H1N1 infection in children with haematological and oncological diseases in Norway

Aim: To describe the impact of H1N1 infections in children with haematological and oncological diseases during the 2009 H1N1 pandemics. Methods: A short questionnaire was e‐mailed to all paediatric departments taking care of patients with oncological and chronic haematological diseases, asking for known cases of H1N1 infections in this patient group. Results: Nine children treated for cancer and seven children with haematological diseases were registered. No death occurred, but two patients treated for cancer (acute lymphoblastic leukaemia at diagnosis, acute myeloid leukaemia in chemotherapy‐induced bone marrow aplasia) experienced life‐threatening respiratory complications. Conclusion: In all patients with haematological disease and most cases of oncological diseases, the infections ran a mild course. However, life‐threatening complications occurred in severely immunosuppressed and neutropenic patients. Delay of anticancer treatment is a concern even in mild cases.     

Pneumatosis intestinalis in childhood leukaemia. Report of a case with gas in the portal vein and review of the literature

A case of pneumatosis intestinalis (PI) with gas in the portal vein, in an 8-month-old infant with acute lymphatic leukaemia and perforation of the terminal ileum is reported. The 19 previously published cases of PI in pediatric patients with leukaemia are reviewed. The clinical picture and the pathogenetic hypotheses of PI are discussed.     

Encephalopathy in Acute Leukaemia Associated with Methotrexate Therapy

Seven patients are described in whom dementia developed during treatment with methotrexate for meningeal leukaemia. The patients presented with confusion, tremor, ataxia, irritability, and somnolence. There were major epileptic fits in two cases and in one case there was progression to coma and death. Necropsy findings in the latter showed infarcted areas in the temporal and parietal lobes, with no evidence of active leukaemic disease or of viral encephalitis. The condition has not responded to radiotherapy and no positive evidence of viral encephalitis has been obtained. On the other hand, when treated with folinic and folic acid the deterioration has been arrested and there has been some improvement; thus the condition appears to be due to methotrexate. The occurrence of so many cases within the past year of a condition not previously described is probably attributable to the introduction of intensive cytotoxic therapy directed against meningeal leukaemia.     

Metabolism of fibrinogen in children with acute lymphoblastic leukaemia

The metabolism and in vivo kinetics of fibrinogen were studied using homologous ¹²⁵I-labelled fibrinogen in 21 children with acute lymphoblastic leukaemia (ALL). Ten patients were undergoing induction therapy, 11 children were in complete remission on maintenance therapy.Results in the patients undergoing induction therapy were: plasma fibrinogen levels were normal in all except one patient, the plasma fibrinogen pool was elevated in six cases, seven patients had a shortened fibrinogen half-life and increased fractional catabolic rate for fibrinogen. The absolute catabolic rate for fibrinogen was elevated in six cases. This shortened fibrinogen half-life together with the correcting effect of heparinisation on the fibrinogen turnover indicated that fibrinogen was consumed by chronic disseminated intravascular coagulation. Inhibition of the fibrinolytic system with epsilon-aminocaproic acid in five patients had no influence on the fibrinogen half-life in three of them but resulted in its prolongation in two patients.All except two children in complete remission had normal fibrinogen levles. Six patients had elevated plasma fibrinogen pools and in all of the cases survival and fractional catabolic rate of fibrinogen were normal. The absolute catabolic rate for fibrinogen was normal in eight, elevated in three of the patients. This observation indicates that fibrinogen synthesis remains accelerated in some cases of ALL in complete remission, but the cause of this is not known.Abbreviations ALL acute lymphoblastic leukaemia - DIC disseminated intravascular coagulation - PTT partial thromboplastin time - PT prothrombin time - TT thrombin time - EG ethanol gelation test - ELT euglobulin clot lysis time - FDP fibrinogen/fibrin degradation products - FCR fractional catabolic rate constant - ACR absolute catabolic rate - IFP intravascular plasma fibrinogen pool - PV plasma volume     

Acute myeloid leukaemia in patients with trisomy 21 (Down syndrome) treated by bone marrow transplantation

Patients with trisomy 21 have an increased incidence of haematological disorders, including neonatal 'leukaemoid reaction'(transient myeloproliferative disorder [TMD]) and acute leukaemias. In the past it has been felt that patients with trisomy 21 and acute leukaemia do not tolerate, and hence may not warrant, therapy as intensive as those without the syndrome. The present authors' experience and the current literature do not support this view. Two cases are reported of acute myeloid leukaemia in children with trisomy 21, successfully treated with intensive chemotherapy and bone marrow transplantation.     

Development of CNS leukaemia in acute myeloid leukaemia in childhood.

