Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15–29 years during 1984–94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984–88 and 1989–94 for those aged 15–19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984–88 and 1989–94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group. © 1999 Cancer Research Campaig

Overlooked post-translational modifications of proteins in Plasmodium falciparum: N- and O-glycosylation - A Review

Human malignant malaria is caused by Plasmodium falciparum and accounts for almost 900,000 deaths per year, the majority of which are children and pregnant women in developing countries. There has been significant effort to understand the biology of P. falciparum and its interactions with the host. However, these studies are hindered because several aspects of parasite biology remain controversial, such as N- and O-glycosylation. This review describes work that has been done to elucidate protein glycosylation in P. falciparum and it focuses on describing biochemical evidence for N- and O-glycosylation. Although there has been significant work in this field, these aspects of parasite biochemistry need to be explored further

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin.

Twelve men with louse-borne relapsing fever were treated with single doses of procaine penicillin plus aluminum monostearate (PAM) intramuscularly or of tetracycline intravenously. All patients experienced a definite Jarisch-Herxheimer-like reaction. Fever and spirochetemia were significantly prolonged and peak temperature was lower and occurred later in the PAM-treated group. Peak pulmonary ventilation, metabolic rate, and arterial PO2 were significantly higher in the tetracycline-treated group. Circulatory changes were similar in the two groups but were prolonged in the PAM-treated patients. Thus, tetracycline is recommended for treatment because it is more rapidly effective in eliminating Borrelia spirochetes and produces a reaction no more stressful physiologically than the one after PAM. There was no evidence of complement activation, and there was no change in immunoglobulin levels throughout the reaction. Immune complexes were detected in serum of five patients before treatment, but in fewer patients at the peak of the reaction and subsequently