Feasibility of psychoeducational interventions in managing chemotherapy-associated nausea and vomiting (CANV) in pediatric oncology patients.

PURPOSE: Childhood cancer patients often suffer from Chemotheraphy-Associated Nausea and Vomiting (CANV). To alleviate CANV, relaxation techniques and patient education were combined to develop a multidimensional psychoeducational intervention package. The aim of this pilot study was to assess the feasibility of the two major components, namely, (1) relaxation, and (2) patient education, of a psychoeducational intervention, prior to the commencement of the main study. METHODS: A pre-test-post-test control group design was adopted. Twenty patients were allocated equally to the relaxation group (10 participants) and to the educational group (10 participants). Twenty historical matched control cases were identified to form the control groups. Besides, a process evaluation was adopted to assess the feasibility of the study. RESULTS: In relation to episodes of vomiting on day 3, a significant difference was detected from the results (X(2) = 8.54, p = 0.036), in that fewer patients in the relaxation group experienced vomiting. A significant difference was not found in both the use of antiemetics and body weight between the groups. All subjects in the intervention groups adhered to the intervention and completed the questionnaire without difficulty. Patients and parents perceived the intervention as being moderately useful. CONCLUSIONS: Although the beneficial effect of relaxation and education in alleviating CANV was not well-supported statistically, the findings from descriptive data suggest that these interventions promoted the intake of antiemetics as a preventive method. Both interventions and instruments were well-received by the patients and also by their parents.

Humoral immune response after post-chemotherapy booster diphtheria-tetanus-pertussis vaccine in pediatric oncology patients.

BACKGROUND: The role of post-chemotherapy booster vaccination in pediatric oncology children remains to be established. In this randomized controlled study, we studied the effect of immune responses to diphtheria-tetanus-pertussis (DTP) booster vaccination in children 6 months after completing chemotherapy. METHODS: Children 1-18 years old with chemotherapy completed for 6 months (baseline) were eligible. Subjects were randomized into vaccine and control group. In the former, three doses of DTP vaccine (Aventis Pasteur Inc., Lyon, France) were administered. IgG antibody titers against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps, and rubella antibodies were measured serially in vaccine and control groups. Subsets of circulating lymphocytes (CD3(+), CD4(+), CD8(+), CD19(+), and CD16/56(+)) were quantified by flow cytometry using fluorescence-labeled monoclonal antibodies. RESULTS: Fifty-six children (28 vaccinees; 28 controls) were enrolled. Protective antibody levels against diphtheria, tetanus, pertussis were found at baseline in 83.6%, 96.5%, 96.1% of them respectively. After three doses of DTP, all vaccinees demonstrated a sustain rise in antibody levels and the antibody titers were significantly higher than control group. 35.8% of subjects were susceptible to measles mumps and rubella infection and 69% showed anti-HBs antibody titer less than protective level up to 18 months after stopping chemotherapy. CONCLUSIONS: Post-chemotherapy booster vaccinations produced a strong and sustained effect in humoral immunity against vaccine-preventable infectious diseases.

Clonal evolution of 8p11 stem cell syndrome in a 14-year-old Chinese boy: a review of literature of t(8;13) associated myeloproliferative diseases.

We describe a case of coexisting BCR-ABL negative myeloproliferative disorder and precursor T-cell lymphoblastic lymphoma associated with t(8;13) involving FGFR1 at 8p11 in a 14-year-old boy who presented with generalized lymphadenopathy and an abdominal mass. JAK2 mutation and FIP1L1-PDGFRalpha were not detected. RT-PCR revealed the ZNF198-FGFR1 fusion transcript in both the bone marrow (BM) and lymph node (LN) of the patient at diagnosis. Of interest, reciprocal FGFR1-ZNF198 fusion transcript was demonstrated in the BM but not LN. Also differential clonal TcRgamma gene rearrangements in the BM and LN samples were observed. These findings provide novel insights into the genetic pathogenesis.

A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassemia major patients from Hong Kong.

