Milena La Spina

Hepatitis B vaccination failure in celiac disease: is there a need to reassess current immunization strategies?

Human leukocyte antigen (HLA) phenotype DQ2 is considered the most important genetic marker for un-responsiveness to hepatitis B vaccine. Since celiac disease (CD) is also strongly associated with the same haplo-type it may be hypothesized that celiac patients are less able to respond to the vaccine. We report a retrospective study on celiac patients vaccinated with three doses of 10 microg at 3, 5 and 11 months of age by an intramuscular injection of a recombinant hepatitis B vaccine (Engerix B). We found 30 of 60 celiac patients (50%) unresponsive to vaccination and a significant higher number of responders among patients younger than 18 months at the time of celiac disease diagnosis. Our study confirms that celiac patients have a lower percentage of response to hepatitis B vaccination than healthy subjects. These findings provide useful information to evaluate if current vaccine strategies should be reassessed and if revaccination should be recommended.

Iron Deficiency Anemia as the Only Sign of Infection with Helicobacter pylori : A Report of 9 Pediatric Cases

Recently, an association betweenHelicobacter pylori (HP) and iron deficiency anemia (IDA) was proposed. We describe 9 pediatric patients with a history of long-standing IDA and HP infection. After HP test results were confirmed to be positive, anti-HP therapy consisting of omeprazole, clarithromycin, and amoxicillin was administered for 2 weeks. The hematologic profile and iron status were assessed before and periodically after the end of the eradication regimen. The eradication of HP was associated with stable normalization of iron stores. HP infection may be involved in cases of IDA of unknown origin, and the eradication of HP is associated with the resolution of anemia.

Hepatitis B Vaccine Administered by Intradermal Route in Patients With Celiac Disease Unresponsive to the Intramuscular Vaccination Schedule: A Pilot Study

Hepatitis B Vaccine Administered by Intradermal Route in Patients With Celiac Disease Unresponsive to the Intramuscular Vaccination Schedule: A Pilot Study

Changes in cytokine profile pre- and post-immunosuppression in acquired aplastic anemia

Some patients with aplastic anemia respond to immunosuppressive therapy. Here the authors compare pre and post-immunosuppressive therapy levels of CD3/interefron-γ secreting cells in responders and non-responders. Cytokine expression assessed by flow cytometry in 53 acquired aplastic anemia patients before and after combined immunosuppression (EBMT WPSAA protocols) showed that CD3+ marrow cells containing TNF-α, IFN-γ and IL4 were similar in subjects with disease at onset (DO) and responsive to treatment who had more CD3+/TNF-α+ and CD 3+/IFN-γ+ cells than normal controls. In vitro block of TNF-α and/or IFN-γ significantly increased BFU-e over baseline in 28 patients. In responsive to treatment patients only TNF-α block significantly incremented colonies over normal controls. Absolute marrow CD3+/TNF-α+ and CD3+/IFN-γ+ cells prospectively tested in a group of 21 subjects declined significantly more in Responders than in Non Responders to immunosuppression at Response Evaluation Time respect to Diagnosis. Both in Responders and in Non Responders these cells remained higher than in normal controls. This study suggests that immunosuppression does not fully clear excess TNF-α and IFN-γ from marrow of patients with good outcome and raises the hypothesis that additional cytokine blockade might be useful in immunosuppression for acquired aplastic anemia.

Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma

BACKGROUND This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.

Mutism after surgical removal of a cerebellar tumor: two case reports.

The authors report two pediatric cases of transient mutism that occurred after surgical removal of a medulloblastoma and a pilocytic astrocytoma of the vermis and discuss the pathophysiology of this syndrome. Transient mutism has been described for the first time quite recently, even in cases where these tumors were also surgically removed before. Perhaps improvement in imaging and in surgical techniques made neurosurgeons more daring and some interventions that were judged impossible are routinely performed today. If this is the case, postoperative transient cerebellar mutism might be considered the price that must be paid in order to cure more patients with cerebellar tumors.

Clinical manifestations and management of four children with Pearson syndrome.

Pearson marrow‐pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non‐hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease.

NEUROLOGICAL COMPLICATIONS DURING TREATMENT OF CHILDHOOD CANCER: Mind Wernicke Encephalopathy

Neurological complications are a not rare event during treatment of childhood cancer. Severe neurological events can be explained by recurrence of disease, chemotherapy toxicity, and other life-threatening causes. We hereby report the case of a 12-year-old boy who was diagnosed for acute myeloid leukemia (FAB M5) with central nervous system (CNS) involvement. Right after administration of the first course of chemotherapy induction according to the AIEOP-LAM 2002–01 protocol, he developed nausea, food refusal, and persistent vomiting, which was strongly resistant to conventional antiemetic therapy. Because of the onset of a grade IV mucositis, he was given a “ready to use” total parenteral nutrition (TPN) formulation, without a multivitamin supplementation. After a 30-day fast, physical examination revealed diplopia, nystagmus, and personality changes; within the following 6 days we observed ptosis and convergent strabismus, auditory hallucinations, right hypoacusia, paralysis of lateral recti muscles, gait disturbances, lethargic speech, and drowsiness.

