival and overall survival were significantly improved from 76% (95% CI, 74-78) and 81% (80-84) of TPOG-2002 to 86% (83-88) and 89% (87-92) of TPOG-2013, respectively (P< 0.0001).

For further analysis of TPOG-2013, 585 (72%) patients with exact adherence (EA) to both TPs were assigned as MRD EA group; 225 patients who were non-adherence (NA) to either one of TPs as MRD NA group; and four patients were excluded for the comparative outcome analysis. For B-cell precursor (BCP) ALL, the 5-year cumulative incidence of relapse (CIR) significantly decreased from TPOG-2002 (N=1194) to TPOG-2013 MRD EA (N=527) (P <0.0001). However, there was no significant improvement of CIR between TPOG-2002 and MRD NA (N=202) (P= 0.21) (Figure 1). In MRD EA of BCP-ALL, compared with TPOG-2002, patients with ETV6::RUNX1 or BCR::ABL1 appeared to have significantly lower CIR. Patients without the common genetic subtypes , denoted as “negative” group, also had significant inferior CIR. And the trend of CIR decrease did not attain significant difference in high hyperdiploidy. In contrast, patients with TCF3::PBX1 or infant with KMT2A-rearrangement did not show CIR improvement (Table 1). In T-ALL, compared with TPOG-2002 (N=156), there was a significant decrease of CIR in TPOG-2013 MRD EA (N=58)(P= 0.01)(Table 1), but not in MRD NA (N=23)(P= 0.86).

There was a longer duration to relapse in MRD EA of BCP-ALL. However, a delay of relapse was only demonstrated in patients with BCR::ABL1, which could be addressed by the introduction of MRD-monitoring and TKI inhibitor in TPOG-2013 (Table 1). Further, in term of early relapse before 1.5 year of remission, there was no significant difference in MRD EA of BCP-ALL, compared with TPOG-2002.

In conclusion, this study demonstrated diffident impacts on relapse according to genetic subtypes and MRD adherence. In the negative group of BCP-ALL without the discovery of novel genetic alternations, the relapse could be much decreased with the MRD-directed treatment protocol.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH