Pediatric Bone Marrow Transplant Recipients Research Articles

486 - Demographics and Treatment-Related Factors Influence PTSD Symptom Development in Pediatric Bone Marrow Transplant Recipients

486 - Demographics and Treatment-Related Factors Influence PTSD Symptom Development in Pediatric Bone Marrow Transplant Recipients

Utility of Fungal Cell Markers in Pediatric Bone Marrow Transplant Recipients for Screening and Diagnosis of Invasive Fungal Infections

Invasive fungal disease (IFD) is a significant contributor to morbidity and mortality in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Early detection and timely initiation of antifungal therapy is important for improved outcome, but diagnosis remains difficult, especially when relying on conventional microbiology methods such as culture and microscopy. Data on the use of fungal biomarkers for screening and diagnosis of IFD in HSCT pediatric patients are limited, precluding the development of specific guidelines in this population. In this review, we have summarized available literature on kinetics, diagnostic and prognostic performance, and limitations of fungal biomarkers for screening and diagnosis of IFD in pediatric HSCT recipients to help guide their use and interpretation.

Assessment of Iron Overload in the Pediatric Allogeneic HSCT Recipient

Background: Owing to improved strategies in pediatric bone marrow transplantation, a larger number of transplanted children are now becoming long term survivors. These post-transplant patients remain at risk for late complications including iron overload, which has the potential to impair quality of life and adversely affect later outcomes. While literature has previously focused on iron overload in the adult sickle cell patient, there has been minimal research into its effect on the pediatric bone marrow transplant recipient. Thus, no current guidelines exist for screening, management or treatment of iron overload in this patient population. Our study focuses specifically on this population and reports the relationship between number of PRBC transfusions and current diagnostic tools.Objectives: To identify the presence or absence of correlation between the number of red blood cell transfusions and indicators of iron overload via two different modalities: ferritin values and the T2* MRI liver iron concentration (Ferriscan).Methods: A retrospective chart review of the allogeneic pediatric bone marrow transplant patients over the past 5 years at a single center (n = 32). Quantitative data obtained which included number of PRBC transfusions, ferritin, and T2* MRI LIC. Correlation analysis subsequently performed between pre-and post-transplant values.Results: There was significant (p < 0.001) moderate correlation (r = 0.62) between the number of pre-transplant PRBC transfusions and the pre-transplant ferritin value. No significant (p >0.1) correlation between the number of pre-transplant PRBC transfusions and the pre-transplant T2* LIC. Also, no significant (p > 0.1) correlation between pre-transplant ferritin and T2* LIC. The total number of PRBC transfusions up to 100 days post-transplant did have significant (p = 0.008) moderate correlation (r= 0.62) with post-transplant ferritin values. There was significant (p = 0.01) strong correlation (r= 0.87) between the total number of PRBC transfusions up to 100 days post-transplant with post-transplant T2*LIC values. No significant correlation (p > 0.1) between post-transplant ferritin and T2* MRI LIC values.Conclusions: In terms of modalities utilized for evaluation of iron overload in the pediatric allogeneic BMT population, no significant correlation exists between ferritin values and T2* MRI liver iron concentration values. While ferritin is an acceptable screening tool the post-transplant T2*MRI LIC is a more accurate diagnostic indicator of transfusion burden. Future studies will be used to explore associated adverse outcomes of patients diagnosed with iron overload. DisclosuresNo relevant conflicts of interest to declare.

