Prospective study of thromboembolism in 1038 children with acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology (NOPHO) study.

UNLABELLED: ESSENTIALS: Children with acute lymphoblastic leukemia (ALL) are at risk of thromboembolism (TE). This is a prospective evaluation of the incidence, risk factors and outcomes of TE in 1038 children with ALL. TE occurred in 6.1% of children, with the highest incidence (20.5%) among those aged 15-17 years. A TE-associated case fatality of 6.4% indicates that TE is a severe complication of ALL treatment. BACKGROUND: Thromboembolism (TE) is a major toxicity in children with acute lymphoblastic leukemia (ALL) and may have a negative impact on ALL treatment. OBJECTIVES: To examine the cumulative incidence, outcomes and risk factors associated with TE in children with leukemia. PATIENTS/METHODS: We prospectively evaluated TE in 1038 Nordic children and adolescents (≥ 1 and < 18 years) diagnosed with ALL during 2008-2013 and treated according to the NOPHO (Nordic Society of Pediatric Hematology and Oncology)-ALL 2008 protocol. The cohort was followed until December 2014. Cox proportional regression was used to compute hazard ratios (HRs). RESULTS: TE events (n = 63) occurred most frequently in conjunction with asparaginase (ASP) administration (52/63). The cumulative incidence of TE was 6.1% (95% confidence interval [CI], 4.8-7.7). Being aged 15-17 years was associated with an increased risk of TE (adjusted HR of 4.0; 95% CI, 2.1-7.7). We found a TE-associated 30-day case fatality of 6.4% (95% CI, 1.8-15.5) and TE-related truncation of ASP therapy in 36.2% (21/58). Major hemorrhage occurred in 3.5% (2/58) of anticoagulated patients. Minor hemorrhage was reported in two out of 58 patients. No major bleeds occurred in children who received low-molecular-weight heparin. CONCLUSIONS: Methods to identify children and adolescents who will benefit from thromboprophylaxis during ALL treatment are called for. The truncation of ASP should be avoided. The long-term survival outcomes for ALL patients with TE require close monitoring in the future.

Prenatal diagnosis of haemophilia in Sweden now more commonly used for psychological preparation than termination of pregnancy.

The aims of the study were to define the frequency, outcome and reasons for prenatal diagnosis (PND) in Sweden during a 30-year period in order to study trends and changes. The study population, from the Swedish nationwide registry of PND of haemophilia, consisted of 54 women, compromising >95% of all, who underwent PND (n = 90) of haemophilia during 1977-2013. PND was performed by amniocentesis (n = 10), chorionic villus sampling (n = 64) or by analysis of foetal blood (n = 16). A total of 27/90 foetuses were found to have haemophilia. Sixteen went to termination and the remaining 11 were born during the end of the study period (2000-2013). Three of 90 pregnancies were terminated due to findings other than haemophilia and 3/90 PNDs led to miscarriage. In the 30 families with known haemophilia, PNDs (n = 55) were used in 27/55 cases for 'psychological preparation' and in 23/55 cases with the aim to terminate the pregnancy. A subgroup of women (n = 17) who consecutively underwent PND in the years 1997-2010 were further interviewed. For 11/17, being a carrier had a negative effect on the decision to become pregnant, and in 11 cases PND had influenced their decision to conceive. Our study show that PND of haemophilia is stable over time but increasingly used during the last decade as a psychological preparation for having a child with haemophilia as compared to earlier where more terminations of pregnancies were conducted.

Reproductive choices of haemophilia carriers.

The actual reproductive choices made by slightly over a quarter of all the carriers of severe or moderate haemophilia in Sweden were investigated and compared with those of a randomly selected age-matched group of women who were not carriers of haemophilia. In general, the 105 carriers had the same number of children as other women of similar age. However, carriers who did not choose prenatal diagnosis (PD) often abstained from further pregnancies after the birth of a haemophilic child, and they had significantly fewer children than the remainder of the carriers, as well as fewer children than women in the control group. Logistic regression analysis showed choice of PD to be correlated to a positive attitude towards abortion following PD and a family history of haemophilia. Carriers who have experienced the complications of haemophilia or its treatment appear to be more in favour of PD than women whose haemophilic children have received modern treatment without complications.

Long-term psychological effects of carrier testing and prenatal diagnosis of haemophilia: comparison with a control group.

The long-term psychological effects resulting from carrier testing and prenatal diagnosis (PD) of haemophilia were evaluated by comparing mental symptomatology scores (Symptom Check List, SCL-90) for 50 carriers of haemophilia who had undergone PD about five years earlier, 55 carriers who had not undergone PD and 262 control women who were not carriers. All of the women had children. Carrier testing for haemophilia per se and in combination with PD does not appear to have negative long-term psychological effects. A low tendency for somatization seems to be a factor characteristic of carriers considering PD for haemophilia and it was particularly salient when carriers had to consider the more invasive late PD procedures (amniocentesis and fetal blood sampling). Women who performed late PD appeared to represent a positive selection of carriers for whom a good sense of coherence and social support protected them from negative long-term psychological effects. It is reassuring that early PD by CVS, which is the current method of choice for PD for haemophilia, did not appear to have negative long-term psychological effects, even for women who had had an early abortion following PD.

