Days Of Neutropenia Research Articles

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia.

AIMTo evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) population.METHODSAfter IRB approval, all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified. Medical charts were reviewed for demographics, clinical information, development of CDI, complications of CDI, and mortality. Patients with CDI, defined as having a positive stool PCR done for clinical suspicion of CDI, were compared to those without CDI in order to identify predictors of disease. A t-test was used for comparison of continuous variables and chi-square or Fisher’s exact tests were used for categorical variables, as appropriate.RESULTSTwo hundred and twenty-three patients (60.1% male, mean age 61.3 years, 13% MDS, 87% AML) had 594 unique hospitalizations during the study period. Thirty-four patients (15.2%) were diagnosed with CDI. Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001), prior diagnosis of CDI (P < 0.0001), receipt of cytarabine-based chemotherapy (P = 0.015), total days of neutropenia (P = 0.014), and total days of hospitalization (P = 0.005). Gender (P = 0.10), age (P = 0.77), proton-pump inhibitor use (P = 0.73), receipt of antibiotics (P = 0.66), and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSIONCDI is common in the MDS/AML population. Factors significantly associated with CDI in this population include low albumin, prior CDI, use of cytarabine-based chemotherapy, and prolonged neutropenia. In this study, we have identified a subset of patients in which prophylaxis studies could be targeted.

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study

BackgroundBladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia.MethodsThis was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (−)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia.ResultsEpisodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (−), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (−) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3–223.1).ConclusionsCo-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

Febrile Neutropenia Outcome in Hemato-Oncological Patients after the Implementation of an Adapted Therapeutic Protocol at a University Hospital in Uruguay

Background: Febrile neutropenia (FN) is among the leading causes of mortality and morbidity in hemato-oncologic patients undergoing cytotoxic chemotherapy.The management of FN is typically algorithm-driven. The effectiveness in reducing FN related mortality of the antibacterial protocol proposed by the international guidelines is already reported. In this regard, most of the popular guidelines are based on clinical trials conducted in developed countries. Little is known about results in developing countries where patients delay consultation and have socio-cultural vulnerabilities. The aim of our study was to assess the results of the implementation of a local FN protocol in patients undergoing intensive chemotherapy regimens at Hospital de Clinicas in Uruguay.Methods: We assessed a retrospective study with patients that have undergone intensive chemotherapy in our hemato-oncology service between 2011 and 2014. We included 127 neutropenia episodes (37 patients), with a median age of 37 years (18-79 years). Acute myeloid leukemia 26 (24.4%), acute lymphoblastic leukemia 12 (9.4%), non-Hodgkin lymphoma 74 (58.4%) and Hodgkin Lymphoma 15 (11.8%). Low risk patients were excluded. Additionally, episodes linked with high risk regimens as acute myeloid leukemia induction chemotherapy and alemtuzumab therapy were excluded from the analysis.The initial antibiotic protocol consisted in piperacillin-tazobactam (4.5 gr every 6 hours). For patients with warning signs, more than one week of hospital stay, or having received in the last 30 days ciprofloxacin or 3er generation cephalosporin as prophylaxis meropenem (1gr every 8 hours) was indicated. Prophylactic antiviral (acyclovir) and antifungal (fluconazole) were given in every case. Modification of initial empirical treatment with piperacillin-tazobactam, changing to meropenem, was done if there was: a) deterioration in the clinical state, b) warning signs, hemodynamic instability or other organ dysfunction, c) persistent fever after 4 days of treatment, d) culture with antibiotic-resistant. In patients with hemodynamic instability, skin or soft tissue infection, suspected catheter-related infection or methicillin-resistant Staphylococcus aureus culture positive, vancomycin was added. Empirical antifungal coverage was considered in patients who had persistent fever after 6-7 days of antibiotic treatment without identified fever source.Results: FN incidence was 33.1% (42 episodes). The presence of FN was associated with both the duration and severity of neutropenia. Median days of neutropenia (below 500/μL) in patients with FN was 10.0 ± 7.9 (standard deviation) vs 6.0 ± 3.7 (standard deviation) in patients without FN (p=0,001). Microbiological isolation from any source was achieved in 28.6% of the episodes and bacteremia was the most prevalent (77%). Multiple-antibiotic-resistant (MR) Gram-negative bacillus (GNB) were isolated in 58,3% of all microbiological documented infections, followed by GNB 25%. In 25 episodes the initial treatment was piperacilin/tazobactam (59%), while in 17 episodes Meropenem was. 15 episodes (35.7%) required vacomycin treatment. 32% of the episodes in which the initial treatment was piperacilin/tazobactam, needed to escalate to Meropenem. The mortality rate of febrile neutropenia episodes was 3.9% (40% related to sepsis).Conclusions: In this work we observed high rate of microbiological documentation in FN episodes being bacteriemia the most frequent form and there was a predominance of MR-GNB. The high rate of GNB resistant to piperacilin/tazobactam, front line antibiotics in our protocol, and the early need to escalate to carbapenems raises the question whether it is necessary to change our antibiotic treatment protocol. DisclosuresNo relevant conflicts of interest to declare.