Use of PEG-interferon alfa-2a plus ribavirin as treatment for chronic HCV hepatitis in a child cured of ALL

To the Editor: The natural history of and the treatment options for chronic hepatitis C (HCV) infection, in longterm leukemia survivors, have not been well characterized. Several reports showed the efficacy of combination therapy with peginterferon (PEG-IFN) alfa-2a and ribavirin in immunocompetent adults with chronic HCV infection [1]. There are no data regarding the use of combination therapy with PEG-IFN in children [2]. We report on the administration of PEG-IFN alfa-2a in combination with ribavirin in a child who had chronic HCV infection acquired during treatment for acute lymphoblastic leukemia (ALL). She was treated for ALL in our institution at the age of 3. She had a 10-years history of high serum alanine aminotransferase concentration. She was subsequently diagnosed with HCV genotype-1b positive chronic active hepatitis. After a year of IFN-alfa administration, at the age of 14, she presented with high levels of both serum alanine aminotransferase concentration and baseline viral load. A percutaneous liver biopsy showed a moderate intralobular inflammation/necrosis. Therefore, according to a recently described treatment tailored for adults [1], we administered 180 mg of PEGIFN alfa-2a subcutaneously once weekly, plus daily ribavirin 1,000 mg for a total of 48 weeks. We adopted this dosage based on the fact that she had almost adult size (height 165 cm; weight 48 kg). The Institutional review board of our center approved this treatment and an informed consent was signed by patient’s parents. We assessed the efficacy of this combination therapy by measuring alanine aminotransferase concentration and by performing both qualitative and quantitative HCV RNA RT-PCR using the Cobas Amplicor HCV Monitor assay (Roche Diagnostics-LA Roche, Ltd., Basel, Switzerland). We evaluated therapy response after 1, 4, 8, 12, 24, and 48 weeks, respectively. We noted a dramatic decrease of serum alanine aminotransferase concentration (from 350 to 35 U/L), correlated with a significant decrement in viral load (from>5,000,000 to 50 IU/L). Although we used an adult dosage, no side effects related to the combination therapy have occurred. Three consecutive qualitative HCV-RNA RT-PCR assays have been performed at 3 and 6 months and 1 year from therapy withdrawal, each demonstrating an undetectable level of viral RNA. Although the implementation of blood donor screening, the prevalence of anti-HCV seropositivity among leukemia survivors is still high [3]. Evidence of progression to liver failure in survivors of pediatric malignancies has been reported [3]. Because their previously immunocompromized status might have promoted more rapid viral replication, increasing the risk for a rapid disease progression, amore aggressive approach regarding the use of antiviral therapy in this population with chronic HCV is needed. Based on our experience, we suggest that administration of PEG-IFN in association with ribavirin should be considered as first line treatment in childrenwith chronic HCV hepatitis who have been previously cured of malignancies.

Rituximab in children with idiopathic thrombocytopenic purpura: does it really work?

Sir: Pusiol et al. [1] describe two paediatric cases of successful use of rituximab in idiopathic thrombocytopenic purpura (ITP). They conclude that controlled clinical trials are needed to evaluate both the efficacy and long-term side-effects of the drug. We strongly agree, since case reports are often anecdotal and describe mainly successful outcomes, whereas negative results are neglected. As a matter of fact, our experience with the use of Rituximab in children with chronic ITP is somewhat disappointing, having had only a transient response in one out of three children (Table 1). None experienced immediate side-effects. All of them showed a transient dramatic decrease of CD20+ cells, while serum Ig levels decreased by 20% at most. As paediatric haematologists we constantly experience the frustration of curing chronic cases of ITP whose condition is poorly controlled by conventional therapy, due to either refractoriness or dependence on high dosages or unacceptable side-effects of the various medicaments. We share with other physicians the need for new effective therapies for such cases. Therefore, we feel that an optimistic attitude is a frequent pitfall in such clinical settings and that only rigorously conducted trials can minimise, to an acceptable level, the inevitable bias due to the interpretation of biological phenomena. Furthermore, clinical trials are mandatory in the paediatric population because the experience obtained with adult patients cannot be transferred ‘‘tout court’’ to children. ITP itself may be a different disease in children and adults and the whole pharmacological behaviour may differ greatly in various age groups.