Jennifer Domm

Use of Intravenous Zanamivir after Development of Oseltamivir Resistance in a Critically Ill Immunosuppressed Child Infected with 2009 Pandemic Influenza A (H1N1) Virus

Immunosuppressed patients receiving oseltamivir for 2009 novel H1N1 influenza A infection may develop drug resistance, leading to treatment failure. Intravenous zanamivir was administered on a compassionate-use basis to a profoundly immunosuppressed pediatric patient with severe oseltamivir-resistant novel H1N1 pneumonia. The regimen was well tolerated and was associated with a decrease in viral burden.

Unrelated umbilical cord blood transplantation in children with immune deficiency: results of a multicenter study

In the absence of a related donor, unrelated cord blood transplant (CBT) may be a potential option for patients with a primary immune deficiency (PID). Most published experience consists of single-center data using multiple preparative regimens and GVHD prophylaxis. We report the results of a multicenter prospective trial of unrelated CBT for PID. A total of 24 children with PID, with a median age of 1 year (range: 0.23–7.81 years) and a median weight of 10.5 kg (range: 4–24.4 kg) received unrelated CBT between 1999 and 2003. All patients received a fully ablative conditioning regimen with identical GVHD prophylaxis and supportive care. Most patients (79%) received a 1 or 2 HLA Ag-mismatched cord unit with a median nucleated cell infused of 9.3 × 107/kg (range: 1.0–31.2) and a median CD34 of 2.7 × 105/kg 2.9 (range: 0.6–84.5). The cumulative incidence of neutrophil engraftment by day 42 was 58% (95% CI: 38–79%) at a median of 19 days. Cumulative incidence estimates of grade III–IV acute GVHD at day 100 and chronic GVHD at 1 year were 29% (95% CI: 10–48%) and 24% (95% CI: 3–44%), respectively. The probability of survival at 180 days and 1 year was 66.7% (95% CI: 44.3–81.7%) and 62.5% (95% CI: 40.3–78.4%), respectively. Unrelated CBT should be considered in children with PID.

Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants.

Purpose:The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.Methods:Investigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan–Meier survival analyses were conducted for the overall population and for treated and untreated patients.Results:Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).Conclusions:These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.Genet Med 18 5, 452–458.

Impact of Conditioning Regimen in Allogeneic Hematopoetic Stem Cell Transplantation for Children with Acute Myelogenous Leukemia beyond First Complete Remission: A Pediatric Blood and Marrow Transplant Consortium (PBMTC) Study

Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial. Because the long-term morbidity of busulfan (Bu)-based regimens appears to be lower, determining efficacy is critical. We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen. There were no differences between the 2 groups with respect to age, sex, duration of CR1, time from most recent remission to transplantation, or donor source. The probability of relapse at 2 years also did not differ between the 2 groups (26% and 27%, respectively; P=.93). No significant difference in event-free survival (EFS) (P=.29) or overall survival (OS) (P=.11) was noted between the 2 groups. These findings were supported by a multivariate analysis in which TBI was not associated with improved EFS (hazard ratio [HR]=1.17; 95% confidence interval [CI]=0.66-2.10; P=.58) or OS (HR=1.42; 95% CI=0.76-2.64; P=.27). Shorter CR1 and receiving an HLA-mismatched transplant adversely affected EFS and OS in this cohort. Our study provides no evidence of an advantage to using TBI in children with AML beyond CR1. A prospective, randomized study is needed to confirm these results.

Preengraftment Syndrome after Unrelated Cord Blood Transplant Is a Strong Predictor of Acute and Chronic Graft-versus-Host Disease

Preengraftment syndrome (PES) is a known complication following unrelated cord blood transplant (CBT) that has not been well characterized. We sought to determine the incidence and clinical outcome of PES among 326 patients <18 years of age who were prospectively enrolled on a multicenter CBT trial. All patients received a myeloablative (MA) transplant and a single cord blood unit (CBU). PES developed in 20% of the patients at a median of 10 days (range: 5-24). Patients receiving a CBU with a total nucleated cell (TNC) count of >5 x 10(7)/kg had significantly higher risk of developing PES (P = .02). There were significantly higher rates of grade II-V (P < .001), grade III-IV (P < .001) acute and chronic (P = .002) graft-versus-host disease (aGVHD, cGVHD) in those who developed PES. In a multivariate analysis, PES did not significantly affect overall survival (OS) (P = .38). We conclude that PES is common following CB transplant (CBT) and additional more intensive immune suppression might be considered to decrease the risk of developing aGVHD and cGVHD.