In 130 cases of acute myeloid leukaemia in children below the age of 14 years in Great Britain, there were 21 cases in which the central nervous system was involved. The incidence and timing is similar to that of acute lymphoblastic leukaemia; in a small number of patients who received prophylactic treatment, involvement of the central nervous system was prevented.     

Malignant disease of infancy and childhood with special reference to leukaemia: A survey of 6431 autopsy cases

A study on the prevalence of cancer at autopsy in Chilean children with special reference to leukaemia, was made.In a series of 15300 consecutive autopsies of Chileans, 70% of deceased patients had an autopsy. Of these 15300 cases (male: female ratio 1:0.92) 6431 were children (0–15 years of age); 90% of deceased children patients had an autopsy.The autopsy population of children and adults is a homogeneous ethnic group, and exhibits a low socioeconomic level. Data on the 6431 post-mortem examinations (1945–1966) came from the autopsy records of five hospitals (four of them are teaching hospitals) in the city of Santiago. Each one of the leukaemia and solid tumour cases were diagnosed microscopically.In the children population, 54.92% were males and 45.08% were females. Of the 6431 autopsies, 142 exhibited cancer (2.21%), 2.43% being male cases and 1.93% being female cases. The autopsy cases showed a marked excess of boys (73.92%) and girls (69.77%) under 1 year of age. The prevalence of major morphological groups of cancer was as follows: leukaemias 50.70%, intracranial and other neural neoplasms 25.35%, malignant lymphomas, including Hodgkin's disease, 14.07%, and mixed malignant tumours (Wilms' tumour) 4.93%. Acute leukaemias (42.96%), medulloblastoma (7.65%), Hodgkin's disease (6.34%), Wilms' tumour (4.93%), and lymphosarcoma (4.93%) were the most prevalent types of cancer. Leukaemia cases had a corrected male: female ratio of 1:0.61. The prevalence of leukaemia in the autopsy population was 1.12%.This investigation was supported in part by an American Cancer Society Grant.     

Transient erythroblastopenia of childhood

In the period 1975–1983 22 patients, aged 4–36 months were seen with severe transient normochromic, normocytic anaemia caused by a transient erythroblastotopenia.In 20 patients bone marrow aspirations were obtained; they showed erythroblastopenia.In ten cases we observed young lymphoid cells, suggesting a diagnosis of acute lymphoblastic leukaemia. One patient suspected of a leukaemia, was studied in more detail.All patients showed reticulocytopenia. MCV and HbF were within normal range. During recovery reticulocytosis and higher levels of HbF were found. Except for blood transfusion in most patients, therapy (e.g. corticosteroids) was not necesssary. Spontaneous recovery is a feature of this kind of erythroblastopenia, contrasting with congenital hypoplastic anaemia.Abbreviations CHA congenital hypoplastic anaemia - TEC transient erythroblastopenia of childhood - MCV mean corpuscular volume - HbF fetal haemoglobin - ALL acute lymphoblastic leukaemia - cALL common ALL - IgG immunoglobulin G     

Prognostic factors in acute lymphoid leukaemia of childhood. II. Cell surface markers

Monoclonal sera have been used to determine the surface phaenotype of leukaemic cells during the last three years. Bone-marrow specimens of 57 children with recently diagnosed acute lymphoid leukaemia were examined; four cases were classified as T-cell leukaemia, 2 cases as B-cell leukaemia, in 37 cases cALLa was positive and fourteen children were classified as O-cell type, based on the absence of markers. Analysis of symptom-free survival revealed a very poor prognosis in B-cell leukaemia; there was no significant difference between the remaining groups. Within the cALLa positive cases L1 exhibited a markedly more favourable prognosis than L2.     

Unexpected medical coincidences require systematic and careful strategies: an example.

In a cohort of 14 children with identical cardiac xenografts, two boys developed acute myeloid leukaemia 11 and 16 months respectively after the operation. A dedicated working group designed a scheme intending to take care of all aspects of the situation. This article focuses on preferred strategies towards patients, relatives, government, and the media. We did not find any substantial evidence supporting the association between bovine xenografts and two cases of acute myeloid leukaemia.     

Unexpected medical coincidences require systematic and careful strategies: an example

In a cohort of 14 children with identical cardiac xenografts, two boys developed acute myeloid leukaemia 11 and 16 months respectively after the operation. A dedicated working group designed a scheme intending to take care of all aspects of the situation. This article focuses on preferred strategies towards patients, relatives, government, and the media. We did not find any substantial evidence supporting the association between bovine xenografts and two cases of acute myeloid leukaemia.     