Cytokine Profile of Engraftment Syndrome in Pediatric Hematopoietic Stem Cell Transplant Recipients

The biology of engraftment syndrome is poorly understood, and the degree of overlap with acute graft-versus-host disease (GVHD) is unclear. To understand engraftment syndrome better, plasma cytokine profiles were evaluated in 56 pediatric allogeneic bone marrow transplant recipients before transplant, on the day of stem cell infusion, and weekly until day +100. Patients were divided into 4 groups: those with isolated engraftment syndrome (n = 8), acute GVHD (n = 12), both engraftment syndrome and acute GVHD (n = 4), and neither engraftment syndrome nor acute GVHD (n = 32). Engraftment syndrome was observed a median of 13.5 days (range, 10 to 28) after transplant, whereas acute GVHD was diagnosed a median of 55 days (range, 19 to 95) after transplant. Four patients developed both engraftment syndrome at a median of 10.5 days (range, 10 to 11) and acute GVHD at a median of 35 days (range, 23 to 56) after stem cell infusion. Median plasma levels of IL-1β, IL-6, IL-12, IL-4, and IL-13 were significantly elevated in patients with isolated engraftment syndrome when compared with isolated acute GVHD. A rise of proinflammatory cytokines (IL-1β, IL-6, and IL-12) was followed by surge in anti-inflammatory cytokines (IL-4 and IL-13) in patients with isolated engraftment syndrome. The observation of elevated IL-1β suggests that engraftment syndrome could be an inflammasome mediated phenomenon.

No evidence of transfusion transmission of Adenovirus and Epstein-Barr virus infections in paediatric recipients post-bone marrow transplant.

Adenovirus and Epstein-Barr virus can cause significant morbidity and mortality in paediatric patients post-bone marrow transplant. The source of infection is thought to be either reactivation of latent viruses or primary infection. We have investigated whether transfusion of blood components from viraemic donors could provide a route of primary infection in these patients and sought the prevalence of viraemia in the blood donor population from England. In 32 linked donor/recipient samples and 300 unselected blood donors, we found no evidence to suggest that these infections in paediatric bone marrow transplant recipients had been acquired from transfused blood components.

Immunohistochemical detection of KI polyomavirus in lung and spleen

Little is known about the tissue tropism of KI polyomavirus (KIPyV), and there are no studies to date describing any specific cell types it infects. The limited knowledge of KIPyV tropism has hindered study of this virus and understanding of its potential pathogenesis in humans. We describe tissues from two immunocompromised patients that stained positive for KIPyV antigen using a newly developed immunohistochemical assay targeting the KIPyV VP1 (KVP1) capsid protein. In the first patient, a pediatric bone marrow transplant recipient, KVP1 was detected in lung tissue. Double immunohistochemical staining demonstrated that approximately 50% of the KVP1-positive cells were CD68-positive cells of the macrophage/monocyte lineage. In the second case, an HIV-positive patient, KVP1 was detected in spleen and lung tissues. These results provide the first identification of a specific cell type in which KVP1 can be detected and expand our understanding of basic properties and in vivo tropism of KIPyV.

Functional Hyposplenism in Pediatric Chronic Graft-Versus-Host Disease

AbstractAbstract 4493 Introduction:Functional hyposplenism is a well-recognized complication of chronic graft versus host disease (cGVHD). Whether the hyposplenism in cGVHD is transient and if there is any association between the severity of cGVHD and degree of hyposplenism are not well understood. The pitted red cell count has been shown to be a simple and reliable biomarker of splenic function that correlates well to other tests such as quantitative Howell-Jolly bodies and 99mTc sulfur-colloid liver-spleen scans. It measures the ability of the splenic red pulp to pinch off intracellular vesicles, or pits, from red blood cells as they pass through narrow adjustable slits in an endothelial lining. Methods:We hypothesized that functional hyposplenism correlates with the severity of cGVHD in pediatric BMT patients. We performed a single-center, retrospective review of pediatric allogeneic bone marrow transplant (BMT) patients who had more then one pit count performed post-BMT and clinical diagnosis of cGVHD based on NIH consensus criteria. Results:We identified 9 pediatric BMT recipients (3 males, 6 females; average age at BMT = 9.6 years) that met our criteria. Indications for BMT were AML (2), ALL (1), biphenotypic acute leukemia (1), CML (2) and thalassemia (3). All 9 had functional hyposplenism with active cGVHD as determined by a pit count > 2%. We identified two distinct groups. In 7 of the 9 BMT recipients, there was a return to normal splenic function that lagged between 12 and 18 months after clinical improvement/resolution of cGVHD symptoms and successful weaning of immunosuppressive therapy. In the other 2 patients there was no correlation between abnormal pit count and cGVHD symptoms. Conclusions:Our single-centre retrospective cohort study provides evidence that the functional hyposplenism associated with cGVHD is not permanent but improvement in cGVHD symptoms and successful weaning of immunosuppressive therapy should not be used as indicators of return to normal splenic function and reasons to stop Penicillin prophylaxis. We propose that all patients post-BMT should have serial pit counts performed, as resolution of cGVHD clinical symptoms does not ensure normal splenic function. Disclosures:No relevant conflicts of interest to declare.

BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: Treatment response and evidence for nosocomial transmission

BackgroundBK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads. ObjectivesCharacterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment. Study designBy prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments). ResultsDecreasing BKV viremia of>2log10copies/mL and clinical resolution was seen in 4 patients over 5–12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patients ConclusionsThe data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir.

Safety of Liposomal Cytarabine Prophylaxis in Pediatric Bone Marrow Transplant (BMT) Recipients with Acute Leukemia (AL) and Non Hodgkin Lymphoma (NHL) at High Risk of Cns Relapse

Abstract Abstract 4249 BACKGROUND: Liposomal Cytarabine is a derivative of cytarabine designed for intrathecal or intraomaya treatment of leukemia/lymphomatous meningitis (LLM). This formulation allows for sustained release with prolonged therapeutic concentration and drug exposure of 8 to 14 days in children and adults, respectively. Adult trials have shown liposomal cytarabine 50mg to be both safe and effective in the treatment of LLM (Glantz et al, JCO 1999). Bomgaars et al. investigated the use of liposomal cytarabine in children in a phase I dose escalation trial and demonstrated the maximal tolerated dose to be 35mg and that it was safe, well tolerated and effective (Bomgaars et al., JCO 2004). Comparisons of liposomal cytarabine use with conventional methotrexate prophylaxis suggest an improved quality adjusted survival benefit for patients where any possible additional toxicities are out measured by prolonged overall survival (Cole et al, Cancer 2003). However, there remains a paucity of data on the use of liposomal cytarabine prophylaxis to prevent LLM in pediatric patients, particularly in pediatric allogeneic stem cell (AlloSCT) recipients. Review of the literature reveals conflicting data concerning the efficacy of intrathecal chemoprophylaxis in children with leukemia/lymphoma after hematopoietic stem cell transplant. Recent multicenter trials suggest no statistically significant difference in the incidence of isolated or mixed CNS relapses between children receiving standard post-SCT intrathecal prophylaxis versus those that received no prophylaxis (Rubin et al., BMT 2011). This highlights the need to explore alternative chemoprophylaxis strategies in these high risk patients so that significant progress can be achieved. OBJECTIVE: We report on the safety and tolerability of liposomal cytarabine prior to and following allogeneic or autologous stem cell transplant in pediatric BMT recipients with AL and NHL. METHODS: Pediatric stem cell recipients with a history of AL or NHL and high risk of CNS disease received liposomal cytarabine 35mg ( 21yr) via lumbar puncture or omaya resevoir pre conditioning and approximately every 3months for 1–2yrs post stem cell transplant. No other intrathecal prophylaxis was administered. Patients received dexamethasone (0.15mg/kg/dose BID) concomitantly × 5days. Eight patients received a 9/10 or 10/10 matched unrelated donor transplant, 1 patient received an 8/10 matched unrelated donor. There were 9 matched related donor transplants and 3 autologous transplants. Twelve patients received a TBI (1200 cGy) based myeloablative conditioning regimen. Seven patients received an additional CNS boost of up to 1200 cGy during conditioning. All allogeneic SCT recipients received GVHD prophylaxis as previously described (Oswunko/Cairo, BBMT 2004; Bhatia et al, BBMT 2009) with tacrolimus and MMF. RESULTS: To date there have been 21 patients: (12 ALL, 2 AML, 3 Burkitt, 3 DLBCL and 1 T-LL). At the time of transplant, 7 patients were CR1/PR1, 10 patients CR2 and 4 patients CR3. Among all patients, they have received a total of 46 doses (median=1, range 1–12). Median age: 12yr (range 6–22). Mean follow up: 517 days (median= 294days). Eight of 21 patients had a history of CNS AL/NHL involvement prior to AlloSCT. No patients had evidence of LLM at the time of AlloSCT. Two patients experienced Grade II-III headache. Grade II-III vomiting was also noted in 2 additional patients. Head CT scans that were done at the time of symptom occurrence were negative for any evidence of hydrocephalus, hemorrhage, infarct or inflammation in all patients. Patients were treated with supportive therapy and had complete resolution of symptoms. Seven patients developed relapsed systemic disease, but none relapsed in the CNS. An additional 3 patients are deceased secondary to multi organ failure and 2 patients from overwhelming infection. However, none of the above patients had CNS AL/NHL at time of death. CONCLUSION: These preliminary results suggest that prophylactic liposomal cytarabine is tolerable and effective in pediatric AlloSCT and AutoSCT recipients at risk for CNS relapse. Larger studies are needed in the future to compare this to other CNS prophylaxis regimens post auto or AlloSCT. In addition, trials are in development to investigate the combination of intraomaya Rituximab followed by liposomal Cytarabine in children with recurrent/refractory CNS CD20+ AL/NHL. Disclosures: No relevant conflicts of interest to declare.