A controlled, open-label and randomized study was conducted to evaluate the safety and efficacy of the oral iron chelator deferiprone (L1) in thalassemia major patients from Hong Kong. Forty-nine patients were recruited in total (median age: 20 years; range: 8 to 40 years). The division of the patients was determined based on liver iron content and put into either the poorly-chelated (Group I) or well-chelated (Group II) groups. In Group I, 20 patients received combined therapy of L1 daily plus desferrioxamine (DFO), in a reduced frequency of twice weekly, while the control group consisted of 16 patients who were treated with DFO alone. In Group II, six patients received L1 only, while the control group consisted of seven patients treated with DFO alone. Only patients who participated for longer than 6 months were analyzed for efficacy (n = 44). The median study period was 18 months. Transient and mild gastrointestinal upset (31%), joint pain (15%) and liver enzyme elevation (23%) were the most common side effects noted for L1. No case of neutropenia was observed in this study. Serum ferritin (SF) levels showed significant decline in the poorly-chelated patients using combined therapy (L1 and reduced frequency DFO) as compared to those on DFO alone. However, their pre- and post-study liver iron content was not significantly different. Evaluation of the well-chelated group demonstrated no significant change in SF or liver iron content in both the study and control arms. We conclude that the short-term use of L1, with or without DFO, was safe and efficacious in our Chinese patient cohort. The long-term efficacy of reducing iron overload by treatment regimens including L1 requires further study.

Autoimmune hypothyroidism after unrelated haematopoietic stem cell transplantation in children.

We describe two pediatric patients who developed autoimmune hypothyroidism 2 years after unrelated allogeneic hematopoietic stem cell transplantation. The causes of post-transplantation autoimmune hypothyroidism are probably multiple. In these two patients, the presence of chronic graft-versus-host disease may be the most significant contributing factor.

A malignant itch.

We report an unusual presentation of a previously healthy three-year-old Chinese girl with a four-week history of apparently unexplained generalized intense itch. She had no past history of atopy or xerosis. Despite the severe itch, she had only minimal scratch marks on her right gluteal region but no flexural involvement. The girl was treated as having scabies and eczema and with oral antihistamines by various dermatologists without much improvement. She subsequently presented to a regional hospital with right hip pain and fever. Radiological and histopathological investigations confirmed that she had a peripheral T-cell lymphoma. The itch pattern prior to and following chemotherapy, as documented by the DigiTrac wrist-held movement monitor, showed a dramatic reduction of her nocturnal itch. The pattern was also very different from that of atopic dermatitis in that the scratching was of much higher intensity but lower frequency. Intractable pruritus associated with a peripheral T-cell lymphoma has not been previously reported in the pediatric literature. This report serves to alert clinicians of the gold paradigm that in a patient with an unexplained generalized itch, lymphoma and other malignancies must be considered.

Critical airway obstruction, superior vena cava syndrome, and spontaneous cardiac arrest in a child with acute leukemia.

We report the unusual presentation of a previously healthy girl with sudden cardiopulmonary arrest caused by acute lymphoblastic leukemia and mediastinal involvement leading to acute tracheal and airway obstruction. Despite active resuscitation and mechanical ventilation, she developed severe cerebral edema as a result of cerebral asphyxia. She also had facial edema caused by superior vena cava obstruction, a high peripheral white cell count with blast differentials, and renal failure. Because of severe asphyxia leading to brain death and renal failure, chemotherapy was withheld. Her white cell count spontaneously reverted to reference range without chemotherapy. This report serves to alert clinicians of the oncological emergency of "superior mediastinal syndrome" causing airway and superior vena cava obstruction leading to death in this potentially curable disease.

Partial neuroprotective effect of pretreatment with tanshinone IIA on neonatal hypoxia-ischemia brain damage.

Tanshinone IIA is a compound purified from the Chinese herb Danshen (Radix Salviae Miltiorrhiza Bge). The neuroprotective effect of tanshinone IIA was investigated in a neonatal rat model of hypoxia-ischemia brain damage. Hypoxia-ischemia encephalopathy was induced in rats at day 7 of postnatal age by ligation of the right common carotid artery, followed by 2 h of hypoxia. Tanshinone IIA (10 mg/kg, i.p.) was injected daily from day 2 before surgery for 9 or 16 d. Our results demonstrated significant and sustained brain damage in the hypoxia-ischemia- and vehicle-treated groups at 1 and 3 wk after surgery. Treatment with tanshinone IIA significantly reduced the severity of brain injury, as indicated by the increase in ipsilateral brain weight and neuron density, compared with those of sham-operated animals. The recovery of sensorimotor function and histology was observed in animals that received tanshinone IIA. The plasma of tanshinone IIA-treated rats exhibited higher antioxidant activities, as reflected by the oxygen radical absorbance capacity assay, compared with the vehicle-treated rats. In the neural progenitor cell line C17.2 that was subjected to 2,2'-azobis (2-amidino propane hydrochloride)-induced oxidative stress, tanshinone IIA increased cell viability and protected against mitochondrial damage (JC-1 assay). Our results suggest that tanshinone IIA has antioxidative activities and that treatment that is started before a hypoxic-ischemic insult is partially neuroprotective. Further studies are required to elucidate whether rescue treatment with tanshinone IIA is effective and to determine whether its protective effect is also associated with secondary cooling of the brain.