Survival Advantage with Comparable Complete Chimerism Patterns in Reduced Toxicity Treosulfan-Based Vs Reduced Intensity Busulfan-Based Conditinioning Regimen in AML/MDS Patients Undergoing Allogeneic Haematopoietic Cell Transplantation

Introduction: The optimal regimen for patients not fitting criteria for myeloablative conditioning has not yet been established. Treosulfan-based conditioning emerges as a potent antileukemic regimen with high efficacy and low toxicity in acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) patients. The current prospective study was designed to explore both safety and efficacy of FluTreo (fludarabine 150mg/m2, treosulfan 14 gr/m2/d ×3d) in medically infirm patients. Furthermore, we compared the outcome with a control similar population treated with FluBuATG (fludarabine 150mg/m2, busulfex 6.4mg/Kg, thymoglobulin-ATG 5-7.5mg/kg) reduced intensity conditioning.Method: A total of 20 patients, aged 54.5 (34-64) years, suffering from AML (14), MDS (2) and MDS related AML (4), after 3 (1-6) lines of treatment, received a FluTreo conditioning (plus ATG 5 mg/Kg in the setting of unrelated donor, MUD) from 10/2013-06/2015. They received peripheral grafts, CD34+ 7.0×106/kg from siblings (6 patients), 8/8 (9 patients) or 7/8 matched (5 patients) unrelated donors. The historic group consisted of 26 consecutive patients treated with FluBuATG during 2002-2012 for AML (20), MDS (5), MDS related AML (1). Chimerism evaluation in unfractionated bone marrow with STR (short tandem repeat) fragment analysis was performed regularly (on day + 14, + 30, +60, + 90) in both groups. Donor chimerism ≥99% was considered as complete donor chimerism (CDC).Results: The two groups were similar in terms of age, disease phase and risk group, lines of treatment or HCT-CI, except for more MUD in FluTreo. In the FluTreo group, neutrophil engraftment was achieved at day +10 (8-11) and platelet +12 (9-20), with 6 median days of neutropenia. Both groups experienced early engraftment: median time to CDC for both groups was + 30 days (range 12-69 in the Flutreo and 12-205 in the historic group). No significant difference was found between the two groups with respect to CDC on days +14 (30% vs 28%) or +30 (69% vs 57% respectively). Among patients receiving Flutreo 6 experienced CMV reactivation (2 infections), 7 EBV (1 PTLPD) and 1 tuberculosis. No grade III-IV organ associated toxicities were noted. Until last follow-up, 6 patients developed grade ≥II aGVHD and 9 cGVHD. Sixteen patients are alive in CR, while 4 died: 2 aGVHD grade III/IV, 1 cGVHD and 1 disease progression. With a median follow-up of 14 (2-130) for FluBuATG and 8.1 (2-20) months for FluTreo, 1-year disease-free survival was significantly higher in FluTreo (49% vs 88% respectively, p=0.009). Similarly, FluTreo showed a significant advantage in 1-year overall survival (OS) too (39% vs 77% respectively, p=0.006). In multivariate analysis, the regimen (FluBuATG vs FluTreo), age, disease phase, donor, lines of treatment, GVHD and HCT-CI were incorporated. In terms of OS, only the regimen (FluTreo) was recognized as a significantly favorable factor (p=0.029). FluTreo was also significant for superior DFS (p=0.016) along with less lines of treatment pre-transplant (p=0.026). Treatment related mortality (TRM), in univariate analysis, was significantly associated with MDS, time from diagnosis to transplant and previous lines of treatment, but none in multivariate analysis.Conclusions: This treosulfan-based reduced toxicity regimen seems safe and efficacious providing balanced immunosuppression that retains a graft-versus-leukemia effect with myeloablative activity and acceptable toxicity profile. Despite similar patterns of complete chimerisms compared to standard reduced intensity regimens, this regimen favors durable complete chimerism with low relapse rate. Prospective studies with longer follow-up are necessary to establish the advantages of this treosulfan-based regimen that render it a favorable alternative option in patients unfit for conventional regimens. DisclosuresNo relevant conflicts of interest to declare.

The Probability of Invasive Fungal Infection Among Children with Persistent Febrile Neutropenia and Respiratory Viral Infection

▪Febrile neutropenia (FN) is a common complication among children undergoing chemotherapy for hematologic malignancies. A microbial agent is identified in 15–30% of these episodes. Recently, several studies reported a high incidence (25% -60%) of respiratory viral infections (RVI) in children with FN, using RT- PCR analysis. Implementation of routine RVI workup in children with FN was suggested, in order to minimize the overuse of antibiotics.However, data on the incidence of RVI in children with persistent FN (PFN) is meager. In the setting of PFN, invasive fungal infection (IFI) is a major concern.The incidence of IFI among children with hematologic malignancies varies with clinical settings, although most children who present with PFN do not have IFI eventually. Yet, most international guidelines indicate empiric initiation of antifungal therapy after 4-7 days of FN. Alternatively, a “preemptive” approach using currently available diagnostic modalities (CT and serum specific biomarkers) was suggested in adult patients.In children with PFN, however, this workup resulted only in a modest decline in the antifungal treatment rate.Therefore, there is a growing need to enhance diagnostic resolution, in order to stratify pediatric patients according to their risk for IFI, and minimize the overuse of antifungal drugs, imaging, and invasive procedures.To the best of our knowledge, there are no studies comparing the incidence of RVI to that of IFI in the setting of PFN.Based on previous published data, we hypothesized that RV infection is a significant cause of PFN in children with hematologic malignancies, and that IFI is the cause in a minority of cases.We further aimed to investigate whether detection of RVI, as the cause of PFN in these children, would affect their risk of IFI.For that purpose, we analyzed the clinical charts of children (<21 years) with hematologic malignancies who presented to our department during 2007-2013 with PFN (>38oc, for >96 hours and ≤500ANC/µl) and documented PCR results of RV.Patients were considered positive for IFI if they had ‘possible’, ‘probable’ or ‘proven’ infection according to the revised EORTC definition (2008).RVI were detected in nasopharyngeal aspirates using RT-PCR and included: RSV, Influenza A/B, H1N1, Parainfluenza 1/2/3, HMPV, Adenovirus and HHV-6.Additional data included age and gender, specific hematologic malignancy, total number of neutropenia (<500 ANC/µl) days per episode, total number of antibiotic therapy days per episode, bacterial co-infection, anti-fungal prophylaxis, imaging results, BAL/biopsy results and serum biomarkers.A total number of 75 PFN episodes were evaluable, representing 54 patients with ALL (HR n=18; SR n=23), AML (n=6), NHL (n=5) or Hodgkin’s (n=2). Of these, there were 31 episodes with RV-positive infections (41.3%). The most prevalent virus was RSV (29%), followed by Parainfluenza (26%) and Adenovirus (19%).There were 16 possible (21%), 2 probable (2.6%), and 2 proven (2.6%) episodes of IFI. Only in 3 episodes we detected co-infection of IFI (2 possible and 1 probable) and RVI.Multivariate analysis revealed that the total days of neutropenia and antibiotic therapy were independent risk-factors for IFI (p<0.0109; P< 0.0034 respectively). RVI was independently associated with a significant reduced risk for IFI, with an odds ratio of 7.47 (p<0.0082, 95% CI -1.6-50.4). Age, specific hematologic malignancy, bacterial co-infection, and antifungal prophylaxis did not reach significance.Children with PFN and RVI have a significantly lower risk for IFI. This observation may reduce unnecessary imaging and invasive procedures, antifungal treatment, and hospital expanses. Further studies are needed in order to establish whether RV-status can be implemented in the routine workup algorithm of PFN in children with hematologic malignancies. DisclosuresNo relevant conflicts of interest to declare.