Evaluation of risks related to human growth hormone (hGH) treatment. Results of an epidemiologic survey conducted in France of patients treated from 1959 to 1985

Following the notification in the USA and England of four cases of Creutzfeldt-Jacob disease (MCJ) in patients previously treated with hGH, an epidemiological inquiry has been done in France to set up a clinical evaluation of all patients treated from 1959 to 1985. 1698 patients were registered for treatment. Current information (less than three months old) was obtained for 1622 patients (95.5%). Death was reported in 32 patients (2.0%), one is possibly related to a viral infection (malignant lymphoma), but none could be related to MCJ. Accidents were observed in 213 living patients (13.1%). Among them, 4 cases were classified as possibly related to a viral infection: acute lymphoid leukaemia, polyradiculoneuritis associated with hepatitis, acute encephalitis (2 cases). Even though the clinical symptomatology is not consistent with MCJ, a relationship with hGH therapy could not be completely excluded. Finally, six patients undertreatment developed malignancies. During the three last years, the question of side effects of hGH therapy has been raised in the literature two times running: risk of MCJ and risk of leukaemia. Then, the question of the long term vigilance of all treated patients with hGH deficiency should be done.     

Deep Candida infection in children with leukaemia: clinical presentations, diagnosis and outcome

Objectives : To analyse the clinical features associated with deep Candida infection (DCI) and the outcome in children with leukaemia, and to evaluate various diagnostic methods. Materials and methods : Serum samples were analysed to determine Candida IgA, IgM and IgG antibodies and detect free C. albicans glucoprotein antigen and C. enolase antigen in eight children who had nine episodes of DCI and six with suspected DCI. Results : DCI occurred shortly after the leukaemia diagnosis (median 40 days) or after the leukaemia relapse (median 30 days). Children with DCI had fever (100%), skin lesions/exanthema (45%), oral thrush (45%), oesophagitis (22%) and laryngo-tracheitis (22%). Candida endocarditis, arthritis and hepatic candidosis were diagnosed in one patient each. Two children with disseminated candidosis died in leukaemia relapse. In patients with C. albicans infections serology had a sensitivity of 83%. However, in patients with C. parapsilosis infection antibody detection was negative. As the patients were cured of their Candida infection, the IgG antibodies disappeared and the IgM and IgA antibodies fell within the normal range for age. Conclusion : DCI in children occurs shortly after the leukaemia diagnosis or shortly after relapse of leukaemia. The clinical features are many. Candida serology may help to diagnose or confirm DCI. The dynamics of antibody titres may help to establish the efficacy of antifungal treatment.     

Helicobacter pylori as cause of gastrointestinal disease in children with hemato-oncologic diseases

After documentation of a case of life threatening Helicobacter pylori (H. pylori) gastric ulcer in an adolescent girl on treatment for acute lymphoblastic leukaemia, we started to systematically look for gastro-intestinal symptoms due to H. pylori infection in our cancer patients at G. Gaslini Children's Hospital. During a period of 46 months, we observed 13 further cases of severe dyspepsia syndrome or gastro intestinal bleeding associated with presence of H. pylori faecal antigen. All patients recovered with appropriate therapy. H. pylori may represent a cause of severe gastrointestinal complications in children with cancer or following bone marrow transplant.     

Prognosis of Down's syndrome with acute leukaemia.

The outcome in children with acute leukaemia with (n = 90) and without Down''s syndrome (n = 4377) was compared. Sixty three (70%) of those with Down''s syndrome had acute lymphoblastic leukaemia and in comparison with 3664 (84%) controls had similar prognostic features except for a significant excess of the ''common'' immunological subtype of acute lymphoblastic leukaemia. The outcome of the children with Down''s syndrome was significantly worse with a five year overall actuarial survival of 28% compared with 59% in the control group. It appeared that both suboptimal chemotherapy and a high rate of infective problems contributed to the poor survival. Twenty six children with Down''s syndrome had acute myeloblastic leukaemia and were significantly younger and had a higher percentage of the megakaryocytic and erythroid subtypes of acute myeloblastic leukaemia than the 713 controls. The outcome was similar in the two groups. It is concluded that the patients with Down''s syndrome who develop acute leukaemia should receive standard protocols without modification, but aggressive supportive care is necessary to improve outcome.     

Bone marrow fibrosis and radiological changes of the long bones in children with acute megakaryocytic leukaemia

The diagnosis of acute megakaryocytic leukaemia (AMkL) may be difficult to establish owing to difficulties in obtaining adequate bone marrow aspirates secondary to bone marrow fibrosis. We describe three children without Down's syndrome under 2 y of age with AMkL. Although none of the patients had the non-random t (1;22) (p13;q13) translocation, bone marrow cells from all patients exhibited chromosome abnormalities with complex karyotypes, including trisomy 21 in two cases. All patients had profound bone marrow fibrosis and characteristic lamellar diaphyseal radiological changes of the long bones.     