High Dose Methylprednisolone for Veno-Occlusive Disease of the Liver in Pediatric Bone Marrow Transplant Recipients

High Dose Methylprednisolone for Veno-Occlusive Disease of the Liver in Pediatric Bone Marrow Transplant Recipients

Safety of Liposomal Cytarabine Prophylaxis in Pediatric Bone Marrow Transplant (BMT) Recipients with Acute Leukemia (AL) and Non Hodgkin Lymphoma (NHL) At High Risk of CNS Relapse

Abstract 4249 BACKGROUND:Liposomal Cytarabine is a derivative of cytarabine designed for intrathecal or intraomaya treatment of leukemia/lymphomatous meningitis (LLM). This formulation allows for sustained release with prolonged therapeutic concentration and drug exposure of 8 to 14 days in children and adults, respectively. Adult trials have shown liposomal cytarabine 50mg to be both safe and effective in the treatment of LLM (Glantz et al, JCO 1999). Bomgaars et al. investigated the use of liposomal cytarabine in children in a phase I dose escalation trial and demonstrated the maximal tolerated dose to be 35mg and that it was safe, well tolerated and effective (Bomgaars et al., JCO 2004). Comparisons of liposomal cytarabine use with conventional methotrexate prophylaxis suggest an improved quality adjusted survival benefit for patients where any possible additional toxicities are out measured by prolonged overall survival (Cole et al, Cancer 2003). However, there remains a paucity of data on the use of liposomal cytarabine prophylaxis to prevent LLM in pediatric patients, particularly in pediatric allogeneic stem cell (AlloSCT) recipients. Review of the literature reveals conflicting data concerning the efficacy of intrathecal chemoprophylaxis in children with leukemia/lymphoma after hematopoietic stem cell transplant. Recent multicenter trials suggest no statistically significant difference in the incidence of isolated or mixed CNS relapses between children receiving standard post-SCT intrathecal prophylaxis versus those that received no prophylaxis (Rubin et al., BMT 2011). This highlights the need to explore alternative chemoprophylaxis strategies in these high risk patients so that significant progress can be achieved. OBJECTIVE:We report on the safety and tolerability of liposomal cytarabine prior to and following allogeneic or autologous stem cell transplant in pediatric BMT recipients with AL and NHL. METHODS:Pediatric stem cell recipients with a history of AL or NHL and high risk of CNS disease received liposomal cytarabine 35mg (<21yr) or 50mg (>21yr) via lumbar puncture or omaya resevoir pre conditioning and approximately every 3months for 1–2yrs post stem cell transplant. No other intrathecal prophylaxis was administered. Patients received dexamethasone (0.15mg/kg/dose BID) concomitantly × 5days. Eight patients received a 9/10 or 10/10 matched unrelated donor transplant, 1 patient received an 8/10 matched unrelated donor. There were 9 matched related donor transplants and 3 autologous transplants. Twelve patients received a TBI (1200 cGy) based myeloablative conditioning regimen. Seven patients received an additional CNS boost of up to 1200 cGy during conditioning. All