Immune thrombocytopenia following successful treatment of cancer in children

A predisposition to developing immune thrombocytopenia (ITP) has not been reported in survivors of childhood cancer. We report a case series of childhood cancer survivors who developed an isolated thrombocytopenia in the presence of a normocellular bone marrow. Five children, two with endodermal sinus tumors and three with acute lymphoblastic leukemia, developed ITP at a median of 4 years (range: 0.2-8 years) after completion of therapy. We suggest the association of ITP in survivors of childhood malignancy may not be co-incidental as chemotherapy may cause persistent immune dysfunction.     

Immune function in children with classical phenylketonuria and tetrahydrobiopterin deficiencies

BACKGROUND: An increased susceptibility to infections has been observed in some patients with phenylketonuria (PKU), which is not well known whether it is due to alterations of plasma essential amino acid concentrations or to some other factors. OBJECTIVE: This study is designed to establish B cell and T cell functions in 44 children with classical PKU and tetrahydrobiopterin (BH4) deficiencies and the effects of too high plasma phenylalanine (PA) concentrations (16.53 to 30.54 mg/dL) on the same parameters. DESIGN: B and T cell functions of 33 children with classical PKU (divided into two groups based on fasting mean plasma PA concentrations: Group-I = 20.9 +/- 3.7 mg/dL, Group-II = 3.8 +/- 1.02 mg/dL), and 11 children with BH4 deficiencies (Group III) were studied. The results were compared between the groups and referenced with previously reported values from healthy controls. RESULT: Delayed type skin hypersensitivity responses to purified protein derivative (PPD) in Group I and phytohaemagglutinin (PHA) in Group I, III were lower than the other groups and healthy controls. Plasma IgG and IgM concentrations of Group I was lower than the reference values. Although mean serum zinc and iron levels of all patients were lower than published values of healthy children, zinc and iron deficiencies in Group I, III were much more prominent as compared to Group II. CONCLUSION: The somewhat low plasma IgG concentrations in Group I may be related to the very high plasma PA levels, however the role of zinc deficiency as a causal factor can not be ruled out. BH4 metabolism defects do not appear to affect the same parameters. Impaired delayed skin hypersensitivity responses in Group I and III can be explained by severe serum zinc deficiency. In the light of this study, we conclude that in order to establish a causal relationship between PKU and immune functions, further studies need to be conducted after the correction of micro-nutrient status of such children.     

Immune deficiencies in chronic intestinal pseudo-obstruction

Aim: Chronic intestinal pseudo-obstruction has been associated with urinary disorders, myopathy, and ophthalmoplegia in adults and cholelithiasis in children. We observed a high percentage of total-parenteral-nutrition-dependent patients with pseudo-obstruction and recurrent infections requiring gammaglobulin infusions. Methods: AH records for 23 children with chronic intestinal pseudo-obstruction (10 females and 13 males, mean age 9.8 y ± 4.9 y, range 4–24 y) referred for a nutritional evaluation from 1992 to 1995 were reviewed. Chronic intestinal pseudo-obstruction was diagnosed by clinical, radiographic findings and antroduodenal manometry. Intestinal full-thickness biopsies were performed in seven children. Results: Hypogammaglobulinemia was diagnosed in 18 patients (78%): 16 patients had various immunoglobulin deficiencies and 2 had selective antibody deficiency. Intravenous gammaglobulin was administered in 14 patients. Other medical conditions affecting the children are summarized as follows: autonomic dysfunction in 10 patients (43%), recurrent hypoglycemia in 9 (39%), asthma in 9 (39%), cholecystitis in 7 (30%), low serum carnitine level in 6 (26%), urinary dysfunction in 6 (26%), pancreatitis in 5 (22%), behavioral problems in 5 (22%), myopathy in 2 (9%), idiopathic thrombocytopenia in 2 (8%), velopharyngeal insufficiency in 1 (4%), oculocutaneous albinism in 1 (4%), Pierre-Robin syndrome in 1 (4%), and protein C deficiency in 1 (4%). Munchausen syndrome was suspected in two patients. Conclusions: Chronic intestinal pseudo-obstruction appears to be associated with immune deficiencies. It is unclear if the immune deficiencies, intestinal pseudo-obstruction, and the other medical conditions have a common underlying etiology. Repeated infections may be due to impaired immune function in children with chronic intestinal pseudo-obstruction. We recommend screening for immune deficiencies in children with chronic intestinal pseudo-obstruction.     

Immune deficiencies secondary to enzymopathies

Immune deficiencies secondary to enzyme deficiencies that affect purine and pyrimidine metabolism account for approximately 50% of severe immune deficiencies inherited as a recessive autosomal trait. Adenosine deaminase (ADA) deficiency is the most common and also the earliest and most severe of these diseases. ADA deficiency is responsible for a severe combined immune deficiency with alymphocytosis and often characteristic bone and cartilage abnormalities. The treatment of choice is transplantation of compatible bone marrow; in cases where this has not been feasible, replacement therapy with the enzyme coupled to polyethylene glycol has yielded promising results. Purine nucleoside phosphorylase (PNP) deficiency is responsible for an isolated T cell defect. Low serum uric acid levels are highly suggestive of PNP deficiency. Bone marrow transplantation is indicated. In both diseases, the immune deficiency is due to the toxic effect of purine deoxynucleosides on lymphoid cells. Enzyme deficiencies that directly or indirectly affect pyrimidine metabolism (orotate phosphoribosyltransferase and methionine synthase deficiencies) are exceedingly rare and only inconsistently produce an immune defect (involving T cells).     