How do carriers of hemophilia and their spouses experience prenatal diagnosis by chorionic villus sampling?

A semistructured personal interview with 29 female carriers of hemophilia and 23 of their spouses was performed at a median of 3 1/2 years after the first chorionic villus sampling (CVS) and gene analysis. Carriers with a hemophilic father or brother, had high sense of coherence (SOC) scores, and thus would be expected to have good ability to handle the stress of prenatal diagnosis (PD). Prenatal diagnosis of hemophilia by CVS was generally well accepted by the women and their spouses. However, the period while waiting for test results was experienced as emotionally troublesome by both the women and their spouses; women reporting significantly more psychiatric or psychosomatic symptoms than men. Positive effects resulting from participation by the spouse on how the women experienced PD could not be identified. Selective abortion after first trimester PD was clearly experienced as emotionally painful by both the women and their spouses, these reactions being similar to, but not as pronounced as those found after second trimester selective abortion. Notably, signs of depressive mood were observed several years after the abortion, and the provision of psychosocial support should be recommended for couples who decide upon termination of pregnancy following PD.

Carrier testing and prenatal diagnosis of haemophilia--utilisation and psychological consequences.

Attitudes towards prenatal diagnosis, and abortion vary widely between different countries, religions, cultures and over time. Carrier testing and prenatal diagnosis (PD) of haemophilia have become an integrated part of the comprehensive care for haemophilia in Sweden as well as in many other countries. Almost all carriers are interested in carrier testing if they are aware of the possibility. With the development of PD by chorionic villus sampling in the first trimester, the method became acceptable for many carriers, and it has in Sweden actually had an effect on the incidence of haemophilia in the 1990s. The use of PD is more common among women who perceive haemophilia as a very serious disease and who have a positive attitude towards legal abortion. The main reason for carriers not to use PD was that they do not find haemophilia to be a sufficiently serious disorder to justify an abortion. Women and their spouses are under a great deal of psychological pressure in association with the PD procedure, and the psychological consequences of having to terminate a pregnancy are long-lasting. At follow-up, about 6 years after PD and abortion, these women, however, do not have more signs of psychological distress than women without PD experience. Nevertheless, they must be offered qualified assistance both before and after PD as well as adequate follow-up after an abortion to help them cope with the emotional strain they are under.

Identifying carriers at high risk for negative reactions when performing prenatal diagnosis of haemophilia.

The aim of the current study was to determine which pregnant carriers of haemophilia are at particularly high risk for having notably negative psychological reactions in association with prenatal diagnosis (PND) by fetal blood sampling of offspring haemophilia. Among 29 carriers of haemophilia A or B, notable psychiatric or psychosomatic symptoms in association with PND were significantly related to the woman's having a negative view of herself in general and of being a gene carrier, a planned pregnancy, high education, a good general knowledge of haemophilia and a guiding philosophy of life. Women with strong negative reactions significantly more often reported signs of depressive mood at follow-up. The results suggest that giving more information and promoting increased knowledge about the disease and the PND procedure will, by itself, not help women to cope better emotionally. Provision of prospective psychosocial support is recommended.

How do carriers of hemophilia experience prenatal diagnosis by fetal blood sampling?

A semistructured personal interview was performed with 29 carriers of hemophilia A or B, 1-4 years after a pregnancy in which prenatal diagnosis (PND) of hemophilia was performed by fetal blood sampling. The carriers had received different recommendations regarding future pregnancies, and 14/29 did not know before they became pregnant that PND by fetal blood sampling was possible. One third of the women felt that important information was lacking in the consultations that preceded the PND. The conclusions regarding future genetic counselling are that more attention should be paid to improving education of all female carriers before a pregnancy, to motivating fathers-to-be to attend counselling sessions with the carriers, and to emphasizing the importance of the emotional support given by the family doctor and by other females who have experienced PND.

Muco-epidermoid tumour of the bronchus.

A 7-year-old boy with recurrent pneumonia of the right lower lobe is described. At bronchoscopy a small tumour almost totally obliterating the right lower lobe was detected. Surgical treatment was undertaken. Histopathologic studies showed findings consistent with those of a muco-epidermoid tumour. The case emphasizes bronchoscopy as an important investigation in children with recurrent pneumonia. It also shows the importance of performing the bronchoscopy during a prolonged course of antibiotic prophylaxis in order to ensure a minimum of infected mucus within the bronchi. This report is completed with a short review of the literature on muco-epidermoid tumours of the bronchus in children. Their favourable prognosis and very low malignant potential is underlined.