allogeneic SCT recipients received GVHD prophylaxis as previously described (Oswunko/Cairo, BBMT 2004; Bhatia et al, BBMT 2009) with tacrolimus and MMF. RESULTS:To date there have been 21 patients: (12 ALL, 2 AML, 3 Burkitt, 3 DLBCL and 1 T-LL). At the time of transplant, 7 patients were CR1/PR1, 10 patients CR2 and 4 patients CR3. Among all patients, they have received a total of 46 doses (median=1, range 1–12). Median age: 12yr (range 6–22). Mean follow up: 517 days (median= 294days). Eight of 21 patients had a history of CNS AL/NHL involvement prior to AlloSCT. No patients had evidence of LLM at the time of AlloSCT. Two patients experienced Grade II-III headache. Grade II-III vomiting was also noted in 2 additional patients. Head CT scans that were done at the time of symptom occurrence were negative for any evidence of hydrocephalus, hemorrhage, infarct or inflammation in all patients. Patients were treated with supportive therapy and had complete resolution of symptoms. Seven patients developed relapsed systemic disease, but none relapsed in the CNS. An additional 3 patients are deceased secondary to multi organ failure and 2 patients from overwhelming infection. However, none of the above patients had CNS AL/NHL at time of death. CONCLUSION:These preliminary results suggest that prophylactic liposomal cytarabine is tolerable and effective in pediatric AlloSCT and AutoSCT recipients at risk for CNS relapse. Larger studies are needed in the future to compare this to other CNS prophylaxis regimens post auto or AlloSCT. In addition, trials are in development to investigate the combination of intraomaya Rituximab followed by liposomal Cytarabine in children with recurrent/refractory CNS CD20+ AL/NHL. Disclosures:No relevant conflicts of interest to declare.

The role of cytomegalovirus infection and disease in pediatric bone marrow transplant recipients in Mexico City in the context of viral drug resistance

We aimed to identify those pediatric patients undergoing ABMT with CMV EOD who developed GCV resistance. Forty-seven patients were analyzed following ABMT. Prospective post-transplant CMV monitoring was performed weekly for the detection of viral leukocyte DNAaemia, viral plasma DNAaemia, and viral DNAuria by PCR. Plasma DNAaemia was confirmed from whole blood by the detection of CMV pp67 late mRNA using NASBA technology. In the cases of persistence of viral DNA in plasma, and positive viral RNA detection in blood, CMV drug resistance screening by comprehensive PCR-based RFLP and sequencing of the viral UL97 gene were performed retrospectively. Thirty of the 47 (63.82%) patients showed active CMV infection with 27/30 (74.4%) patients belonging to the D+R+ group and 25/30 with proven viral replication. In total, 2/30 (6.6%) children developed CMV pneumonia proven by immunohistochemistry. Screening of the viral UL97 gene revealed in one of these two cases (1/30, 3.3%) the simultaneous presence of two point mutations in codon 460 (M460V, M460I) conferring GCV resistance. The CMV seroprevalence (81%) and the incidence of active infection (63.8%) in Mexican children undergoing ABMT are very high.