Incidence of diarrhea by Clostridium difficile in hematologic patients and hematopoietic stem cell transplantation patients: risk factors for severe forms and death.

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.

Second Bacteremia During Antibiotic Treatment in Children With Acute Myeloid Leukemia: A Report From the Canadian Infections in Acute Myeloid Leukemia Research Group.

The risk of second bacteremia during antibiotic treatment for initial bacteremia is unknown in high-risk populations. Our objectives were to describe the prevalence of second bacteremia during treatment and identify risk factors in children with acute myeloid leukemia (AML). We conducted a retrospective, population-based cohort study that included children and adolescents with de novo, non-M3 AML who were diagnosed and treated between January 1, 1995 and December 31, 2004 at 15 Canadian centers. Patients were monitored for bacteremia during chemotherapy until completion of treatment, hematopoietic stem cell transplantation, relapse, refractory disease, or death. There were 290 episodes of bacteremia occurring in 185 (54.3%) of 341 children. Eighteen (6.2%) had a second bacteremia while receiving antibiotic treatment. Two episodes of second bacteremia were complicated by sepsis; there were no infection-related deaths. Eleven episodes (61.1%) had either an initial Gram-positive and subsequent Gram-negative bacteremia or initial Gram-negative followed by Gram-positive bacteremia. Days receiving corticosteroids (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07-1.12; P < .0001), cumulative dose of corticosteroids (OR, 1.04; 95% CI, 1.00-1.08; P = .035), and days of neutropenia from start of course to initial bacteremia (OR, 1.07; 95% CI, 1.02-1.12; P = .007) were significantly associated with second bacteremia. In pediatric AML, 6% of patients will experience a second bacteremia during antibiotic treatment; duration of corticosteroid exposure and neutropenia are risk factors. These patients remain at high risk for second bacteremia after identification of the initial bacteremia and warrant continued broad-spectrum treatment during profound neutropenia.

Severe infections in children with acute leukemia undergoing intensive chemotherapy can successfully be prevented by ciprofloxacin, voriconazole, or micafungin prophylaxis

The purpose of the current study was to prevent bloodstream infection and invasive fungal infection (IFI) by administering prophylactic antibiotic and antifungal agents during intensive chemotherapy in patients being treated for acute leukemia. Prophylaxis treatment was administered during intensive chemotherapy in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) from January 1, 2010 to December 31, 2012. Oral ciprofloxacin (at a dose of 300 mg/m(2) /12 hours) was administered after chemotherapy when a patient with AML or ALL became neutropenic and > 7 days of neutropenia was expected. Voriconazole (at a dose of 4 mg/kg/12 hours) was initiated at the onset of neutropenia in patients with AML and after 7 days of neutropenia in patients with ALL. Micafungin (at a dose of 2 mg/kg/day) was substituted for voriconazole when patients with ALL received vincristine. Prophylaxis treatment was discontinued when the absolute neutrophil count recovered to > 100/μL. All episodes of bloodstream infection, IFI, febrile neutropenia, and intensive care unit stays related to severe infection occurring between January 1, 2005 and December 31, 2012 were recorded. During the preprophylaxis period, 62 children with ALL and 24 children with AML experienced a total of 44 episodes of bloodstream infection and 22 episodes of IFI. Seven patients died of severe infection. In contrast, in the prophylaxis period, 10 episodes of bloodstream infection occurred and no IFIs were reported to occur in 51 patients with ALL and 14 patients with AML. Moreover, no patient died of severe infection. Episodes of febrile neutropenia and intensive care unit stay were significantly reduced during the prophylaxis period. Prophylaxis with ciprofloxacin and voriconazole or micafungin was found to reduce the rates of bloodstream infection and IFI in children with acute leukemia undergoing intensive chemotherapy.

