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Cancer. 2018 Dec 1;124(23):4538-4547. doi: 10.1002/cncr.31758. Epub 2018 Oct 10.

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG-ALL-2002 study.

Author information

1
Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
2
Department of Hematology-Oncology, Chang Gung Children's Hospital-Linkou and Chang Gung University, Taoyuan, Taiwan.
3
Department of Pediatrics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
4
Division of Pediatric Hematology and Oncology, China Medical University Children's Hospital, Taichung, Taiwan.
5
Department of Biotechnology, Asia University, Taichung, Taiwan.
6
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
7
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
8
Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
9
Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.
10
Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.
11
Department of Pediatrics, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan.
12
Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
13
Department of Pediatrics, Chia-Yi Christian Hospital, Chiayi, Taiwan.
14
Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
15
Department of Pediatrics, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
16
Division of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan.
17
Department of Pediatrics, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan.
18
Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
19
Childhood Cancer Foundation, Taipei, Taiwan.

Abstract

BACKGROUND:

To eliminate cranial irradiation (CrRT)-related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)-directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL).

METHODS:

This study compared the treatment outcomes of patients overall and patients with a non-CNS-1 status (CNS-2, CNS-3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG-ALL-2002 protocol by the introduction of the modification (era 1 [2002-2008] with CrRT and era 2 [2009-2012] with delayed first TIT and no CrRT).

RESULTS:

There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5-year event-free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non-CNS-1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5-year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2.

CONCLUSIONS:

The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non-CNS-1 status.

KEYWORDS:

acute lymphoblastic leukemia; central nervous system; children; cranial irradiation; intrathecal chemotherapy

PMID:
30303520
DOI:
10.1002/cncr.31758

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