Progress against childhood and adolescent acute lymphoblastic leukaemia in the Netherlands, 1990-2015.

We assessed the epidemiologic progress against childhood and adolescent acute lymphoblastic leukaemia (ALL) in the Netherlands over a 26 year period. ALL patients <18 years were selected from the Netherlands Cancer Registry and the Dutch Childhood Oncology Group. Trend analyses were performed over time and by age group and ALL subtype. Between 1990 and 2015, 2997 ALL patients were diagnosed, i.e. 115 patients (range 87-147) per year. Overall incidence remained stable at 37 per million children, despite increases for B-cell precursor ALL (BCP-ALL) at age 10-14 years (AAPC + 1.4%, p = 0.04) and T-cell ALL at 15-17 years (AAPC + 3.7%, p = 0.01). Five-year survival increased from 80% in 1990-94 to 91% in 2010-15 (p < 0.01). Mortality decreased by 4% annually (p < 0.01). Patients 15-17 years were increasingly treated in a paediatric oncology centre, from 35% in 1990-94 to 87% in 2010-15 and experienced a 70% reduction of risk of death compared to those treated outside such a centre (p < 0.01). Significant progress against childhood ALL has been made in the Netherlands, visible by improved survival rates coinciding with declining mortality rates. These outcomes were accompanied by stable incidence rates, despite increases for BCP-ALL at age 10-14 years and T-cell ALL at age 15-17 years.

Leucemia aguda linfoblástica: de la aminopterina a las células CAR T / Acute lymphoblastic leukemia: From aminopterin to CAR T cells

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Clinical characteristics and analysis of treatment result in children with Ph-positive acute lymphoblastic leukaemia in Poland between 2005 and 2017.

OBJECTIVE: The aim of this study was to analyse the clinical characteristics and outcome of children diagnosed with Ph+ ALL. MATERIAL AND METHODS: A total of 2591 newly diagnosed ALL children were treated in Poland between the years 2005 and 2017. Of those, 44 were diagnosed with Ph(+) ALL. The patients were treated according to protocols: ALL IC-BFM 2002 and 2009 (26 patients), EsPhALL (12 patients), initially ALL IC-BFM and then EsPhALL (6 patients). RESULTS: The median of follow-up in the observed group was 3 years. Overall survival (OS) and event-free survival (EFS) of Ph+ ALL group were 0.73 and 0.64. OS and EFS of patients after HSCT were 0.78 and 0.66, while without HSCT were 0.6 and 0.6, P = 0.27 and 0.63. OS was 0.8 for patients treated with chemotherapy plus imatinib and 0.61 for chemotherapy alone, P = 0.22, while EFS was 0.66 (imatinib therapy) and 0. 61 (without imatinib), P = 0.41. CONCLUSION: Our study suggests that adding imatinib to intensive chemotherapy seems to improve outcome. However, this study was limited by a small number of patients and a variety of chemotherapy regimens with or without imatinib.

Lessons from 50 years of curing childhood leukaemia.

One of the great success stories of modern medicine is undoubtedly the remarkable improvement in outcome for childhood cancer, achieved through the work of the co-operative groups enrolling patients in randomised controlled trials. In 1965, survival was almost zero; now 5-year survival rates exceed 80% in high-income countries. The lessons learned in the care of patients with the most common malignancy in childhood--acute lymphoblastic leukaemia--have been used in all other cancers of childhood and more recently in the management of adults. These lessons can be broadly applied in medical practice, because elements of laboratory science in all branches of pathology, as well as a deep understanding of biochemistry, physiology, pharmacology, genetics and molecular science, run through this story. Far from being a sad area of practice, paediatric haematology and oncology remains the champion of embedded clinical and translational research, diagnosis from bench to bedside and lifelong multidisciplinary management of the child and their family.

Discovery of why acute lymphoblastic leukaemia cells are killed by asparaginase: Adventures of a young post-doctoral student, Bertha K Madras.

A surprising finding was made by JG Kidd (1909-1991) that guinea pig serum could make tumours disappear in mice. A later finding made by JD Broome (1939-) showed that asparaginase could suppress or kill tumour cells. However, the major mystery was why were only tumour cells but not normal cells affected by the asparaginase? The biology underlying this mechanism was unravelled by a young post-doctoral student, Bertha K Madras (1942-) who hypothesized that cells with low asparagine synthetase are those that die following treatment with asparaginase. To test her theory, Madras developed an assay for asparagine synthetase. The hypothesis was supported by the results that cells with normal asparagine synthetase were protected, while cells with low levels of this enzyme were killed by asparaginase. The findings provide a clinical guide for the use of asparaginase in acute lymphoblastic leukaemia in children and adults.

Survival improvement by decade of patients aged 0-14 years with acute lymphoblastic leukemia: a SEER analysis.

To evaluate treatment outcomes in children with acute lymphoblastic leukemia (ALL) over the past 3 decades, we assessed the survival of children with ALL in the Surveillance, Epidemiology, and End Results (SEER) database. Among 12,096 patients from 18 SEER sites diagnosed from 1981 to 2010, survival rates improved each decade from 74.8% to 84.5% to 88.6% at 5 years and from 69.3% to 80.9% to 85.5% at 10 years (P < 0.0001). For ages 10-14 years, 10-year survival increased by more than 20 percentage points to 75.3%, but for infants, it remained low at 54.7%. Improvements in survival rates were observed in both sexes, but survival rates were higher in girls than in boys. For ages 0-14 years during the 2001-2010 period, the 10-year relative survival rates were 87.8% in girls and 83.6% in boys (P < 0.01). Survival rates in child with ALL are expected to further improve with continuous advance in therapies such as targeted therapy and personalized therapy.

[Acute lymphoblastic leukemia in children: history of drug therapy management]. / La leucémie aiguë lymphobtastique chez l'enfant: évolution de la pharmacothérapie.

The last forty years have witnessed major improvements in the survival of pediatric cancer patients with an evolution of acute tymphoblastic leukemia as an untreatable disease to acute lymphoblastic leukemia with a survival rate of more than 90%. This has become possible due to improvements in the various modalities of cancer therapy and supportive care. The aim of this commentary is to give an overview of the history of pharmacological treatment for children with acute Lymphoblastic leukemia.

Differential survival improvement for patients 20-29 years of age with acute lymphoblastic leukemia.

OBJECTIVE: To compare improvement in survival from 1986 to 2009 for acute lymphoblastic leukemia (ALL) patients 1-14, 15-19 and 20-29 years in Ontario and United States. METHODS: This population-based analysis used data from Ontario Cancer Registry (OCR) and Surveillance Epidemiology and End Results (SEER). RESULTS: In OCR, there was steady improvement in survival by period of diagnosis in all three age groups. In SEER, there was no improvement in survival for patients aged 20-29 years. CONCLUSIONS: Survival in Ontario and the United States has improved for patients with ALL aged 1-19 years. However, survival has improved among patients aged 20-29 years only in Ontario.