Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

Abstract

We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis. The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients' event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address.

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

“…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].…”

Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation

“…Rizzari and colleagues showed that trough asparaginase activity levels of < 0.05 IU/mL, obtained either with native E. Coli or Erwinia asparaginase, resulted in serum and CSF asparagine depletion in children with ALL. 25 In some studies activity levels as low as 0.02 IU/mL 26,27 or 0.03 IU/mL 21,28 resulted in sufficient depletion. In contrast, the only study indicating that higher activity levels are needed is a recent COG study of two pegylated E. coli asparaginase preparations, calaspargase pegol and pegaspargase, in which the plasma asparagine level began…”

Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15][23][24][25][26] As typified by these randomized clinical trials where statistically significant differences in outcomes were found between treatment regimens, improvement has generally been observed with intensified therapy, but the impact of treatment intensification has been more apparent on EFS than survival.…”

“…1 Long-term survival has become the reality for the majority of children diagnosed with ALL, with approximately 85% surviving 5 years or longer after diagnosis. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] However, depending on certain risk factors, such as age at diagnosis, presenting white blood cell (WBC) count, hematopoietic lineage of the disease, and cytogenetic abnormalities, approximately 20% will experience relapse, 2-15 most of whom are destined to die of their disease. [16][17][18][19][20][21][22] Because of the relatively high prevalence of newly diagnosed ALL, relapsed ALL itself remains a common malignancy and a major cause of death among children.…”