Second Bacteremia During Antibiotic Treatment In Children With Acute Myeloid Leukemia: A Report From The Canadian Infections In AML Research Group

Abstract Background The risk of second bacteremia during antibiotic treatment for initial bacteremia is unknown in high-risk populations. Objectives were to describe the prevalence of second bacteremia during treatment and identify risk factors in children with acute myeloid leukemia (AML). Methods We conducted a retrospective, population-based cohort study that included children and adolescents with de novo, non-M3 AML who were diagnosed and treated between January 1, 1995 and December 31, 2004 at 15 Canadian centers. Patients were monitored for bacteremia during chemotherapy until completion of treatment, hematopoietic stem cell transplantation, relapse, refractory disease, or death. Results There were 290 episodes of bacteremia occurring in 185 (54.3%) of 341 children. Eighteen (6.2%) had a second bacteremia while receiving antibiotic treatment. Two episodes of second bacteremia were complicated by sepsis; there were no infection-related deaths. Eleven episodes (61.1%) had either an initial Gram-positive and subsequent Gram-negative bacteremia or initial Gram-negative followed by Gram-positive bacteremia. Days receiving corticosteroids (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.07-1.12; P&lt;0.0001), cumulative dose of corticosteroids (OR 1.04, 95% CI 1.00-1.08; P=0.035) and days of neutropenia from start of course to initial bacteremia (OR 1.07, 95% CI 1.02-1.12; P=0.007) were significantly associated with second bacteremia. Conclusion In pediatric AML, 6% will experience a second bacteremia during antibiotic treatment; duration of corticosteroid exposure and neutropenia are risk factors. These patients remain at high risk for second bacteremia after identification of the initial bacteremia and warrant continued broad-spectrum treatment during profound neutropenia. Abbreviations CONS: coagulase negative Staphylococcus ; VGS: viridans group Streptococcus; Amp: ampicillin; Cz: ceftazidime; Cef: cefotaxime; Cipro: ciprofloxacin; Clin: clindamycin; Clox: cloxacillin; G: gentamicin; Metro: metronidazole; Mero: meropenem; O: oxacillin; Pip: piperacillin; Ta: piperacillin/tazobactam; Tm:ticarcillin/clavulanate; To: tobramycin; V: vancomycin. Disclosures: No relevant conflicts of interest to declare.

Epidemiology Of Invasive Aspergillosis (IA) During Induction Therapy In Adults With Acute Lymphoblastic Leukemia (ALL): A Graall-2005 Study

BackgroundIA is a major cause of morbidity and mortality for patients with hematological malignancies and has been mainly reported in patients with acute myeloblastic leukemia (AML) and stem cell transplantation. Much less is known about the role of IA during the treatment of lymphoproliferative diseases like ALL. Here, we retrospectively evaluated the characteristics of patients and the incidence of IA occurring during the induction course in adult ALL patients enrolled in the GRAALL-2005 trial. MethodsWe collected the data of 36 patients with IA during induction chemotherapy. All were included between May 2006 and October 2012 in the multicentric GRAALL-2005 phase III trial. According to ALL characteristics, these patients were treated in 3 different substudies: GRAALL, GRAALL-Rituximab (GRAALL-R) for CD20+ ALL, GRAAPH for Philadelphia (Ph) chromosome-positive ALL. IA was defined retrospectively using the EORTC modified criteria (De Pauw, CID 2008). ResultsAmong the 969 patients enrolled, 36 (3.7%) developed IA during induction therapy. The median age was 30 years for all patients receiving induction and 47 years (range, 18 to 59) for patients with IA. We observed 18 IA (3%) by the GRAALL protocol (593 patients enrolled), 16 (8.3%) by the GRAALL-R protocol (191 patients enrolled), and 2 (0.7%) by the GRAAPH protocol (270 patients enrolled). In the GRAALL-R protocol, IA was diagnosed in 6 patients randomly assigned to receive rituximab and in 10 patients treated in the control group. The median time between first day of induction therapy and IA diagnosis was 20 days (range, -2 to 71). The median time between the first day of neutropenia and IA diagnosis was 18 days (range, 0 to 76). At the time of IA diagnosis, 13 patients were hospitalized in laminar airflow rooms, 10 patients in rooms with overpressure, 1 patient in a room with high-efficiency particulate filter, 5 patients in conventional rooms, 1 patient received home care and the type of hospitalization was unknown for the 6 remaining patients. Four patients with IA (11%) had received antifungal drug for invasive fungal infection (IFI) prophylaxis: one patient received fluconazole, one received caspofungin, and two received liposomal amphotericin B. All patients with IA presented pulmonary symptoms associated with a sinusal or cutaneous localization in 1 and 2 patients respectively. The diagnosis of IA was classified as possible in 7 episodes (19 %), probable in 22 episodes (61%), proven in 4 episodes (11%), and indeterminate in the remaining 3 episodes. Detection of Aspergillus antigen in serum by latex agglutination was positive in 24 cases (67%). Chest CT scans were taken for 33 patients (92%): nodules were found in 19 patients, halo sign in 20 patients, and “air crescent sign” in 1 patient. Bronchoalveolar lavage was performed in 11 patients (31%): culture was positive in 7 of them and Aspergillus antigen was positive in 2 of them. Biopsies where positive in 4 cases: in pulmonary biopsy in 3 patients and in cutaneous biopsy in 1 patient. Of all the Aspergillus isolates identified to the species level, Aspergillus fumigatus was isolated from 4 patients and Aspergillus flavus from 1 patient. Overall and IA-attributable 12-week mortality was 8 (0.8%) and 6 (16.7%) patients respectively. ConclusionIA is less frequently observed during induction therapy in adult ALL as compared to adult AML patients. However, the attributable mortality appears to be high in these patients. They are as at risk patients for IA and should be included in prophylactic and empirical antifungal clinical trials. Disclosures:No relevant conflicts of interest to declare.