HPLC‐UV assay for monitoring total and unbound mycophenolic acid concentrations in children

A simple, accurate and sensitive HPLC method was developed for measuring total and unbound mycophenolic acid (MPA) in human plasma. Total MPA was extracted by protein precipitation and ultrafiltration was used to assess unbound MPA concentrations. The supernatant (20 microL) or ultrafiltrate (100 microL) was injected onto a C(18) HPLC column with a mobile phase of 0.05 m sodium phosphate buffer (pH 2.31)-acetonitrile (55:45, v/v for total MPA; 50:50 for unbound MPA) with UV detection at 254 nm. The extraction recovery was over 93% and reproducible. The assay was linear over the concentration range of 0.07-50 mg/L for total MPA and 4-1500 microg/L for unbound MPA. Intra- and inter-day assay reproducibility was less than 10%. Detection limits were 0.04 mg/L and 2 microg/L for total and unbound MPA, respectively. The assay utility was established in samples collected from five paediatric bone marrow transplant recipients who were receiving intravenous doses of mycophenolate mofetil. In these patients MPA concentrations ranged from 0.07 to 7.83 mg/L and unbound drug concentrations ranged from 2.1 to 107.5 microg/L. This method can be effectively applied to MPA pharmacokinetics in paediatric patients.

Bronchoalveolar cytology for diagnosing pulmonary GVHD after bone marrow transplant in children

Cytological composition of bronchoalveolar lavage (BAL) fluid in pediatric bone marrow transplant (BMT) recipients with pulmonary complications has not been comprehensively described and BAL specific markers of pulmonary GVHD are lacking. The aim of this retrospective study was to assess the role of BAL in the diagnosis of pulmonary GVHD by comparing BAL cytological findings between pediatric allogenic BMT patients with pulmonary complications and oncology children receiving chemotherapy alone. Retrospective analysis of BAL specimens for cytology, total and differential cell counts and presence of infections. Seventeen BMT and 13 chemotherapy BAL were analyzed. BAL total cell count was increased but similar between groups (96.9 x 10(4) vs. 98.2 x 10(4), P = NS). BAL cellular composition differed considerably between groups with a significantly higher number of lymphocytes (18% vs. 6.25%, P = 0.03) and a significantly lower number of neutrophils (25.9% vs. 58%, P = 0.02) in BMT BAL specimens. Atypical epithelial cells were significantly more frequent (75% vs. 30.8%, P = 0.027), and significantly more severe (P = 0.01) in BMT patients. The presence and severity of atypia was not associated with infection or pneumotoxic drug exposure (P = NS). BAL cytology differs significantly between BMT and chemotherapy patients. The presence BAL lymphocytosis and severe epithelial cell atypia concomitantly to respiratory symptoms and GVHD in other organs may suggest the diagnosis of pulmonary GHVD. Prospective studies assessing the reliability of this finding combined with markers such as epithelial cell apoptosis and increased cytokines are needed.

199: Risk Factor Analysis and EBV Load Surveillance in Pediatric Bone Marrow Transplant Recipients

199: Risk Factor Analysis and EBV Load Surveillance in Pediatric Bone Marrow Transplant Recipients

Supporting Siblings Through the Pediatric Bone Marrow Transplant Trajectory

When a child undergoes bone marrow transplant (BMT), the entire family is affected by the demands of the transitions encountered throughout the BMT experience. Although there is a growing body of knowledge on how healthy siblings adjust to the BMT experience, there is still much to be learned. Part of a larger study aimed at detailing healthy siblings' lived experiences of BMT, this article presents findings specific to one of the study's objectives that focused on understanding siblings' perspectives of how nurses and other health professionals can best support siblings throughout the BMT trajectory. A qualitative research study guided by the philosophy of hermeneutic phenomenology was conducted. Eight siblings of pediatric BMT recipients were recruited. Semistructured, open-ended interviews, demographic data, and field notes were the primary sources of data. Interview transcripts were analyzed and interpreted using van Manen's approach. Seven themes emerged: (1) include me in the definition of "family," (2) be caring, (3) share information with me, (4) give me choices, (5) help me share my feelings, (6) provide opportunities for me to meet my peers, and (7) create a healthy hospital environment. Findings showed that siblings have definite thoughts about how nurses and other health professionals should support them, but their support needs are not being met.

