scholarly journals Incidence of Breakthrough Invasive Fungal Infections after Posaconazole Prophylaxis in Allogeneic Stem Cell Transplant Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5695-5695 ◽  
Author(s):  
Rayaz Ahmed ◽  
Sanghmitra Thakur ◽  
Jyotsna Kapoor ◽  
Narendra Agrawal ◽  
Pallavi Mehta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Febrile Neutropenia ◽  
Bacterial Infection ◽  
Fungal Infection ◽  
Stem Cell Transplant ◽  
Pulmonary Complications ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Single Centre ◽  
Significant Difference

Abstract Background - Invasive fungal infection (IFI) is a complication found in most of the allogeneic stem cell transplant (AlloSCT) recipients leading to high number of morbidity and mortality. Posaconazole, a broad spectrum, second generation triazole compound with antifungal activity, was approved by the FDA for prophylactic use against invasive Aspergillus and Candida infections in immunocompromised patients. The aim of this retrospective observational single centre study is to investigate the incidence of IFI and to determine the various risk factors for IFI in patients within 30 days of AlloSCT who had received posaconazoleprophylaxis in Indian subcontinent. Methods - This study includes the data of all adult patients (>18 years) without history of fungal infection who underwent AlloSCT at the Rajiv Gandhi Cancer Institute and Research Centre- tertiary cancer care center, New Delhi, between January 2015 and December 2017, and received antifungal prophylactic therapy with thrice daily posaconazole in the form of syrup since day +5 of AlloSCT till the antifungal therapy is changed to Amphotericin or Caspofungin for empirical or probable/ possible/proven IFI. All IFI's were classified in accordance with EORTC/MSG criteria into possible, probable or proven IFI. Statistical analyses were performed using SPSS version 21 (IBM, Armonk, NY, USA). Results - During the study period, 50 patients were found to be eligible out of 181. The median(range) of eligible patients was 37 (18-58) years with a male to female ratio of 2.6 :1 (Table 1). Ninety six percent of patients achieved engraftment at a median of 15(11-30) days. Within 30 days of AlloSCT, 78% patients developed prolonged neutropenia (neutropenia for more than 7 days), while 86% patients developed febrile neutropenia . Mucositis, VOD, GVHD, pulmonary complications within 30 days developed in 56%, 6%,8%, and 16% of patients respectively. Bacterial infection and CMV reactivation within 30 days developed in 62% and 20% of patients respectively. Incidence of breakthrough IFI was 10% (n=5) of patients [possible IFI= 60% (n=3), probable IFI= 40% (n=2)], which developed at a median of 17 (9-29) days. Antifungal therapy was changed in 15 patients (30%) because of oral and abdominal mucositis, emperical treatment for febrile neutropenia, TRALI (Acute lung injury), and breakthrough IFI in 5 (10%), 4 (8%), 1 (2%) and5 (10%)patients respectively.IFI resolved in 4 patients (80%), while 1 patient expired due to regimen related toxicity (10%). After 30 days of AlloSCT, 94% of patients were alive, while 6% (n=3) patients expired because of bacterial infection (n=1) and regimen related toxicity (n =2). At a median follow up of 337 (32-1139) days, estimated 2-year Overall Survival (OS) is 56%. IFI did not had any significant difference on the OS and Event Free Survival (EFS). On univariate analysis, no significant difference was found in the development of IFI on the basis of sex mismatched, blood group mismatched, related transplants, matched transplants, conditioning regimen (Myeloablative + reduced intensity vs non myeloablative), presence of prolonged neutropenia, pulmonary complications, hemorrhagic cystitis, acute GVHD ( grade II-IV), mucositis. Bacterial infection within 30 days was found to have a trend towards development of IFI (p=0.06). Conclusion - Results from this retrospective analysis from a single centre showed the lesser incidence of IFI after posaconazole prophylaxis derived from a small sample size within 30 days of AlloSCT. Therefore, we may conclude that posaconazole prophylaxis may serve as an antifungal prophylactic choice for alloSCT recipients without prior fungal infection. Incidence of breakthrough IFI reported here are similar to that reported in comparative studies of fluconazole and posaconazole prophylaxis in alloSCT recipients. Disclosures No relevant conflicts of interest to declare.

Conditioning with Fludarabine, Busulfan, and ATG Prior to Reduced-Intensity Allogeneic Stem Cell Transplant for CLL Is Associated with a Low Incidence of Acute Graft-Versus-Host Disease.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4568-4568
Author(s):  
Samantha M. Jaglowski ◽  
Diane Scholl ◽  
Patrick Elder ◽  
Thomas S. Lin ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Graft Versus Host ◽  
Significant Difference ◽  
Reduced Intensity ◽  
Count Recovery