Acyclovir-resistant herpes simplex virus pneumonia post-unrelated stem cell transplantation: A word of caution

Abstract: HSV causes serious complications in immunocompromised patients, especially SCT recipients. Although ACV is an effective antiviral prophylaxis, the emergence of ACV resistance is a growing problem. The authors describe two cases of fatal ACV‐resistant HSV in two pediatric patients following unrelated donor SCT. Despite the in vitro sensitivity of the HSV isolates to foscarnet, both patients failed to respond to foscarnet therapy. Other antiviral therapies should be considered in those patients who fail to show rapid clinical improvement.

Targeted Busulfan therapy with a steady-state concentration of 600-700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant

Busulfan (BU) has a narrow therapeutic window and the average concentration of BU at steady state (Css) is critical for successful engraftment in children receiving BU as part of the preparative regimen for allogeneic transplants. Sixteen patients with sickle cell disease (SCD) underwent allogeneic bone marrow transplant (BMT) from HLA-identical siblings. The preparative regimen consisted of intravenous BU 0.8–1 mg/kg/dose for 16 doses, cytoxan (CY) of 50 mg/kg daily for four doses and equine anti-thymocyte globulin (ATG) 30 mg/kg daily for three doses. BU levels were adjusted to provide a total exposure Css of 600–700 ng/mL. The median age at the time of transplant was 6.2 years (range 1.2–19.3). Fourteen (87%) patients required adjustment of the BU dose to achieve a median Css of 652 ng/mL (range 607–700). All patients achieved neutrophil and platelet engraftment without significant toxicity. Median donor engraftment at the last follow-up was 100% (range 80–100). None of the patients experienced sickle cell-related complications post transplant. With a median follow-up of 3 years (range 1.3–9), the event-free survival (EFS) and overall survival (OS) are both 100%. We conclude that targeting of BU Css between 600 and 700 ng/mL in this regimen can result in excellent and sustained engraftment in young patients with SCD.

Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies.

Relapse after allogeneic hematopoietic SCT (HSCT) carries a poor prognosis and is a common cause of death. Outcomes of children who relapse post HSCT are not well known. In this retrospective multicenter study we included 532 patients who underwent allogeneic HSCT and examined the outcomes of 160 patients (30%) who relapsed. Treatment options after relapse included (i) palliative therapy with non-curative intent (n=43), (ii) salvage chemotherapy (without a second HSCT, n=55) or (iii) salvage chemotherapy followed by a second HSCT (n=62). Sixty two patients underwent a second HSCT. The 1-year disease-free survival (DFS) for those given palliative therapy, chemotherapy alone and who underwent a second transplant was <1%, 9% and 50% (P=<0.0001), respectively. The DFS at 1 and 2 year was 50% and 35%, respectively, among the patients who received a second transplant versus 9% and 2% in those who did not (P=<0.0001). In multivariable analysis longer time to relapse (P=0.04) and undergoing a second HSCT (P<0.001) were associated with improved outcome. Withdrawal of immunosuppressive therapy, followed by curative intent chemotherapy should be offered to all patients who relapse after an allogeneic HSCT. A second HSCT should be considered, especially in patients who respond to salvage chemotherapy.

Attitudes of First-year Medical Students Toward the Confidentiality of Computerized Patient Records

OBJECTIVES To investigate the attitudes of students entering medical school toward the confidentiality of computerized medical records. DESIGN First-year medical students at the Vanderbilt University School of Medicine responded to a series of questions about a hypothetic breach of patients privacy through a computerized patient record system. MEASUREMENTS The individual authors independently grouped the blinded responses according to whether they were consistent with then-current institutional policy. These preliminary groupings were discussed, and final categorizations were made by consensus. RESULTS While most students had a sense of what was right and wrong in absolute terms, half the class suggested at least one course of action that was deemed to be inconsistent with institutional policies. CONCLUSIONS The authors believe that medical schools should directly address ethical and legal issues related to the use of computers in clinical practice as an integral part of medical school curricula. Several teaching approaches can facilitate a greater awareness of the issues surrounding technology and medicine.

Unrelated stem cell transplant for infantile idiopathic myelofibrosis

Idiopathic myelofibrosis (IMF) is a rare disease in children that can present during infancy and have a protracted course. The only known curative approach for this disease in adult patients is allogeneic stem cell transplant. We present two cases of IMF during infancy that did not resolve with supportive care measures. Both patients underwent unrelated stem cell transplant with complete resolution of their hematologic manifestations and resolution of the bone marrow fibrosis. Pediatr Blood Cancer 2009;52:893–895.