3469: Focused abdominal sonography for gastrointestinal complications in pediatric bone marrow transplant recipients

Bone marrow transplantation(BMT) is widely used in the treatment of hematologic disorders and some solid tumors in children. A wide variety of complications may occur in BMT recipients and are a major cause of morbidity and death. The gastrointestinal tract is a frequently affected organ after BMT. Gastrointestinal complications include neutropenic colitis, CMV enterocolitis, pseudomembranous colitis, GVHD, pneumatosis intestinalis and post-transplantation lymphoproliferative disease (PTLD). In pediatric age, ultrasonography is used for modality of choice and essential tool for diagnosing these complications in critically ill recipients. We present US features of these many gastrointestinal complications with correlative other abdominal imaging, including plain radiography, contrast studies and enhanced CT scans.

54 A prospective study of Parvovirus B19 infections in pediatric solid-organ and bone marrow transplant recipients and pediatric solid tumor patients: Preliminary results

54 A prospective study of Parvovirus B19 infections in pediatric solid-organ and bone marrow transplant recipients and pediatric solid tumor patients: Preliminary results

Prospects for adenovirus antivirals

Adenoviruses cause a number of self-limiting but often highly infectious diseases that affect multiple organs, most commonly those associated with respiratory, genitourinary and gastrointestinal tracts and the ocular surface. Many factors have driven a search for effective topical and systemic antivirals to adenoviruses. These include patient morbidity, economic losses and chronic visual disturbances associated with epidemic keratoconjunctivitis; and the startling recent trend of high morbidity and rising mortality associated with systemic adenoviral infections in the immunosuppressed, particularly paediatric bone marrow transplant recipients. The development of effective antivirals has proven to be a complex task, owing to the fact that multiple and often genetically divergent adenovirus serotypes can cause similar diseases. Currently, there remains no licensed systemic or topical treatment in the USA or Europe. However, many compounds have been explored for activity against adenoviruses, and some have been evaluated clinically in either a topical setting for ocular disease or in the setting of systemic treatment in the face of life-threatening adenovirus infections. This article outlines such compounds, discusses the potential for their clinical development, and highlights some problems that may be faced in evaluating their efficacy clinically.

Drug Therapy in the Heart Transplant Recipient

Received March 16, 2004; revision received July 23, 2004; accepted September 30, 2004. With improving survival, the heart transplant recipient faces an increasing number of medical problems caused by both aging and the cumulative complications of immunosuppressive drugs.1 The availability of new drugs to treat infection, obesity, hypertension, hyperlipidemia, renal insufficiency, diabetes, osteoporosis, gout, and malignancies has resulted in the heart transplant recipient and their physicians facing an almost overwhelming number of important drug–drug interactions. In parts 1 through 3 of this series, we reviewed commonly used immunosuppressive drugs and their pharmacology, as well as the common medical problems faced by the heart transplant recipient. In this article, we provide an overview of the mechanisms of common and important potential drug–drug interactions and guidelines for avoiding these interactions. The risk for drug–drug interactions is increased by advanced age, polypharmacy, medications with a narrow therapeutic index, or medications requiring intensive monitoring. All of these factors except advanced age are present in the heart transplant recipient. A 10-fold interpatient variability may exist in the magnitude of a drug interaction resulting from patient-related and drug-related factors.2 Patient-related factors predisposing to drug interactions include concomitant diseases, genetics, diet, and environmental exposures. For example, commonly used immunosuppressants, antifungal agents, and lipid-lowering medications are metabolized through the cytochrome P450 (CYP450) enzyme system and effluxed from cells by the multiple drug resistance transporter protein p-glycoprotein (P-gp). Both systems are found in the liver and gastrointestinal tract and exhibit genetic polymorphism.2 The CYP450 enzymes belong to a superfamily of oxygenases; the primary purpose of these oxygenases is to add a functional group to a drug to increase its polarity and to promote its excretion from the body. If enzymes possess >40% homology, they are grouped together into families designated by an Arabic numeral (eg, the …