Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: An IRB-approved, retrospective cohort study of children diagnosed with newly-diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17% respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR] 1.7; p=0.0072), clinically-documented infection (aHR 1.73; p=0.025), and likely bacterial infection (aHR 1.86; p=0.008). Conversely, vitamin A deficiency was associated solely with a reduced risk of sepsis (aHR 0.19; p=0.027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

Healthcare-Associated Infections Caused by Mycolicibacterium neoaurum.

Mycolicibacterium neoaurum is a rapidly growing mycobacterium and an emerging cause of human infections. M. neoaurum infections are uncommon but likely underreported, and our understanding of the disease spectrum and optimum management is incomplete. We summarize demographic and clinical characteristics of a case of catheter-related M. neoaurum bacteremia in a child with leukemia and those of 36 previously reported episodes of M. neoaurum infection. Most infections occurred in young to middle-aged adults with serious underlying medical conditions and commonly involved medical devices. Overall, infections were not associated with severe illness or death. In contrast to other mycobacteria species, M. neoaurum was generally susceptible to multiple antimicrobial drugs and responded promptly to treatment, and infections were associated with good outcomes after relatively short therapy duration and device removal. Delays in identification and susceptibility testing were common. We recommend using combination antimicrobial drug therapy and removal of infected devices to eradicate infection.

Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1.

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia. METHODS: We performed a dual-center, phase 1-2 safety and efficacy study of a lentiviral vector to transfer IL2RG complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1. RESULTS: Eight infants with SCID-X1 were followed for a median of 16.4 months. Bone marrow harvest, busulfan conditioning, and cell infusion had no unexpected side effects. In seven infants, the numbers of CD3+, CD4+, and naive CD4+ T cells and NK cells normalized by 3 to 4 months after infusion and were accompanied by vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. The eighth infant had an insufficient T-cell count initially, but T cells developed in this infant after a boost of gene-corrected cells without busulfan conditioning. Previous infections cleared in all infants, and all continued to grow normally. IgM levels normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementation; three of these four infants had a response to vaccines. Vector insertion-site analysis was performed in seven infants and showed polyclonal patterns without clonal dominance in all seven. CONCLUSIONS: Lentiviral vector gene therapy combined with low-exposure, targeted busulfan conditioning in infants with newly diagnosed SCID-X1 had low-grade acute toxic effects and resulted in multilineage engraftment of transduced cells, reconstitution of functional T cells and B cells, and normalization of NK-cell counts during a median follow-up of 16 months. (Funded by the American Lebanese Syrian Associated Charities and others; LVXSCID-ND ClinicalTrials.gov number, NCT01512888.).

Managing local-regional failure in children with high-risk neuroblastoma: A single institution experience.

BACKGROUND: Intensification of systemic therapy for high-risk neuroblastoma (HRNB) has resulted in improved local control and overall survival (OS) leaving potential for de-escalation of primary site radiotherapy. The utility of primary site de-escalation should be evaluated in the context of potential for successful local-regional salvage. We evaluated salvage strategies and outcomes in patients with HRNB with local-regional recurrence as a component of first failure. METHODS: Twenty of 89 patients with HRNB experienced local-regional recurrence as a component of first relapse after chemotherapy, radiotherapy, surgery, and stem cell transplant from 1997 to 2013. We reviewed salvage therapy strategies and disease control, and report on the impact of local therapy as salvage for local-regional relapse. RESULTS: Six of 20 patients with local-regional failure (LRF) were alive after a median follow-up of 13 years (range, 0.9-25.2 years). Median OS was 4.6 years (95% CI, 0.6 to not reached) versus 0.6 years (95% CI, 0.05-2.6) after LRF with and without distant failure, respectively (P = 0.03). OS in patients receiving salvage radiotherapy was comparable to those receiving initial adjuvant but no salvage radiotherapy. Time to first failure and death was significantly impacted by the intensity of frontline systemic therapy (P = 0.03). Salvage radiotherapy reduced the hazard for subsequent LRF (hazard ratio 0.3, 95% CI 0.1-0.9, P = 0.04) but not OS (P = 0.07). CONCLUSIONS: Our study highlights the potential of local control strategies at first failure in patients with LRF when primary site radiotherapy was initially omitted, and delineates potential selection factors which may further improve the therapeutic ratio.

Selective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion.