Ocular deficiencies in deaf children

In a sample of 150 deaf children, 45.3% were found to present ocular anomalies interfering with good vision. This high frequency of visual impairment contributes to the low-level functioning and lack of normal developmental drives characteristic of deaf children. Early identification, competent diagnosis and appropriate intervention by a team of specialists are required in the treatment of such cases.     

Radial longitudinal deficiencies in children

Radial longitudinal deficiencies pose a unique challenge in children’s orthopaedic surgery: a deformity at birth that can be the only visible sign of serious underlying health conditions. Treatment can be intensive and prolonged but children often cope extremely well with compensations for reduced upper limb function. The aim of this article is to describe essential knowledge of the condition, its associations and treatments. We provide a clinical and diagnostic framework to enable appropriate and timely investigations, management and referral where appropriate.     

Nutrient deficiencies in tube-fed children

The charts of children with gastrostomy or jejunostomy tubes followed in the Tube Feeding Clinic at the Children's Hospital of Wisconsin from January 1999 to June 2002 were reviewed. Prevalence of selected nutrient deficiencies were determined and their association with growth and caloric intake was measured. One hundred fifty patients (60% male) met the inclusion criteria. The mean age of children was 7 years 6 months (SD +/- 5 years 4 months). As a proportion of total caloric intake, the mean percentage of calories from formula was 92% (+/- 15). No deficiencies of vitamins D or E were found. Ferritin concentration below lower limits of the age-appropriate range of normal (LLN) was found in 30 of 122 (25%) and hemoglobin was below LLN in 12 of 139 (9%). One patient each had vitamin A, calcium, phosphorus, and magnesium serum concentrations below LLN. Below normal serum zinc was found in 43 of 142 (30%). Ninety-one of 134 patients (68%) had below normal selenium levels, and 29 of 126 (23%) had both zinc and selenium deficiency. A significant association was found between percentage of recommended daily allowance (RDA) of calories received and selenium concentration below LLN. Patients with selenium deficiency received a mean of 75% (+/- 21) of the RDA of calories for age, whereas patients without deficiency received a mean of 91% (+/- 19) of the RDA of calories for age (p < 0.0001). There was a negative association between deficiency and weight for age: patients with selenium deficiency were 33% mean weight for age percentile (+/- 30), compared to 21% (+/- 27, p < 0.05) for those without selenium deficiency. There was a negative correlation between the percentage of RDA of calories and height for age, weight for age, and weight for height (p < 0.05).     

Immune response after influenza vaccination in children with cancer

PURPOSE: To assess the immune response to inactivated trivalent split influenza vaccine in children with cancer. PROCEDURES: Forty-four children with various types of malignancies received two doses of influenza vaccine 2-4 weeks apart. Hemagglutinin-inhibition (HI) antibody titers were determined in paired sera obtained just before the first vaccination and 4 weeks after the second vaccination. RESULTS: Influenza vaccine was administered to all children without any serious adverse effects. Protective titer rates (proportion of patients achieving antibody titers > or =40 among those with pre-vaccination titers <40) and response rates (proportion of patients with fourfold or more antibody rise) were 72% and 65% for H1N1, 60% and 40% for H3N2, and 38% and 46% for influenza B, respectively. However, patients on chemotherapy showed a significantly lower immune response to influenza A than those having completed chemotherapy; protection titer rates were 42% versus 90% for H1N1 (P = 0.006) and 25% versus 83% for H3N2 (P = 0.019). For influenza B, patients with low IgG showed a lower response rate than those with high IgG (29% vs. 61%, P = 0.040). Multivariate analysis revealed that factors significantly associated with a lower immune response were low IgG (P < 0.001) and administration of chemotherapy (P = 0.003) for H1N1, administration of chemotherapy (P = 0.008) for H3N2, and low white blood cell (WBC) count (P = 0.030) and low IgG (P = 0.030) for influenza B. CONCLUSIONS: Influenza vaccination given to children with cancer was safe and induced immune reaction comparable to healthy children, although patients on chemotherapy and/or with chemotherapy-related conditions had a limited ability to produce a sufficient immune response.     

Immune granulocytopenia in children

Immune neutropenia in infancy comprises alloimmune neutropenia and autoimmune neutropenia. Both diseases are caused by granulocyte-specific antibodies. Patients are newborns and children, often being younger than three years. Neutropenia usually leads to recurrent mild bacterial infections. Beside the blood count and the bone-marrow smear demonstration of granulocyte-specific antibodies is typical. As neutropenia is self-limiting, most patients require only conservative management. In more severe cases interventions with high-doses of intravenous immunoglobulin or corticoid-therapy are indicated.     

