Immunosuppressive thiopurines like azathioprine, 6-mercaptopurine, and thioguanine are commonly used in inflammatory and neoplastic disorders. A subset of these patients are genetically slow metabolizers due to point-mutations in enzyme thiopurine S-methyltransferase (TPMT), and are at a higher risk of hematologic toxicity and leukemogenesis. We present such a patient who was a slow metabolizer for azathioprine, and developed a rapidly lethal form acute myeloid leukemia after relatively low dose exposure to the drug. There was prominent hemophagocytic activity in the bone marrow, and cytogenetic analysis showed a complex karyotype with monosomy 7, but no involvement of chromosome 8. Am. J. Hematol. 83:80-83, 2008. V
Catecholamines and their metabolites are important in the diagnosis of neuroblastoma (NB). Plasma (p-) levels of 3,4-dihydroxyphenylalanine (DOPA) are increased in most NB, probably reflecting decreased DOPA decarboxylase activity. Urine (u-) homovanillic acid (HVA), a DOPA and dopamine (DA) metabolite. is also increased in most NB. DOPAC (3,4-dihydroxyphenylacetic acid) is an important metabolite of DA in tissues with monoamine oxidase (MAO) activity. Because MAO is expressed in NB tumor cells, we studied the importance of measuring p-DOPAC and p-DOPA as compared to u-HVA and u-vanillylmandelic acid (VMA) in the diagnosis and follow-up of NB. DOPAC, DOPA, dopamine, noradrenaline, adrenaline, VMA and HVA were measured by reverse-phase HPLC with electrochemical detection in 106 children (28 with NB (13 newly diagnosed), 25 with other solid tumors, 28 hospitalized for nonneoplastic diseases, and 25 healthy children). P-DOPAC or p-DOPA concentrations were above the upper normal range in 92% of untreated NB patients, as were u-HVA or u-VMA levels. None of these tumor markers was correlated to tumor stage or survival. P-DOPA but not p-DOPAC was correlated to age in NB children. Increased values of p-DOPAC and p-DOPA were found in one patient surviving NB for 10 years. Plasma DOPAC concentrations were decreased in children hospitalized for non-NB diseases, probably reflecting reduced food intake. Plasma analyses of DOPA and DOPAC seem to be useful alternatives in the diagnosis and follow-up of NB if urine sampling is to be avoided. Plasma DOPAC may be an index of nutritional status in various diseases.
Study question Is the rate of fatherhood among men diagnosed with cancer in childhood and early adulthood different from men without cancer – have differences changed over time? Summary answer Men diagnosed with cancer had significantly reduced rates of fatherhood compared with undiagnosed men. Rates of fatherhood among the cancer survivors increased markedly over time. What is known already The number of children and young adolescents who survive cancer has steadily increased over the past decades, with a current 5-year survival rate of approximately 80%. Consequently, life circumstances after cancer have gained increasing importance, including the desire among survivors to have children and a family. MAR technologies to aid reproduction among cancer survivors have been developed, and fertility preservation is increasingly a topic being discussed before undergoing cancer treatment. But the potential for fertility preservation differs depending on age at diagnosis and type of cancer. Earlier studies have shown decreased fertility rates among survivors of childhood and adolescent cancer. Study design, size, duration This study is a national, register-based cohort study. Men diagnosed with cancer in childhood and early adulthood (<30 years of age) were registered in the Danish Cancer Register in 1978–2016 (n = 15,600). At time of diagnosis, each cancer-diagnosed man was randomly age-matched with 150 undiagnosed men from the background population within the same birth year. The men were followed in medical registers and socio-demographic population registers until death, migration or end of study December 31st, 2017. Participants/materials, setting, methods Fatherhood among the boys and young men diagnosed with cancer was compared with the age-matched comparison group in all statistical analyses. Cancer diagnoses were categorized as central nervous system (CNS), haematological cancers or solid cancers. Also, analyses were stratified by age at diagnosis (0–9, 10–19, 20–29 years) and year of diagnosis (1978–89, 1990–99, 2000–16). Death was incorporated as a competing risk in all analyses. Main results and the role of chance The study population consisted of 15,600 boys and young men diagnosed with cancer between 1978 and 2016 and 1,386,493 men in the age-matched comparison group. Men surviving CNS cancer had the lowest hazard ratio of fatherhood compared with the age-matched comparison group (HR = 0.64, 95% CI 0.57–0.73), followed by survivors of haematological cancers (HR = 0.90, 95% CI 0.82–0.98) while the highest chance of fatherhood was slightly increased among survivors of solid cancers (HR = 1.13, 95% CI 1.10–1.16). The hazard ratio of becoming a father increased over time. From the first decade to the last decade 30 years later, the hazard ratio of becoming a father increased for solid tumours (HR 0.76, 95% CI 0.72–0.80 to HR 1.07, 95% CI 0.96–1.19), haematological tumours (HR 0.60, 95% CI 0.51–0.71 to HR 0.97, 95% CI 0.76–1.23) and CNS tumours (HR 0.47, 95% CI 0.39–0.58 to HR 1.04, 95% CI 0.56–1.93) compared to the age-matched comparison group. Also, men diagnosed with cancer when aged 20–29 years more likely became fathers over time (HR 0.79, 95% CI 0.74–0.84 to HR 1.09, 95% CI 0.98–1.22). Limitations, reasons for caution The study was based on register data, and information was not available about the men’s fertility potential, whether they had a desire to have children and whether it was possible for them to find a partner. Also, information about fertility preservation, e. g. sperm freezing, could have provided additional insights. Wider implications of the findings: Information and education of male patients diagnosed with cancer about fertility preservation options, and chances to create their own family is crucial. Reassuringly, time trends showed more men with a previous cancer diagnosis becoming fathers in recent years than earlier, reflecting that survival and fertility preservation have improved over time. Trial registration number N/A
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