BACKGROUND: T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. METHODS: Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. RESULTS: Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/µL vs 10/µL; P < .001), and higher T-cell diversity by Vbeta spectratyping at Day +100 (P < .001). Importantly, these recipients experienced a significant reduction in both the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus, Epstein-Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3-depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02). CONCLUSION: CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia.

Haploidentical Donor Transplantation Using a Novel Clofarabine-containing Conditioning Regimen for Very High-risk Hematologic Malignant Neoplasms.

Recurrent/refractory hematologic malignancies have a poor prognosis, and there is a need for novel treatment regimens that can be tolerated by this heavily pretreated patient group. Clofarabine has antileukemic activity with an acceptable toxicity profile. In a phase I clinical trial (NCT00824135), we substituted clofarabine for fludarabine in a well-established reduced-intensity conditioning regimen for a T cell-depleted, mismatched-related (haploidentical) donor transplant backbone and explored the maximum tolerated dose of clofarabine in this combination in 15 patients undergoing hematopoietic cell transplantation for recurrent/refractory or secondary leukemia. Clofarabine was well tolerated at a dose of 50 mg/m/d for 5 days in this regimen, with minimal treatment-related mortality in a heavily pretreated group of high-risk patients. All patients exhibited quick hematopoietic recovery, with median times to neutrophil and platelet engraftment being 11 and 16 days, respectively. Transient elevation of transaminases was the most common toxicity-observed in 13 patients (86.7%), with 6 (40%) grade III or above. Three patients (20%) developed hepatic veno-occlusive disease. Eleven patients (73.3%) died, with the most common cause of death being disease relapse (in 9 patients [60%]), followed by treatment-related mortality (in 2 patients [13.3%]). Four (26.6%) of the patients are long-term survivors.

Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients.

BACKGROUND AND OBJECTIVE: Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents. We evaluated the validity of the bedside Schwartz and Brandt equations in pediatric oncology patients and developed new equations for estimated glomerular filtration rate (eGFR) in these patients. METHODS: A retrospective analysis was conducted comparing eGFR using the bedside Schwartz and Brandt equations to measured GFR (mGFR) from technetium-99m diethylenetriamine pentaacetic acid (99mTc-DTPA) between January 2007 and August 2013. An improved equation to estimate GFR was developed, simplified, and externally validated in a cohort of patients studied from September 2013 to June 2015. Carboplatin doses calculated from 99mTc-DTPA were compared with doses calculated by GFR-estimating equations. RESULTS: Overall, the bedside Schwartz and Brandt equations did not precisely or accurately predict measured GFR (mGFR). Using a data subset, we developed a five-covariate equation, which included height, serum creatinine, age, blood urea nitrogen (BUN), and gender, and a simplified version (two-covariates), which contained height and serum creatinine. These equations were used to estimate GFR in 2036 studies, resulting in precise and accurate predictors of mGFR values. Equations were validated in an external cohort of 570 studies; both new equations were more accurate in calculating carboplatin doses than either the bedside Schwartz or Brandt equation. CONCLUSIONS: Two new equations were developed to estimate GFR in pediatric oncology patients, both of which did a better job at estimating mGFR than published equations.

Phase I study of the safety and pharmacokinetics of plerixafor in children undergoing a second allogeneic hematopoietic stem cell transplantation for relapsed or refractory leukemia.

The safety, pharmacokinetics, and biological effect of plerixafor in children as part of a conditioning regimen for chemo-sensitization in allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is a phase I study of plerixafor designed to evaluate its tolerability at dose of .24 mg/kg given intravenously on day -4 (level 1); day -4 and day -3 (level 2); or day -4, day -3, and day -2 (level 3) in combination with fludarabine, thiotepa, melphalan, and rabbit antithymocytic globulin for a second allogeneic HSCT in children with refractory or relapsed leukemia. Immunophenotype analysis was performed on blood and bone marrow before and after plerixafor administration. Twelve patients were enrolled. Plerixafor at all 3 levels was well tolerated without dose-limiting toxicity. Transient gastrointestinal side effects of National Cancer Institute-grade 1 or 2 in severity were the most common adverse events. The area under the concentration-time curve increased proportionally to the dose level. Plerixafor clearance was higher in males and increased linearly with body weight and glomerular filtration rate. The clearance decreased and the elimination half-life increased significantly from dose level 1 to 3 (P < .001). Biologically, the proportion of CXCR4(+) blasts and lymphocytes both in the bone marrow and peripheral blood increased after plerixafor administration.