Arsenic trioxide mediates intrinsic and extrinsic pathways of apoptosis and cell cycle arrest in acute megakaryocytic leukemia.

Arsenic trioxide (ATO) induces apoptosis in a range of solid tumors and leukemia cells, and has been clinically applied for the treatment of acute promyelocytic leukemia with confirmed efficacy. Acute megakaryocytic leukemia (AMKL) is an aggressive malignancy with poor prognosis, if bone marrow transplantation is not possible. In this study, we applied flow cytometry, Western blot analysis and microarray techniques to investigate the effects of ATO on apoptosis and the cell division cycle of AMKL cell lines CHRF-288-11 and MEG-01. Our data demonstrated that ATO is a potent agent against AMKL as indicated by apoptotic markers, Annexin V and caspase-3. ATO activated the intrinsic (mitochondrial) pathway of apoptosis, which involved disrupting mitochondrial membrane potential, increased Bax/Bcl-2 ratio and caspase-9 activation, as well as the extrinsic (death receptor) pathway mediated by Fas and caspase-8 activation. We provided the first evidence that ATO stimulated expressions of CD137 mRNA and protein, which might be relevant to the extrinsic mechanism. ATO induced delays of cell cycle progression at S phase and arrest at G2/M phase of AMKL cells, but caspase-3 expression appeared not to be phase-specific. The multiple-signaling mechanism of ATO warrants it a potential agent to incorporate in the treatment regimen of AMKL.

Liver volume in thalassaemia major: relationship with body weight, serum ferritin, and liver function.

BACKGROUND: It is not known whether body weight alone can adjust for the volume of liver in the calculation of the chelating dose in beta-thalassaemia major patients, who frequently have iron overload and hepatitis. OBJECTIVE: The hypothesis is that liver volume in children and adolescents suffering from beta-thalassaemia major is affected by ferritin level and liver function. MATERIALS AND METHODS: Thirty-five beta-thalassaemia major patients aged 7-18 years and 35 age- and sex-matched controls had liver volume measured by MRI. Serum alanine aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia major patients. RESULTS: Body weight explained 65 and 86% of the change in liver volume in beta-thalassaemia major patients and age-matched control subjects, respectively. Liver volume/kilogram body weight was significantly higher (P < 0.001) in thalassaemia major patients than in control subjects. There was a significant correlation between ALT level and liver volume/kilogram body weight (r = 0.55, P = 0.001). Patients with elevated ALT had significantly higher liver volume/kilogram body weight (mean 42.9 +/- 12 cm3/kg) than control subjects (mean 23.4 +/- 3.6 cm3/kg) and patients with normal ALT levels (mean 27.4 +/- 3.6 cm3/kg). CONCLUSIONS: Body weight is the most important single factor for liver-volume changes in thalassaemia major patients, but elevated ALT also has a significant role. Direct liver volume measurement for chelation dose adjustment may be advantageous in patients with elevated ALT.

Identification of TPO receptors on central nervous system-a preliminary report.

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.

Growth and endocrine function following bone marrow transplantation for thalassemia major.

Thalassemia major (TM) patients frequently suffer from growth delay and endocrine dysfunction. Thirty-two TM patients who had survived more than 2 years after bone marrow transplantation (BMT) were recruited for growth and endocrine study. Patients were followed up annually for growth, and the height was expressed as height standard deviation score (HtSDS). The HtSDS at baseline was -1.51 and was more reduced in patients older than 7 years (-1.99) as compared with those younger patients (-0.79) (p =.027). The HtSDS gradually improved after BMT and increased by 0.59 (CI 0.16-1.01) at 5 years after BMT. Forty percent of patients were below 2 SD at time of BMT but this decreased to 15% at the latest assessment. The hormonal profiles of gonadotrophins, sex hormones, and thyroid function were assayed regularly after BMT. With a median follow-up of 67 months, ovarian failure was universal among the 10 girls evaluable for puberty and all required hormonal replacement. Eight of 10 boys had spontaneous puberty but 3 of them had gonadal impairment. One patient developed diabetes mellitus and one had growth hormone deficiency after BMT. In conclusion, improvement of growth after BMT in TM was common. Gonadal failure is universal in girls, and boys were less affected.