Efficacy and Safety of Micafungin for Febrile Neutropenia in Pediatric Patients With Hematological Malignancies

Invasive fungal infections are a major cause of infectious mortality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation. However, little is known about the efficacy and safety of micafungin (MCFG), an echinocandin antifungal agent, in pediatric patients with febrile neutropenia (FN). This study was conducted as a prospective multicenter trial to evaluate the efficacy and safety of MCFG for FN in pediatric patients with hematological diseases. Efficacy was assessed based on the response to the 5 composite endpoints established by Walsh and colleagues in addition to body temperature and C-reactive protein values. Thirty episodes of FN were enrolled in the study. The median dose and duration of MCFG treatment were 3.0 mg/kg/d and 13.5 days, respectively. Using the criteria of Walsh and colleagues, MCFG was effective in 56.7% of the patients. No breakthrough invasive fungal infection occurred during MCFG treatment. Body temperatures on the last day of neutropenia during administration of MCFG and on the last day of MCFG therapy and C-reactive protein values after administration of MCFG were significantly lower than on the day MCFG therapy was started. Adverse effects in the form of mild liver dysfunction were seen in only 2 patients. MCFG is a very effective and safe antifungal drug for FN in children. Physicians should administer MCFG early in febrile episode in patients in whom first-line antibiotics are not effective in treating FN.

Health care-associated infections in hematology-oncology patients with neutropenia: A method of surveillance

We present a prospective method of surveillance of health care-associated infection in hematology-oncology inpatients with neutropenia. Incidence rates were calculated on the basis of the number of hospitalized patients, the duration of hospital stay (in days), the number of days of neutropenia, and (in cases of central line-associated blood stream infection) the number of central line-days. We detected 11.4 and 66.4 episodes of febrile neutropenia per 1,000 hospital-days and per 1,000 days of neutropenia, respectively. The incidence of central line-associated blood stream infection was 2.6 per 1,000 central line-days. Gram-negative bacteria were the most prevalent pathogens. Efforts should be made to monitor infection rates on hematology-oncology wards.

Cost Effectiveness of Pegfilgrastim Versus Filgrastim After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Lymphoma and Myeloma

Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet. We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100±10days from transplant. The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital's point of view and are expressed in 2009euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann-Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5×10(9)/L and temperature ≥38°C), duration of neutropenia (ANC <1.0×10(9)/L and ANC <0.5×10(9)/L), duration of thrombopenia (platelets <50×10(9)/L and <20×10(9)/L), and days with a temperature ≥38°C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method. 151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n=74) was <euro>25,024 (SD 9,945). That in the filgrastim arm (n=76) was <euro>28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0×10(9)/L) avoided, days of thrombopenia (platelets <20×10(9)/L) avoided, and days with temperature ≥38°C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5×10(9)/L avoided and the number of days with platelets <50.0×10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67% for febrile neutropenia, 86% for neutropenia (ANC <1.0×10(9)/L), 59% for thrombopenia (platelets <20×10(9)/L), 86% for temperature ≥38°C, 32% for neutropenia (ANC <0.5×10(9)/L), and 43% for thrombopenia (platelets <50×10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5×10(9)/L) is 5%. This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.

Risk factors and outcomes of Candida krusei bloodstream infection: A matched, case-control study

To investigate the risk factors and outcomes associated with Candida krusei bloodstream. We performed a case control study of patients with C. krusei bloodstream infection at the University of Pennsylvania from 1982 to 2010. Controls were without candidemia, and matched to cases on duration of hospitalization and underlying disease. We enrolled 34 cases and 114 matched controls. Most subjects (62%) had hematologic malignancies. In the multivariate model, including a priori the duration of fluconazole use (OR 1.06; 95% CI 1.00, 1.11) and days of neutropenia (OR 1.01; 95% CI 0.98, 1.13), risk factors associated with C. krusei bloodstream infection were splenectomy (OR 11.66; 95% CI 1.04, 130.64), and exposure to antimicrobials with anaerobic activity (OR 5.74; 95% CI 1.76, 18.67). Outcomes of infected patients were poor. Only 32% of case patients survived to hospital discharge, compared to 89% of controls. For 48% death was attributed to C. krusei infection. C. krusei bloodstream infection occurs most commonly in neutropenic patients with hematologic malignancy. The association with prior fluconazole exposure is less marked than previously described. Splenectomy and the receipt of antimicrobials with anaerobic activity are significant risk factors. The outcome of infected patients remains poor, despite appropriate antifungal therapy.

Healthcare-associated infection in hematopoietic stem cell transplantation patients: risk factors and impact on outcome

The objective of this study was to analyze the incidence of and risk factors for healthcare-associated infections (HAI) among hematopoietic stem cell transplantation (HSCT) patients, and the impact of such infections on mortality during hospitalization. We conducted a 9-year (2001-2009) retrospective cohort study including patients submitted to HSCT at a reference center in São Paulo, Brazil. The incidence of HAI was calculated using days of neutropenia as the denominator. Data were analyzed using EpiInfo 3.5.1. Over the 9-year period there were 429 neutropenic HSCT patients, with a total of 6816 days of neutropenia. Bloodstream infections (BSI) were the most frequent infection, presenting in 80 (18.6%) patients, with an incidence of 11.7 per 1000 days of neutropenia. Most bacteremia was due to Gram-negative bacteria: 43 (53.8%) cases were caused by Gram-negative species, while 33 (41.2%) were caused by Gram-positive species, and four (5%) by fungal species. Independent risk factors associated with HAI were prolonged neutropenia (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.10) and duration of fever (OR 1.20, 95% CI 1.12-1.30). Risk factors associated with death in multivariate analyses were age (OR 1.02, 95% CI 1.01-1.43), being submitted to an allogeneic transplant (OR 3.08, 95% CI 1.68-5.56), a microbiologically documented infection (OR 2.96, 95% CI 1.87-4.6), invasive aspergillosis disease (OR 2.21, 95% CI 1.1-4.3), and acute leukemias (OR 2.24, 95% CI 1.3-3.6). BSI was the most frequent HAI, and there was a predominance of Gram-negative microorganisms. Independent risk factors associated with HAI were duration of neutropenia and fever, and the risk factors for a poor outcome were older age, type of transplant (allogeneic), the presence of a microbiologically documented infection, invasive aspergillosis, and acute leukemia. Further prospective studies with larger numbers of patients may confirm the role of these risk factors for a poor clinical outcome and death in this transplant population.