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia

OBJECTIVE: To correlate clinical presentation and therapeutic outcomes in children with a diagnosis of juvenile myelomonocytic leukaemia. METHODS: The medical records of 14 children who fulfilled the International Juvenile Myelomonocytic Leukaemia Working Group Criteria for a diagnosis of juvenile myelomonocytic leukaemia (JMML) presenting to a single institution were reviewed, and their clinical status at September 2000 was documented. RESULTS: The most common presenting features were hepatosplenomegaly and lymphadenopathy. Fifty per cent of cases presented in the first year of life. Nine of 14 patients initially received chemotherapy otherwise used in the treatment of acute myeloid or lymphoblastic leukaemia with no apparent benefit. All six patients who received conditioning therapy with chemotherapy alone, followed by allogeneic bone marrow transplant (BMT), are in complete remission at a median follow-up duration of 12 months (range 5-91 months). Five of six patients surviving post-allogeneic BMT received marrow from an unrelated donor. Only one of seven patients who did not receive BMT survived long-term. CONCLUSION: Children with a diagnosis of JMML should be treated with allogeneic BMT as soon as a suitable donor is found. The role of anti-leukaemic therapy in this disease, prior to BMT, requires further investigation in the context of a multicentre clinical trial.     

Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients

A total of 203 paediatric cancer treatment survivors were tested for serum antibodies against hepatitis-C virus (anti-HCV). Anti-HCV was detected in 41 patients (20.2%) with first generation anti-HCV ELISA. Positive results were confirmed in all samples retested with a second generation ELISA (n=35) and in all but two cases re-analysed by immunoblotting (n=23). Anti-HCV positive children had received significantly more blood product transfusions compared to seronegative patients. In 75 children (32%) chronic liver disease was found. It was defined as an elevation of serum alanine aminotransferase values to a least 2.5 times the upper limit of normal persisting for 6 months or longer. Hepatitis A was never detected, and in 58 children the chronic hepatopathy was unexplained by hepatitits B (non-A non-B chronic liver disease). Of these patients 29 (50%) were seropositive for anti-HCV. Surprisingly, non-A/non-B chronic liver disease was associated with anti-HCV in 14 of 19 solid tumour patients (78.9%), but in no more than 14 of 39 leukaemia and lymphoma patients (35.9%). This phenomenon was not explained by different rates of cytomegalovirus disease and drug toxicity related hepatopathies between the two groups. It may be related to differences of leukaemia/lymphoma compared to solid tumour therapy schedules (differential immuno-suppression and liver toxicity).     

Lymphocyte markers in childhood ALL: the lack of correlation with prognosis

Presentation blast cells from 39 children with acute lymphoblastic leukaemia were studied for T- or B-lymphocyte characteristics. Eleven patients had blasts with T-cell phenotype and one child had B-cell leukaemia. The rest belonged to the non-T, non-B group. Clinical features were similar in the T-cell and non-T, non-B cell group, including the initial WBC count and the presence of mediastinal mass. Although patients with T-cell leukaemia fared worse than those in the non-T, non-B group, the difference in survival was not statistically significant. These data are not in accordance with the findings of most other groups and are thought to stem from the chance occurrence of relatively low initial WBC counts in the T-cell group.     

Prevalence of multi‐drug resistant organisms in stool of paediatric patients with acute leukaemia and correlation with blood culture positivity: A single institution experience

1 Background

Multi‐drug resistant (MDR) bacteria are associated with increased morbidity and mortality in children with acute leukaemia. The present study was conducted to assess the prevalence of MDR bacteria in stool cultures of patients with acute leukaemia at presentation to the hospital. The results were then correlated with blood cultures when patients developed septicaemia.

2 Patients and methods

The study involved analysis of case records of patients with newly diagnosed acute leukaemia less than 18 years of age treated at our centre from January 2015 to December 2015. Stool cultures were sent within 72 hr of hospital admission and blood cultures were sent when clinically indicated. MDR was defined as resistance to at least one antibiotic in three or more following antimicrobial groups: cephalosporins, β‐lactam/β‐lactamase inhibitor, carbapenems, fluoroquinolones and aminoglycosides.

3 Results

The analysis included 85 patients with acute leukaemia, among whom 48 of 85 (56%) patients had positive stool cultures and 42 of 85 (50%) patients were positive for MDR bacteria. Blood cultures were positive in 13 of 48 patients (27%, seven MDR and six non‐MDR) with positive stool cultures and three of 37 patients (8%, one MDR and two non‐MDR) with negative stool cultures (P = 0.01). The concordance between stool and blood culture for similar organism was 61%. There were seven deaths in 48 stool culture positive patients and two deaths in 37 stool culture negative patients.

4 Conclusion

This study shows the high prevalence of MDR bacteria in newly diagnosed children with acute leukaemia. Colonisation with MDR bacteria in stools is associated with increased positivity of blood cultures and mortality.