Dominic Ragucci

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 μg/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.

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 anitfungals is warranted in children with ALL.

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

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.

Folinic acid administration after MTX GVHD prophylaxis in pediatric allo-SCT.

Cyclosporine (CsA) and MTX are commonly used for GVHD prophylaxis in pediatric allo-SCT. Mucositis and hepatic toxicity frequently restrict the delivery of the fourth dose of MTX. Folinic acid (FA) may ameliorate MTX toxicity. We conducted a retrospective chart review of all pediatric patients who received CsA and MTX for GVHD prophylaxis from January 2000 to July 2010. Patients treated before July 2007 (N=29) did not receive FA and those treated from July 2007 onward did receive FA (N=18). Patients who received FA were significantly more likely to receive day +11 MTX (odds ratio (OR) 10.42, 95% confidence interval (CI): 1.21–262.27) but there was no significant difference in Grade III–IV GVHD between the two groups (OR 1.15, 95% CI: 0.08–18.14). FA did not impact relapse-free survival (RFS) (P=0.82). Increased likelihood of receiving day +11 MTX suggests that FA ameliorates MTX toxicity, such as severe mucositis. FA administration for MTX GVHD prophylaxis should be studied in a prospective, randomized fashion.

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.

Severe pruritus and hypothermia as the primary manifestations of Human Herpes Virus-6 encephalitis after pediatric cord blood transplantation

Severe pruritus and hypothermia as the primary manifestations of Human Herpes Virus-6 encephalitis after pediatric cord blood transplantation

Perioral and facial parasthesias associated with intravenous pentamidine use for pneumocystis prophylaxis.

Pentamidine is an antiprotozoal agent commonly used as a second-line agent in the immunocompromised host for Pneumocytis jirovecii chemoprophylaxis [1]. We administer intravenous (i.v.) or aerosolized pentamidine to children unable to tolerate trimethoprim-sulfamethoxazole (TMP-SMZ). Adverse events associated with i.v. pentamidine include hypotension, leukopenia, hypoglycemia, injection-site reactions, elevated liver enzymes, and impaired renal function [2]. Pentamidine-associated neurologic side effects are not commonly observed or reported. We report 4 cases of pentamidineassociated parasthesias in pediatric patients and 1 case in a young adult. All 5 patients received i.v. pentamidine (4 mg/kg) over 1 hour. The patients experienced a range of symptoms, including facial numbness, perioral numbness, and extremity parasthesias. The symptoms occurred at the end of the infusion or immediately post infusion in 4 of the cases. One patient developed perioral numbness and parasthesias in his left hand 15 minutes into the infusion. All episodes resolved within 30 minutes of completion or interruption of the infusion. Each patient was able to complete the infusion. All 5 patients experienced an adverse event with their initial infusions. Of these 5 patients, two continue to receive monthly i.v. pentamidine, with