Abstract Abstract 4568 Introduction: Allogeneic stem cell transplant (SCT) is the only potentially curative treatment available for CLL. While transplant-related mortality has decreased with use of reduced-intensity conditioning (RIC) regimens, acute and chronic graft-versus-host-disease (GVHD) remain important causes of morbidity and mortality, with up to 50% of patients developing chronic GVHD (cGVHD). While the optimal way to combat this has not been established, in vitro T cell depletion with ATG or alemtuzumab has been employed to attempt to lessen its incidence. Herein, we report our institutional experience with each of these agents. Patients and methods: Information on all patients who underwent RIC allogeneic SCT at Ohio State from January 1, 2002 to June 29, 2010 was obtained following approval from the ORRP. Data collected by the transplant coordinators was correlated with data in our electronic databases. Comparative statistics were performed using the Fisher exact test and all p-values are two-sided. Results: Between January 1, 2002 and June 29, 2010, 50 patients with CLL/SLL underwent RIC allogeneic SCT at Ohio State. Pretransplant characteristics are listed in Table 1. Thirty patients received fludarabine, busulfan, and ATG (FBA) as a preparative regimen, and 8 patients received alemtuzumab, fludarabine, and TBI (Cam/Flu/TBI). Another 6 patients received fludarabine and busulfan, 4 received fludarabine and cyclophosphamide, one received pentostatin, fludarabine, and ATG, and the patient who had a cord blood transplant received fludarabine, cyclophosphamide, TBI, and ATG. The breakdown of characteristics between patients who received FBA and Cam/Flu/TBI is also provided in Table 1. None of the characteristics were statistically different. Time to count recovery is provided in Table 2. There was not a statistically significant difference in the time to count recovery between FBA and Cam/Flu/TBI. Patients who received Cam/Flu/TBI received significantly more DLIs; patients who received FBA have not required any DLIs. Incidence of acute and chronic GVHD is provided in Table 3. There was not a statistically significant difference in rates or grades of aGVHD, but patients who received Cam/Flu/TBI were more likely to develop extensive cGVHD. Conclusions: While patients who received Cam/Flu/TBI were more likely to receive DLI, these were all done to treat disease recurrence, reflecting changes in group practice over time. There were no failures to engraft with FBA, and while not statistically significant in comparison to Cam/Flu/TBI, only 10% of patients developed grade 3 or 4 aGVHD. All of the patients who received Cam/Flu/TBI and developed cGVHD developed extensive disease. While the Cam/Flu/TBI sample is small, the FBA patients appear to fare no worse in terms of count recovery and development of GVHD without exposure to TBI, and this has become our institutional practice for patients with CLL. Disclosures: Lin: GlaxoSmithKline: Consultancy, Employment.

scholarly journals 2666. De-escalation of Broad-Spectrum Antibiotics in Hematopoietic Stem Cell Transplant Patients During Initial Episode of Febrile Neutropenia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S934-S934
Author(s):  
Lindsey Rearigh ◽  
Erica J Stohs ◽  
Alison Freifeld ◽  
Andrea Zimmer
Keyword(s):  
Stem Cell ◽  
Febrile Neutropenia ◽  
Hematopoietic Stem Cell ◽  
Broad Spectrum ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Broad Spectrum Antibiotics ◽  
Significant Difference

Abstract Background Febrile neutropenia (FN) is a common and serious complication in patients undergoing hematopoietic stem cell transplant (HSCT). Typically, broad-spectrum antibiotics (BSA) are promptly initiated with controversy on timing of de-escalation. ECIL 2013 guidelines suggest de-escalation after 72 hours if the patient is infection free and afebrile for at least 48 hours. Conversely, the 2011 IDSA recommends continuing BSA in patients who defervesce until absolute neutrophil count (ANC) recovery. In 2014, our center’s practice changed to early de-escalation and we sought to compare outcomes between the two practices. Methods We retrospectively analyzed patients who underwent a HSCT in 2013 and 2017 with an episode of FN and negative infectious work up. The standard care group (SCG) were continued on BSA until ANC recovery. The early de-escalation group (EDG) de-escalated to fluoroquinolone prophylaxis at least 24 hours prior to ANC recovery after the patient was fever free for 48 hours. The primary end-point was duration of BSA. Secondary endpoints included 30-day mortality, re-hospitalization and length of stay (LOS) from FN. Median values were compared with the Mann–Whitney test. Results Among 229 HSCT patients, 155 (68%) developed FN post-transplant and of those 97 (63%) were without infection (13 EDG and 84 SCG). Initial FN duration of BSA was less in the EDG (3.09 days vs. 4.69 days, P = 0.069). Total antibiotic free days to 30 day follow-up were similar (EDG 24.08 vs SCG 25.19, P = 0.81). Duration of neutropenia was less in the SCG with 7.99 days compared with 11.69 days in the EDG (P = 0.007), but duration of initial fever was less in the EDG (2.55 days vs. 3.33 days, P = 0.023). 30 day mortality was 0% in both groups. Rates of re-hospitalization within 30 days were approximately the same (7.1% vs. 7.6%). LOS from FN was not significantly different with 6.68 days in SCG and 7.75 days in EDG (P = 0.140). More new bacterial infections were identified within 30 days of FN in the SCG than the EDG (10.7% vs. 7.6%). Conclusion Early BSA de-escalation resulted in no significant difference in LOS from FN and fewer days of BSA with 30-day mortality and re-hospitalization rates similar. This data suggest de-escalating BSA prior to ANC recovery is likely safe and leads to less BSA exposure, but more multi-center data are needed. Disclosures All authors: No reported disclosures.

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