Health-related quality of life in children and emotional reactions of parents following completion of cancer treatment

BACKGROUND: Completing therapy is one of the major transitions in care in the practice of pediatric oncology and, therefore, deserves special consideration. The purpose of the study was to investigate health-related quality of life (HRQOL) of pediatric patients, and emotional reactions of their parents, shortly after the end of successful treatment. METHODS: HRQOL of 126 patients, aged 1-15 years, on average 2 months after the end of successful treatment, was assessed with the TNO-AZL Pre-school Quality of life Questionnaire and the TNO-AZL Children's Quality of life Questionnaire. Emotional adjustment of 124 mothers and 111 fathers was assessed with the General Health Questionnaire and the Situation Specific Emotional Reaction Questionnaire. The outcomes of the patients and parents were compared with norm data by means of one sample t-tests, one sample sign-tests or binomial tests. RESULTS: All age groups, except patients aged 8-11 years, experienced worse HRQOL than the norm with respect to motor functioning. In addition, pre-school patients were rated worse on sleeping, appetite, stomach, skin, problem behavior, anxiety, and liveliness, and patients aged 6-7 years on autonomy and cognitive functioning. Parents reported more psychological distress than the norm. Compared to parents whose children were 1-5 years after cancer treatment, they suffered more from feelings of loneliness, helplessness, and uncertainty. CONCLUSIONS: A few months after the end of successful cancer treatment, both patients and parents appeared to experience worse well-being than the norm to a clinically relevant extent. Supporting patients and parents should not stop when treatment ends.     

IgG subclass deficiencies in children: Facts and fiction

The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey¹. Since then, a lot of new information on the role of subclasses and their deficiency states in humans has been obtained. This review tries to analyse critically our current knowledge of subclass deficiencies in children.     

The treatment of cancer pain in children

In summary, expertise is currently available to successfully manage most pediatric cancer pain; it behooves the responsible physician to be sufficiently familiar with the available methodology and to appropriately deliver state-of-the-art management to the child to ensure optimal care.     

Transient IgG subclass deficiencies in newly diagnosed diabetic children

In 27 children (15 males and 12 females) with insulin-dependent diabetes mellitus (IDDM), aged 1.2–13.5 years (mean 9.9±3.6 years) we investigated immunoglobulins (IgG, IgA, IgM), IgG subclass levels and islet-cell antibodies (ICA) at diagnosis and at 6 and 12 months after disease onset. At diagnosis, IgG levels were lower than-2SD in 7 patients (26%), IgA in 1 (3.7%), IgM in 1 (3.7%). IgG subclass levels were below the 3rd percentile in 13 patients (48.1%); in particular IgG1 in 7 (26%), IgG2 in 3 (11.1%), IgG3 in 2 and IgG4 undetectable in 1 case. In 3 out of the 13 patients combined IgG1-IgG3, IgG1-IgG2 and IgG1-IgG4-IgA deficiencies were observed. ICA were >20 Juvenile Diabetes Foundation units in 17/27 patients. The HLA-DR2 frequency was higher in patients with IgG subclass deficiency than in patients with normal IgG subclass levels. During follow up, IgG levels normalized in 6 patients while IgA and IgM did not change. IgG1 normalized in 5 out of the 7 patients, IgG2 in all patients while IgG3 and IgG4 did not change. One year later ICA were still present in 8/27 patients. The hypogammaglobulinaemia and IgG subclass deficiencies observed in our patients could have either a genetic or an acquired basis.     

儿童慢性特发性血小板减少性紫癜免疫紊乱与治疗

目的探讨儿童慢性特发性血小板减少性紫癜(1TP)自身免疫的病理机制,以及α-2b干扰素的治疗效果。方法慢性ITP组18例,健康儿童17例,均采用流式细胞术检测外周T淋巴细胞亚群,以及免疫荧光抗体双标记法检测单个核细胞内Th1/Th2细胞因子的表达情况;18例慢性ITP病人均给予α-2b干扰素治疗,总疗程3个月。结果儿童慢性ITP患者存在T淋巴细跑表型及功能异常,其外周血CD4+减少,CD8+升高,CD4+/CD8+明显降低;且Th1/Th2功能失衡,是一种Th2优势疾病。本组18例应用α-2b干扰素治疗,其中显效6例,良效4例,进步3例,无效5例。结论儿童ITP是一种自身免疫性疾病,T淋巴细胞表型和功能异常在慢性ITP的发病中起重要作用。α-2b干扰素治疗可使患儿Th1细胞因子产生增加,而Th2细胞因子产生减少,因而抑制B淋巴细胞产生抗血小板抗体;α-2b干扰素价格低廉,毒付作用轻,应用方便,为儿童慢性ITP开辟了另一条治疗途径。     

Geographic mobility following cancer treatment in Yorkshire, UK

Long term cure and maximising reintegration into society are major goals of childhood cancer treatment. Whether reintegration had occurred was assessed using geographic mobility as an objective proxy. Age, sex, and socioeconomic status were identified as being independently associated with mobility whereas diagnosis and relapse were not.