Immunogenicity of a two-dose regime of varicella vaccine in children with cancers.

OBJECTIVE: Live-attenuated varicella vaccine is effective and safe in immunocompetent children. In this study, we assess the immunogenicity and adverse events following varicella vaccination in immunosuppressed cancer children. METHODS: Varicella-zoster virus (VZV)-seronegative cancer children received two doses of live-attenuated VZV vaccine (Varilrix) in a span of 3 months. Patients with acute lymphoblastic leukaemia (ALL) were in the maintenance phase of chemotherapy, whereas those with solid tumours joined the study around 3-6 months from treatment discontinuation. VZV-specific cellular and humoral immune responses were measured before and after VZV vaccination. RESULTS: The median (range) age of the 17 patients was 4.4 yr (2.0-14.5). Thirteen had ALL, one had myelodysplastic syndrome and three had solid tumours. Following vaccination, the VZV-specific stimulation index (SI) increased from 1.7 (0.9-2.9) to 17.9 (5.9-36.0) (P < 0.001). Similarly, SI to phytohaemagglutinin mitogen increased from 1136 (499-1930) to 1714 (848-2518) (P = 0.028). There were also significant increases in CD4+ cells and CD4:CD8 ratio as well as a reduction in CD16/56+ cells in peripheral blood lymphocytes. Seroconversion rate to VZV was 19% after one dose and increased to 94% after the second dose of VZV vaccine. Serum VZV-specific IgG concentrations also increased significantly following two doses when compared with one dose of VZV vaccine (P = 0.0004). One subject developed possibly vaccine-related chickenpox with self-limiting hepatitis at 5 wk following vaccination. None of the patients developed herpes-zoster at a median (range) follow-up of 27.5 months (24.0-30.0). CONCLUSIONS: Non-immune cancer children can be effectively vaccinated against chickenpox at the defined period. However, the safety of chickenpox vaccine in these immunosuppressed children needs to be further studied.

Intraocular pressure profile of a child on a systemic corticosteroid.

PURPOSE: To report the ocular hypertensive response to high-dose systemic corticosteroid in a pediatric patient. DESIGN: Observational case report. METHODS: A 9-year-old patient with leukemia received oral prednisolone at a dosage of 2.3 mg/kg/d for 5 weeks, followed by a 4-month break and then a 4-week course of oral dexamethasone at 10 mg/d. Detailed ocular examination was performed for both eyes before and regularly throughout the two courses of treatment. RESULTS: The intraocular pressure in both eyes rose to almost 40 mm Hg after only 8 days of oral corticosteroid. On stopping systemic corticosteroid, the intraocular pressure rapidly returned to baseline level within 2 days. A similar intraocular pressure profile was recorded for both eyes during the course of oral dexamethasone. The patient remained largely asymptomatic throughout. CONCLUSIONS: Systemic corticosteroid may give rise to significant but asymptomatic ocular hypertension in pediatric patients.

Elevated serum interleukin-15 level in acute graft-versus-host disease after hematopoietic cell transplantation.

OBJECTIVE: To correlate serum cytokine levels and the development of acute graft-versus-host disease (GVHD), the authors conducted a prospective study on serial measurements of interferon (IFN)-gamma and interleukin (IL)-10, IL-12 and IL-15. METHODS: The cytokines were measured in 27 subjects by enzyme-linked immunosorbent assay serially for the first 2 months after hematopoietic cell transplantation. RESULTS: Nineteen subjects with acute GVHD had significantly higher mean peak serum levels of IFN-gamma and IL-15 than the baseline levels at the start of conditioning. The peak level occurred soon after stem cell infusion and returned to the pretransplantation state in the second month. In contrast, there was lesser difference between the mean peak serum levels of IFN-gamma, IL-10, and IL-15 and the baseline level in the eight subjects without GVHD. The peak serum level for IL-15 was, in addition, significantly higher among GVHD subjects than those without GVHD in the first month posttransplantation. However, the level of IL-15 showed no correlation with the severity of GVHD. CONCLUSIONS: These changes point to a possible role of systemic cytokine secretion in the development of acute GVHD. Elevated levels of IL-15 early in the posttransplant period could be a helpful laboratory predictor of acute GVHD.