Donor-derived anti-HLA antibodies in a haploidentical hematopoietic cell transplant recipient shortly after transplant.

A pediatric patient with acute myeloid leukemia was referred to our institution for investigational therapy after disease relapse following a mismatched unrelated donor hematopoietic cell transplant (HCT). Prior to second HCT, the patient's serum was negative for antibodies to class I and class II HLA. Eight days after receiving a maternal donor haploidentical transplant, the patient became platelet refractory and highly sensitized to multiple class I HLA. Serum from the patient's mother was positive for the strongest antibodies present in the patient, suggesting the antibodies were donor-derived. Patient sera showed magnified and expanded sensitization over time in the context of 100% donor chimerism and despite undetectable circulating B cells. Escalating sensitization suggests active transfer of rituximab-resistant antibody-producing passenger lymphocytes from a haploidentical donor to a transplant recipient at the time of progenitor cell infusion. Evaluation of donor sensitization status may be a consideration prior to HLA mismatched HCT.

Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population.

BACKGROUND: Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. METHODS: A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. RESULTS: Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort ( P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m 2 ( P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CONCLUSIONS: CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

PURPOSE: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Posaconazole therapeutic drug monitoring in pediatric patients and young adults with cancer.

BACKGROUND: Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescents, and young adults with cancer. At St. Jude Children's Research Hospital, the recommended posaconazole dose in patients weighing less than 34 kg is 18-24 mg/kg daily, given in 4 divided doses. For patients aged 13 years or older or those weighing 34 kg or more, the recommended dose is 800 mg daily, given orally in 4 divided doses. OBJECTIVE: To determine whether the current posaconazole dosing guidelines achieve target posaconazole plasma concentrations of 0.7 µg/mL or greater. METHODS: This retrospective clinical study examined data from patients who received treatment-dose posaconazole and had at least 1 posaconazole plasma concentration measurement. RESULTS: Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5-23.2). Twenty-one of 33 patients (63.6%) had posaconazole concentrations of 0.7 µg/mL or greater (median 1.4; range 0.7-2.98) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg/day. Patients with concentrations less than 0.7 µg/mL (median 0.4; range 0.025-0.69) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg/day; p = 0.02). Of the 12 patients with concentrations less than 0.7 µg/mL, 7 (58.3%) were aged 13 years or older. CONCLUSIONS: The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients younger than 13 years than in those 13 years or older. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent, and young adult patients with cancer, with routine therapeutic drug monitoring to ensure adequate concentrations.

Cefiderocol Red Wine Urine Syndrome in Pediatric Patients: A Multicenter Case Series.

Cefiderocol is a novel cephalosporin antibiotic with activity against multidrug-resistant gram-negative bacteria and limited pediatric experience. This case series describes 3 immunocompromised children receiving blood transfusion who developed benign red or purple urine with administration of cefiderocol. Interaction with iron from blood products is a possible mechanism. It is important to recognize this phenomenon and distinguish it from hematuria to avoid unnecessary diagnostic testing.

SARS-CoV-2 infection in high-risk children following tixagevimab-cilgavimab (Evusheld) pre-exposure prophylaxis: a single-center observational study.

From 8 December 2021 to 26 January 2023, tixagevimab-cilgavimab (T-C) was authorized for pre-exposure prophylaxis of COVID-19. During this period, we used a multidisciplinary team to communicate, screen, approach, and administer T-C to eligible patients. Twenty-seven patients were eligible. Of these, 24 (88.9%) received at least one dose of T-C and three patients received two doses. Majority of patients were White, non-Hispanic, and women. Only two patients had COVID-19 prior to receiving T-C. Seventeen (70.8%) had received two or more doses of SARS-CoV-2 vaccine. No serious adverse events were noted. Seven patients developed SARS-CoV-2 infection within 180 days of receiving T-C (median 102 days; range 28-135), and only one patient developed severe COVID-19 requiring intensive mechanical ventilation in the intensive care unit.

Human Astrovirus VA1 Encephalitis in Pediatric Patients With Cancer: Report of 2 Cases and Review of the Literature.

