Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia

Abstract

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P ¼ 0.0004) over this period, 69.3±1.9% in 1997-2001 to 77.4±1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy 450 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy 450, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

“…Written informed consent was obtained from the patients or their families. The diagnosis of T-cell ALL was based on bone marrow aspiration and immunophenotyping with monoclonal antibodies directed to T-lineageassociated antigens [7]. Between January 1997 and August 2010, 45 pediatric patients with T-cell ALL were enrolled from six medical centers in Taiwan.…”

“…All were treated according to the TPOG protocols. Patients received TPOG-ALL-97 VHR for chemotherapy if they were diagnosed between January 1997 to December 2001, and TPOG-ALL-2002 VHR if they were diagnosed between January 2002 and August 2010 [7]. The TPOG-ALL-2002 VHR protocol differed from TPOG-ALL-97 VHR (activated in January 1997) in prednisolone (decreased from 60 to 40 mg/m 2 / day) and dexamethasone (decreased from 8 to 6 mg/m 2 /day) [7].…”

“…Although the use of intensive chemotherapy has enabled patients with T-cell ALL to fare as well as patients with B-cell precursor ALL in some studies, the outcomes are significantly worse for the patients with T-cell ALL in most treatment protocols [3][4][5][6][7][8][9][10][11][12][13][14][15]. Chromosomal alterations, including numbers and translocations, have helped to classify pediatric patients with B-cell precursor ALL and improve treatment outcomes in the past three decades [16].…”

Clinical features, molecular diagnosis, and treatment outcome of infants with leukemia in Taiwan

“…Only 1 out of 23 infants (4.3%) with ALL received hematopoietic stem cell transplantation as part of their therapy in this study. This is close to the 2% of patients with ALL treated according to the TPOG-ALL-2002 protocol [11]. However, the role of hematopoietic stem cell transplantation in the management of infants with leukemia is still unclear [36,37].…”

“…Three consecutive nationwide TPOG-911, TPOG-ALL-97 VHR, and TPOG-ALL-2002 VHR protocols were used to treat infants with ALL [9][10][11]. The TPOG-911 protocol was modified from the New York Regimen [12].…”