Thrombospondin-1 induces apoptosis in primary leukemia and cell lines mediated by CD36 and Caspase-3.

Thrombospondin-1 (TSP-1) is a naturally occurring anti-angiogenic compound that induces apoptosis of endothelial and cancer cells via its receptor CD36. The objectives of our study were to investigate the in vitro effects of TSP-1 on the apoptosis of primary human leukemia cells as well as leukemia cell lines and the possible mechanism involving CD36. Our results demonstrated that TSP-1 induced apoptosis in CD36 positive cell lines CHRF-288-11, Meg-01 and HL-60, but not CD36 negative K562, at a dose-dependent manner as demonstrated by DNA ladder formation, Annexin V and propidium iodide (PI) stainings. The addition of anti-CD36 antibody FA6-152 or thrombopoietin (TPO) significantly nullified the effects of TSP-1. TSP-1-mediated apoptosis was consistently associated with the up-regulation of active Caspase-3. Responses of 2 CD36 positive primary AML samples to TSP-1 and FA6-152 were similar with those of leukemia cell lines. TSP-1 significantly induced apoptosis in B-ALL but the counter-effects of FA6-152 were less apparent. CD36 negative AML cells appeared less susceptible to TSP-1 and FA6-152. Our data provided strong evidence that TSP-1 exerted direct apoptotic effects on leukemia cells and could be developed as an adjunct to conventional therapy, particularly for leukemia cells that express CD36 or other TSP-1 receptors.

White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR spectroscopy.

PURPOSE: To assess the development of white matter and cerebral metabolite changes during and after treatment in children with acute lymphoblastic leukemia. MATERIALS AND METHODS: Twenty-three children (10 boys, mean age of 6.3 years; 13 girls, mean age of 6.6 years) with acute lymphoblastic leukemia were examined prospectively with magnetic resonance (MR) imaging and MR spectroscopy at 0, 8, and 20 weeks and 1, 2, and 3 years after diagnosis. White matter changes were diagnosed on the basis of hyperintense abnormalities on T2-weighted MR images. Single-voxel hydrogen 1 MR spectroscopy results from the right frontoparietal region of 21 children who received intravenous high-dose methotrexate were analyzed for cerebral metabolite changes. Multilevel models were used to assess the change in metabolites from baseline levels at subsequent follow-up. RESULTS: At 20 weeks, MR spectroscopy showed a significant reduction (P <.05) of mean N-acetylaspartate to choline ratio and increase in mean choline to creatine ratio (P <.05) in the children given high-dose methotrexate. This decline in N-acetylaspartate to choline ratio subsequently reversed and increased, possibly because of normal age-related brain maturation. Seventeen of 21 (81%) children showed metabolite changes at MR spectroscopy, while five of 22 (23%) showed white matter changes at MR imaging at 20 weeks. One more child developed white matter changes at 32 weeks. The associated changes resolved or reduced with time. CONCLUSION: MR spectroscopy demonstrated metabolite changes in the brain after high-dose methotrexate treatment in the absence of structural white matter abnormalities at MR imaging. MR spectroscopy might thus be a more sensitive method of monitoring the effects of high-dose methotrexate in the brain.

Genetic variation of glycoproteins B and H of human herpesvirus 7 in Hong Kong.

Glycoprotein B (gB) and glycoprotein H (gH) of human herpesvirus 7 (HHV-7) are believed to play an important role in virus entry and as targets for host immune response. This study examined the genetic diversity of these glycoproteins among 90 HHV-7 isolates collected from different individuals in Hong Kong. Overall, both the gB and gH genes were found to be highly conserved. Nucleotide polymorphism was detected only at four positions of the gB-encoding region, and all of these were synonymous substitutions. Most (97.8%) Hong Kong isolates were of gB allele group C. Two isolates collected from a Pakistani family showed a novel sequence pattern that did not match known gB allele groups. This sequence pattern was detected consistently from serial samples collected from the same individual, indicating a stable genetic entity. The gH-encoding region exhibited nucleotide polymorphism at six positions. Three of these were nonsynonymous substitutions (codon 271 Lys --> Gln, codon 308 Gly --> Glu, codon 397 Asn --> Tyr). Most (84.4%) Hong Kong isolates were of the gH allele group B, and all others were of the gH allele group C. These data indicate the possibility of using gB or gH alleles as markers for studying world-wide population movements and genetics.