Novel human astroviruses (HAstVs) have recently been implicated as rare causes of fatal encephalitis in immunocompromised patients, for which there is no proven treatment. We report 2 cases from our institution in which HAstV-VA1 was detected in the cerebrospinal fluid by metagenomic next-generation sequencing after the initial evaluation revealed no etiology.

Epidemiology, Diagnosis, and Treatment of Clostridioides difficile Infection in Immunocompromised Children.

Clostridioides difficile infection is very common in immunocompromised children. Management is confounded by frequent asymptomatic colonization, multiple alternative etiologies for gastrointestinal symptoms, and high rates of relapse. Important considerations include indications for testing, appropriate choice of diagnostic tests, antibiotic therapy for initial and subsequent episodes, and primary and secondary prevention.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

Pharmacokinetics of alemtuzumab in pediatric patients undergoing ex vivo T-cell-depleted haploidentical hematopoietic cell transplantation.

PURPOSE: Alemtuzumab is a humanized monoclonal antibody against CD52 which is predominantly present on T and B lymphocytes. Alemtuzumab has been used as part of conditioning regimens for prophylaxis against rejection and GVHD. While the mechanism of action is well understood, the pharmacokinetics of this drug in children needed to be studied in more detail especially in the setting of ex vivo T-cell-depleted hematopoietic cell transplantation (HCT). METHODS: Serum alemtuzumab levels were measured at various time points in 13 patients who underwent haploidentical HCT utilizing ex vivo donor T-cell depletion. Alemtuzumab was administered subcutaneously at a cumulative dose of 45 mg/m2 from days - 13 to - 11. A one-compartmental model was used to fit the data using non-linear mixed effects modeling. RESULTS: We determined the median half-life to be 11 days. Alemtuzumab clearance increased with increasing baseline lymphocyte count (p = 0.008). Additionally, clearance increased with weight and age (p ≤ 0.035). AUC of alemtuzumab did not have any significant relationship with type of leukemia, overall survival, engraftment, immune reconstitution, mixed chimerism or GVHD, although the number of subjects in this pilot study was limited. CONCLUSION: Absolute lymphocyte count and body weight affect alemtuzumab clearance. We also demonstrate feasibility of body-surface area-based dosing of alemtuzumab in pediatric HCT patients. Further studies are needed to evaluate the role of monitoring alemtuzumab serum concentrations to balance the prevention of graft rejection and GVHD with the promotion of rapid donor immune reconstitution.

Fluoroquinolone prophylaxis does not increase risk of neuropathy in children with acute lymphoblastic leukemia.

BACKGROUND: Fluoroquinolone antibiotics are frequently utilized in pediatric oncology patients as prophylaxis or step-down therapy following broad spectrum beta-lactam therapy for febrile neutropenia. Concerns regarding neurotoxicity limit the use of these agents. No studies have evaluated the association between fluoroquinolone use and neurotoxicity in pediatric oncology patients receiving other neurotoxic agents such as vincristine. METHODS: An observational cohort study comprising patients aged 0-18 at diagnosis enrolled on a prospective study for treatment of acute lymphoblastic leukemia (ALL) at a pediatric comprehensive cancer center between October 2007 and November 2018. Data for neuropathic pain and sensory or motor neuropathy were collected prospectively, and a Cox proportional hazards regression model was used to evaluate associations between administration of fluoroquinolone antibiotics during induction therapy and subsequent development of vincristine-induced peripheral neurotoxicity (VIPN). RESULTS: A total of 598 participants were enrolled, including 338 (57%) who received fluoroquinolones during induction therapy; of these 470 (79%) were diagnosed with VIPN and 139 (23%) were diagnosed with high-grade (Grade 3+) VIPN. On unadjusted analyses, and analyses adjusted for age and race, there was no evidence of an association between fluoroquinolone exposure and subsequent VIPN (hazard ratio [HR] 0.8, 95% CI 0.5-1.04, P = .08) or high-grade VIPN (HR 1.1, 95% CI 0.4-2.2, P = .87). CONCLUSIONS: The results of this observational study do not show an association between exposure to fluoroquinolone antibiotics during induction therapy for ALL and subsequent development of vincristine-induced peripheral neuropathies, and suggest that a large increase in VIPN is unlikely.

The Aerogen® Solo Is an Alternative to the Small Particle Aerosol Generator (SPAG-2) for Administration of Inhaled Ribavirin.

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.