Retrospective Review of Invasive Fungal Disease in a Cohort of Patients with Acute Leukemia

Abstract 4265 Background:Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients with acute leukemia (AL). Fluconazole has an established role for prophylaxis in the setting of allogeneic hematopoietic stem cell transplant (AHSCT), and possibly in the setting of acute leukemia. More recently, posaconazole has been shown to reduce the incidence of IFD and mortality in AHSCT recipients, and in patients undergoing chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, with increasing use of broader-spectrum antifungal agents, there are concerns regarding breakthrough infections with resistant organisms. Objectives:The first goal of this study is to define the epidemiology of IFD in all patients with acute leukemia, treated at one academic center (The Ottawa Hospital). The second goal is to identify risk factors, which could stratify patients into a very high risk category for the development of IFD. We hope to identify a subset of patients who would benefit from prophylaxis with broader-spectrum antifungal agents. Methods:We performed a retrospective study of adult patients with acute leukemia (including AML, acute lymphoblastic leukemia (ALL), high-grade MDS and blast-phase CML) treated at our institution between May 2009 and April 2011. Patients at all stages of treatment were included. All patients treated with antifungal agents were identified through our pharmacy database. Computerized medical records were reviewed for baseline demographics (age, gender, occupation, diagnosis, days of neutropenia and comorbidities), as well as treatment-related variables (chemotherapy regimen, conditioning regimen, date of AHSCT, response to treatment and presence of GVHD). Imaging, microbiology and biopsy results were also collected. Proven and probable IFD were defined as per the 2008 EORTC/MSG revised criteria. Patient characteristics were compared using Fisher's exact test. Results:We identified 89 inpatient encounters. Primary diagnosis was AML in 58, high-grade MDS in 15, ALL in 12, blast-phase CML in 3 and PCL in 1 patient. 42 patients were undergoing induction chemotherapy and 10 were undergoing consolidation. 30 patients were post-AHSCT. Contrary to prior studies, all patients were on fluconazole prophylaxis. Out of these 89 encounters, 8 patients (9%) were diagnosed with proven or probable IFD, 12 (13%) met criteria for possible IFD, and the rest (69/89 or 78%) did not meet criteria for IFD. There were 5 probable cases of pulmonary aspergillosis, 1 proven case of hepatic aspergillosis, and 2 proven cases of zygomycosis (1 disseminated and 1 CNS).In terms of risk factors, in our initial analysis, median age was higher in patients with IFD than in patients without (62 vs. 57), though this difference did not reach statistical significance (p = 0.46). There was no difference in the development of IFD based on gender, occupation, days of neutropenia or comorbidities. Although this did not reach statistical significance, almost all patients with IFD had an underlying diagnosis of AML (7/8). In addition, no patients were diagnosed with IFD during consolidation therapy. This is consistent with prior studies. We were not able to assess transplant-related variables, given that only one IFD was diagnosed in a post-AHSCT patient.Overall mortality at 30 days post-admission was significantly higher in the IFD group (6/8 vs. 28/81, p = 0.05). However, only 1 death was directly attributable to the IFD. Otherwise, 3/8 patients with IFD died of refractory leukemia (1 post-AHSCT), 1/8 died of leukemia, 1/8 died of multiorgan failure (not clearly related to IFD), 1/8 survived hepatic aspergillosis and 1/8 survived disseminated mucormycosis. Conclusions:Though limited by sample size, our study indicates that older patients, patients with AML, patients undergoing induction chemotherapy and patients with refractory leukemia may be at highest risk for IFD. In addition, in our cohort, almost all patients with IFD died of their underlying leukemia, while being treated for IFD. It is not clear at this time, but suggestive, that the diagnosis of IFD delayed or interfered with the ongoing treatment plan for some of these patients, possibly contributing to their treatment failure. Therefore, the use of novel antifungal agents would be favored in this group to avoid interruption of leukemia treatment. Further study of this group is currently underway. Disclosures:No relevant conflicts of interest to declare.

Comparison of Clostridium Difficile Associated Diarrhea Detection by Enzyme Linked Immunosorbent Assay (EIA) and Polymerase Chain Reaction (PCR) in Autologous Hematopoietic Stem Cell Transplant (AHSCT) Recipients

