Analysis of factors affecting immune recovery and initial response to tetanus after DTaP vaccination in pediatric allogeneic HSCT patients.

Transfer of donor immunity after allo-HSCT is limited, requiring re-vaccination after HSCT. The CDC 2009 guidelines introduced earlier vaccination post-HSCT with a uniform vaccination strategy. This study objective was to describe predictors of immune recovery and initial response to tetanus after DTaP vaccination post-HSCT. We conducted a retrospective chart review of pediatric allo-HSCT patients transplanted between July 1, 2007-June 30, 2012 who survived >1 yr without relapse (N = 27). Response to tetanus one month after the initial dose of DTaP was defined as a ≥4 fold increase in tetanus titers ≥1 month after vaccination. Wilcoxon rank-sum exact test and Kruskall-Wallis tests were used to analyze CD4, CD8, and CD19 counts. Exact conditional logistic regression was utilized to analyze initial tetanus vaccination response. A statistically significant increase in median CD4, CD8, and CD19 counts occurred from six to 12 months post-HSCT (p ≤ 0.0001, 0.005, 0.004). Only 36% of patients had initial tetanus vaccination response at first attempt post-HSCT. None of the variables tested were statistically significant in predicting initial tetanus response to vaccination. There was no association between predictors of immune recovery or transplant variables and initial tetanus response. A uniform vaccination strategy is unlikely to provide protective antibodies for many post-HSCT patients and should be evaluated in larger studies.

Potentiation of vincristine toxicity with concomitant fluconazole prophylaxis in children with acute lymphoblastic leukemia.

Use of azole antifungals as prophylaxis is becoming an increasingly common practice in acute lymphoblastic leukemia (ALL). Limited literature in adults heightened the awareness of possible increased vincristine (VCR) toxicity in patients receiving concomitant azole therapy. This is due to inhibition of cytochrome P450 3A4, which may increase overall exposure to VCR, resulting in dose reductions or omissions. The primary objective of this study was to determine whether the use of fluconazole prophylaxis increases vincristine toxicity in children with ALL. The authors retrospectively evaluated children with ALL between January 2004 and December 2009. Patients were subdivided into 2 groups based on whether or not they received fluconazole prophylaxis during induction therapy. Data were collected for up to 3 months following the completion of induction therapy. Thirty-one patients were included for analysis. There was no significant difference in gender, race, steroid use, gastrointestinal (GI) toxicity, VCR dose modification, and the rate of fungal or bacterial infections between these 2 groups. Only advanced age is an independent predictor of neuropathy. Patients receiving fluconazole were 4.5 times more likely to experience neuropathy than those not receiving azole; however, this was not statistically significant. The authors report an increased incidence of VCR toxicity in patients with ALL receiving concomitant fluconazole prophylaxis. Judicious use of azole antifungals is warranted in children with ALL.

Post-hematopoietic stem cell transplant immunization practices in the Pediatric Blood and Marrow Transplant Consortium.

BACKGROUND: A survey of National Marrow Donor Program transplant centers in 1995 demonstrated a wide range of immunization practices in post-hematopoietic stem cell transplant (HSCT) recipients, which led to the 2000 Centers for Disease Control and Prevention (CDC) recommendations for vaccination after HSCT. We surveyed the principal investigators of the Pediatric Blood and Marrow Transplant Consortium (PBMTC) to identify immunization practice patterns after HSCT and assess compliance with the 2000 CDC guidelines. PROCEDURE: Approval was obtained from the Medical University of South Carolina Institutional Review Board. A 33 question survey using surveymonkey.com was distributed by email to principal investigators in the PBMTC. RESULTS: Forty-one (40%) of the 102 pediatric HSCT centers participating in the PBMTC responded. Thirty of the responding centers completed the entire survey. For individual vaccines, compliance with the CDC guidelines ranged from 22% to 93%. Less than 20% of the centers reported schedules consistent with the 2000 CDC recommendations for both allogeneic and autologous HSCT recipients. CONCLUSION: Despite the 2000 CDC guidelines, wide variation in post-HSCT immunization practices still exists. Updated guidelines have been needed, particularly to address the use of the pneumococcal conjugate vaccine. In conjunction with multiple other groups, the CDC recently released new immunization guidelines in October 2009. Additional data are still needed to adequately address the utility of incorporating immunologic parameters with the timing of vaccination after HSCT.

Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.

This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 microg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high-dose anti-D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti-D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti-D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high-dose anti-D are effective first-line therapies for childhood ITP. However, we observed increased ADRs in the high-dose anti-D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high-dose anti-D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.

First-year residency candidates' experience in various areas of pharmacy practice.

OBJECTIVE: To determine the extent of experience or exposure pharmacy residency candidates had in various areas of hospital pharmacy practice and to identify any candidate-specific variables that correlated with a larger extent of experience. METHODS: Over a 3-year period, a self-assessment survey instrument was administered to 116 postgraduate first-year (PGY1) pharmacy practice residency candidates to evaluate their extent of experience within various areas of hospital pharmacy practice such as patient care activities, drug information, and drug distribution/control. RESULTS: The residency candidates reported the greatest amount of experience in patient counseling, working with pharmacy databases, taking medication histories, pharmacokinetics, and outpatient dispensing procedures. They had less experience with medical emergencies, parenteral nutrition, and intravenous admixture techniques. Overall, there was no correlation between class rank, advanced pharmacy practice experiences, geographic region, or year of interview and the extent of candidates' experience in any specific area of pharmacy. CONCLUSION: PGY1 residency candidates in this sample reported minimal experience in areas necessary for hospital pharmacy practice and this suggests possible deficiencies in the PharmD curriculum. PGY1 residency programs in acute care settings should recognize these educational deficits and assure that residents have exposure to and develop proficiency in critical areas such as medical emergencies, parenteral nutrition, and intravenous admixture techniques.

Hypercalcemia induced by 13-cis-retinoic acid in a patient with neuroblastoma.

Hypercalcemia is a potential dosage-related adverse effect of 13-cis-retinoic acid in patients with neuroblastoma. Severe hypercalcemia requiring dosage reduction has been reported in children receiving 13-cis-retinoic acid 200 mg/m2/day and in those with concurrent renal impairment receiving 160 mg/m2/day. A 12-year-old girl without renal dysfunction, diagnosed with neuroblastoma, developed severe hypercalcemia requiring several hospitalizations while receiving 13-cis-retinoic acid 160 mg/m2/day. Her hypercalcemia resolved with hydration, diuretic therapy, and temporary discontinuation of 13-cis-retinoic acid. Despite a 50% dosage reduction to 80 mg/m2/day, severe hypercalcemia recurred with the next treatment cycle. Further treatment with 13-cis-retinoic acid was made tolerable by shortening the duration of the remaining cycles. Serum calcium levels should be monitored in patients with neuroblastoma who receive 13-cis-retinoic acid.