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.
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.
Background: Intravenous immune globulin (IVIG) and anti-D immune globulin are common first line therapies for pediatric immune thrombocytopenic purpura (ITP). Recently, a prospective randomized study in childhood ITP showed that high dose anti-D immune globulin (75 mcg/kg) was superior to the standard dose (50 mcg/kg) and as effective as IVIG (Tarantino et al Journal of Pediatrics, 2006). Since then, high dose anti-D immune globulin is being increasingly used in children with ITP. However, anti-D immune globulin can be associated with hemolysis and other side effects, especially at higher doses. We review our experience with IVIG and high dose anti-D immune globulin as initial treatment of childhood ITP. Methods: We retrospectively reviewed the electronic medical records of children diagnosed with ITP between January 2003 and May 2008. We collected demographic data, complete blood counts, treatment details, adverse drug reactions (ADRs), and long-term outcome of these patients. Patients received either intravenous immune globulin (1 g/kg) or anti-D immune globulin (75 mcg/kg). All patients included received premedication with acetaminophen and diphenhydramine prior to either treatment. Response was defined by rise in platelet count after one dose or within 7 days of treatment; treatment failure = platelets<30,000/cmm, partial response= 30,000/cmm<platelets<50,000 response=”platelets” full=”” and=”” cmm,=””>50,000/cmm. Results: A total of 53 patients were included for analysis (Table 1). Both groups had similar treatment response and there was no statistical difference in their initial presentation (presence of wet purpura, baseline platelet count, and hemoglobin), length of hospital stay, need for additional treatments, or development of chronic ITP. However, patients who received anti-D immune globulin experienced a higher rate of ADRs, particularly chills and rigors. In addition, 2 patients in the anti-D immune globulin group developed severe anemia requiring medical intervention. One of these 2 patients had hemoglobinuria consistent with intravascular hemolysis. Also, patients with wet purpura had higher rates of treatment failure (32%) compared to those without wet purpura (6%), regardless of the treatment modality. Conclusions: Our study confirms that both IVIG and high dose anti-D immune globulin are effective first line therapies in 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 the safety of high dose anti-D immune globulin and determine the utility of using wet purpura to predict treatment failure. Table 1: Clinical and laboratory characteristics of study patients Parameters Anti-D 75 mcg/kg (n=24) IVIG 1mg/kg (n=29) P value </platelets<50,000> Males, Females 15, 9 13, 16 0.27 Initial platelet count (103/cmm) (25%, 75%) 6 (3, 11) 7 (3.5, 14.5) 0.41 Initial hemoglobin (g/dL) ± SD 12.0 ± 1.3 11.9 ± 1.7 0.78 Treatment Response Failure Partial response Full response Unable to determine 5 (21%) 10 (42%) 9 (38%) 0 (0%) 4 (14%) 9 (31%) 15 (52%) 1 (3%) 0.50 Hemoglobin decrease (g/dL) ± SD 2.23 ± 1.6 1.24 ± 0.8 0.01 Adverse drug reaction, total 14 (58%) 6 (21%) 0.01 Fever 4 (17%) 2 (7%) 0.25 Chills/rigors 9 (38%) 3 (10%) 0.02 Nausea/vomiting 5 (21%) 2 (7%) 0.14 Headache 1 (4%) 3 (10%) 0.38 Severe anemia requiring intervention 2 (8%) 0 (0%) 0.20
SummaryThis report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 lg/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.
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.
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