Abstract 4739 Background:Diarrhea is a frequent complication of autologous hematopoietic stem cell transplantation and is a common cause of morbidity. Clostridium difficile associated diarrhea (CDAD) is the most common cause of nosocomial infections. Detection of CDAD is widely performed using enzyme linked immunosorbent assay (EIA) to C. difficile toxins A and B because of its technical ease of use and rapid results. The sensitivity of EIA is 60%, but the sensitivity increases with repeated testing. Recently, detection of CDAD by Polymerase Chain Reaction (PCR) methodology has resulted in rapid detection of amplified C. difficile toxin (CDT) B chromosomal material and has been shown to be more sensitive than EIA in patients suspected of CDAD; however, no comparison of the two methodologies has been performed in recipients of an autologous hematopoietic AHSCT. Methods:This retrospective analysis of AHSCT recipients at our institution evaluates the incidence of CDAD when using either EIA or PCR. CDAD was assessed at the onset of diarrhea in both cohorts. The time period of interest was from 7 days prior to transplantation to 30 days posttransplanation. In the EIA cohort, three consecutive liquid stools were tested for the presence of CDT A and B by EIA. In the PCR cohort, only one liquid stool was sent for sampling. Our institution adopted PCR methodology on 1 February 2010. Demographic and clinical information were collected to assess CDAD risk. Successful treatment of CDAD was defined as resolution of diarrhea within seven days. Previously published data from our institution have shown the incidence of CDAD to be 15% when using EIA methodology. Nominal data were analyzed by Fisher's Exact Test and continuous data were analyzed by Student's T-Test. Results:A total of 159 patients were screened; and 16 patients were excluded because they did not have a CDAD test performed. Seventy-three were included in the EIA cohort and 69 were included in the PCR cohort. Clinical characteristics were similar between the groups. Known risk factors for CDAD including days in the hospital, days of neutropenia, and days of prophylactic and intravenous antibiotics used were similar between the cohorts. The incidence of a positive CDAD test was higher in the EIA cohort compared to the PCR cohort (18% vs. 7% [p = 0.049]). The duration of diarrhea was longer in the EIA cohort as compared to the PCR cohort (7.3 days vs. 5.5 days [0.016]). Of the three consecutive EIA tests sent, the first was positive only 30% (4/13) of the time. Metronidazole was the first-line agent used in all cases. Response to therapy was poor in both the EIA and PCR cohorts with rates of 30% and 20%, respectively. No fatalities occurred in either group as a result of CDAD. Conclusion:The incidence of diarrhea was significantly shorter in the PCR cohort as compared to the EIA cohort. The duration of diarrhea was significantly shorter in the PCR group as compared to the EIA cohort. It is possible that repeated testing for CDAD by EIA decreases the specificity of the test or that the EIA is detecting a non-toxigenic C. difficile enterotoxin. Because our patient population has additional causes of diarrhea including mucosal irritation caused by chemotherapy, additional studies are needed to discern the discrepancies between both methodologies.EIA Cohort (n=73)PCR Cohort (n=69)P valueAge (median, years)61600.163Race (n,%)36 (49)38 (55)0.521Caucasion19 (26)20 (29)African American17 (23)11 (16)Hispanic1 (1)0 (0)OtherMale (n,%)71 (97)64 (93)0.265Karnofsky Performance Status (median,%)90900.932Disease (n,%)56 (77)45 (65)0.625Myeloma15 (20)21 (30)Lymphoma2 (3)3 (5)OtherCDAD (n,%)13 (18)5 (7)0.049Diarrhea Duration (mean, days)7.35.50.016 (−3.32 to −0.16)CDAD treatment response (n,%)4 (30)1 (20)0.568Days of Neutropenia (mean, days)76.70.553 (−1.01 to 0.54)Days of oral antibiotics (mean, days)4.54.30.774 (−1.04 to 0.77)Days of IV antibiotics (mean, days)7.35.50.170 (−4.33 to 0.77) Disclosures:No relevant conflicts of interest to declare.

Performance of the new Platelia Candida Plus assays for the diagnosis of invasive Candida infection in patients undergoing myeloablative therapy

The performance of the new Platelia Candida Antigen Plus (Ag Plus) and Antibody Plus (Ab Plus) assays (Biorad Laboratories, France) was evaluated using a collection of serum samples obtained from 21 patients with microbiologically proven invasive candidiasis and 30 control patients who were being treated with myeloablative chemotherapy, and the data compared with that obtained with the earlier version of the Platelia Candida assays (Ag and Ab), and 1,3-ß-D-glucan (BG) detection systems. The sensitivity of the Ag Plus and Ab Plus assays in the per patient analysis ranged from 55-70% and from 30-64% for patients with less than 15 days of neutropenia and more than 15 days of neutropenia, respectively. Sensitivity and time to detection of these new assays was not significantly better than of the conventional Platelia Candida tests. However, the specificity of the Ag-Plus assay was reduced by approximately 50% as compared to the Ag assay. Logistic regression analysis showed that this was probably due to the fact that circulating mannan was also being detected by the Ag Plus assay in patients with superficial candidiasis. Further studies are needed to confirm our results and to determine the place of the Platelia Ag Plus and Ab Plus assays in the management of haematology patients at risk for Candida infections.

Empirical Vs. Prophylactic Antifungal Strategies: Comparison of Effectiveness In High Risk AML Patients at a Tertiary Cancer Center

AbstractAbstract 1729 Objectives:Invasive fungal infections (IFI) remain a major threat for patients with acute myelogenious leukemia (AML). Since the publication of two landmark studies, which demonstrated a reduction in morbidity and mortality from IFI in high risk patients through prophylaxis with posaconazole, guidelines have recommend routine prophylaxis with posaconazole during induction chemotherapy. However, prompt empirical or pre-emptive therapy strategies are still commonly used alternatives. Real life data about posaconazole prophylaxis are scarce and potential overtreatment, increasing costs and development of resistant fungi are of concern. We therefore compared effectiveness of empirical and prophylactic antifungal strategies at a tertiary cancer center during a phase of intensive building (re-) construction Methods:104 patients (pts.) with AML treated between January 2005 and February 2009 were retrospectively evaluated. Each induction chemotherapy or consolidation therapy with neutropenia >=10 days was counted as an episode (n=222). Patients were stratified according to their antifungal approach: primary prophylaxis (n=35, 51 episodes; group 1), empirical therapy (n=63, 111 indices; group 2), secondary prophylaxis (n=41, 60 episodes; group 3, which comprised of patients from groups 1 and 2). Group 1 received posaconazole 3 × 200 mg p.o.; group 2 received topical polyene prophylaxis and empirical treatment with voriconazole or fluconazole. Patients in group 3 received either voriconazole, posaconazole, fluconazole or intraconazole. Results:Demographics, AML subtypes, co-morbidities and neutropenic days (median = 13) were comparable in all three groups; no patient received G-CSF support. Logistic regression analysis revealed days of neutropenia, performance status, use of antibiotics and secondary AML as risk factors for development of IFI, while primary prophylaxis reduced the risk for possible/probable/proven IFI by 86,7% compared to empirical therapy (p=0.001). Incidences of probable/proven IFI were 3% in group 1, 29% in group 2 and 7% in group 3 (p=0.001) and 17%, 69% and 37% (p<0.001) when possible IFIs were included. Mortality during observation period was similar (4%, 6,4%, 7%, NS). Also similar were isolated pathogens, additional antifungals, change of antibiotics, days at intensive care unit (ICU). Bacterial infections were similiar in all groups except for pneumonia and GI-tract infections being significantly higher in pts with empirical antifungal therapy. Side effects were also slightly higher in this group (8% vs 2% and 5%, NS). Days of hospitalization, antifungal, antibiotic, and antiviral costs were comparable, while imaging costs were significantly higher in group 2 (p=0.006). Conclusion:Posaconazole prophylaxis significantly reduces incidences of IFI in high risk AML patients and leads to a reduction of costs for imaging studies, with a minimal overall reduction of costs for inpatients. Additionally, infectious complications such as pneumonia and GI-tract infections are also reduced, while mortality rates, days of hospitalization, anti-infective use or duration are not reduced. Accordingly, in areas/surroundings with high rates of fungal infections (e.g. due to intensive building (re-)construction), primary prophylaxis with posaconazole is recommended. Disclosures:Brummendorf:Pfizer: Membership on an entity's Board of Directors or advisory committees. Panse:Gilead: Honoraria; Schering-Plough: Honoraria; MSD: Travel Grant.

Successful Control of Preexistent Active Infection by Granulocyte Transfusions During Conditioning Induced Cytopenia In Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Stem Cell Transplant

AbstractAbstract 1329Chronic granulomatous disease (CGD) is a congenital disorder resulting from decreased or absent oxidase production by neutrophils. As a result, patients with CGD are prone to bacterial and fungal infections and have a shortened life expectancy. Hematopoietic stem cell transplantation (HSCT) can be curative, and patients are increasingly referred for transplant due to an ongoing infection not amenable to cure using standard treatments. The use of granulocyte transfusions has been described in patients undergoing transplant with an underlying infection at the time of conditioning, but reports are limited to single cases. We describe here the effects of granulocyte transfusions in four patients undergoing either an HLA matched sibling or unrelated donor HSCT, using an alemtuzumab containing regimen and sirolimus as GVHD prophylaxis. Age of the patients was 6 to 25 (mean 11.5) yrs, and weight was 15.3 to 54 (mean 27.5) kg. Three of the patients had persistent Aspergillus infection involving the spine, lung, and/or brain despite long term combination antifungal therapy including a triazole, echinocandin and/or amphotericin. The fourth patient had an Actinomyces pneumonia progressive on combination antibacterial treatment. None of the patients had detectable HLA antibodies prior to the transfusions, and none received G-CSF post-transplant. The granulocytes were started on the anticipated day of neutropenia after conditioning and graft infusion and continued until evidence of graft recovery. Volunteer community donors underwent mobilization with dexamethasone 8 mg PO plus G-CSF 480 mcg SC, followed the next day by a 7-liter leukapheresis procedure (Spectra) using Tricitrasol/Hetastarch (Hespan) as the anticoagulant/sedimenting solution. Patients received a mean of 4.5 transfusions each, with three patients receiving biweekly transfusions and one receiving transfusions three times a week. The mean number of granulocytes per component transfused was 6.17 × 10e10 (range 4.0–9.12). This resulted in a mean of 2.78 × 10e9 granulocytes transfused per kg recipient weight (range 0.76–4.48). All patients tolerated the infusions well, without respiratory symptoms. The mean increase in absolute neutrophil count posttransfusion was 1.95 × 10e3/uL (range 0.5–4.61), although the timing of collection of the blood count samples was variable for each transfusion. Using a dihydrorhodamine (DHR) fluorescence based assay we were able to track the presence of oxidase positive cells to help differentiate transfused donor from residual host cells. DHR assays were performed before and after every transfusion in one patient. The number of DHR positive cells prior to infusion was 0–1.4% with a rise to 68.2% 24 hours after transfusion. 24.5% oxidase positive cells were still detectable almost 72 hours after transfusion, just prior to the next transfusion. One product required sedimentation for ABO incompatibility. The mean time to engraftment was 22 days and did not differ in patients with CGD receiving the same transplant regimen with (n=4) or without (n=6) peri-transplant granulocyte transfusions (30 days). Although all four patients had infectious processes not responding to standard antimicrobial therapy prior to transplant, there was no evidence of progressive infection during the period of neutropenia. Imaging studies of the brain, lung and/or spine suggested improvement in the infectious process in all four patients, although the timing of the scans made assessments inconclusive. Our prior experience with granulocyte transfusions in patients with CGD not undergoing transplant is that the cells do not persist in the circulation longer than 24 hours. Higher cell doses per kg in our four patients may have contributed to the sustained detection of transfused circulating cells, particularly as three of the patients weighed less than 21 kg. Peri-transplant immune suppression may also have facilitated the longer circulation time of the cells. We conclude that community-donor granulocyte transfusions are well tolerated in non-alloimmunized CGD patients undergoing HSCT, do not impact engraftment, are logistically feasible, and may provide a therapeutic bridge for patients with an underlying infection during a prescribed period of neutropenia, thus decreasing transplantation risk for such patients. Disclosures:No relevant conflicts of interest to declare.