scholarly journals Incidence & outcome of invasive fungal infections in patients with febrile neutropenia

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
F S K Hennawy ◽  
M M T Elzimaity ◽  
N N Moustafa ◽  
G M Kamal ◽  
E A Abdelhady ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Primary Diagnosis ◽  
P Value ◽  
Hematopoietic Stem ◽  
Hypertensive Patients ◽  
Lv Mass ◽  
Egyptian Patients ◽  
Lv Diastolic Dysfunction

Abstract Background Invasive fungal infection (IFI) is a major cause morbidity and mortality among patients with hematological malignancies who receive chemotherapy or hematopoietic stem cell transplantation (HSCT). Thus, early diagnosis and treatment of these infections are of crucial importance. Certain factors have been identified as risk factors for IFI. Objectives Assessment of incidence and outcome of IFI in Egyptian patients with febrile neutropenia. Patients and Methods 50 febrile neutropenia episodes were studied. Patients were all subjected to history taking, clinical examination and further investigations including imaging studies, Galactomannan and Mannan antigen assays, and patients were followed up for observing the outcome. Results Our study found that hypertensive patients had significantly reduced LA function as measured by speckle tracking when compared to normotensive controls (P-value < 0.001). Also, many factors were associated with worse LA function in hypertensive patients as old age, high BMI, DM, LV diastolic dysfunction, high LV mass index, larger LA size, lower LA expansion index and higher systolic BP. Conclusion IFI incidence is affected by age, gender, primary diagnosis and severity of neutropenia, and IFI has a worse outcome compared to other causes of febrile neutropenia.

scholarly journals ANTIFUNGAL PROPHYLAXIS IN IMMUNOCOMPROMISED PATIENTS

2016 ◽  
Vol 8 ◽  
pp. e2016040 ◽  
Author(s):  
Lourdes Vazquez
Keyword(s):  
Gold Standard ◽  
Concomitant Medication ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
Risk Of Infection ◽  
Scientific Societies ◽  
Hematopoietic Stem ◽  
Poor Efficacy

Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication.

HLA Match and Mismatch Direction in Cord Blood (CB) Transplantation: Impact On Outcome and Implications for Cord Blood Unit Selection.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2297-2297
Author(s):  
Cladd Stevens ◽  
Carmelita Carrier ◽  
Ludy Dobrila ◽  
Carol Carpenter ◽  
Rodica Ciubotariu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Hematological Malignancies ◽  
Reference Group ◽  
Bone Marrow Failure ◽  
P Value ◽  
Unit Selection ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Relapse Risk

Abstract Abstract 2297 Poster Board II-274 Apparent immunological tolerance allows for transplantation of cord blood (CB) hematopoietic stem cells that are mismatched for human leukocyte antigens (HLA) with the recipient. HLA match, however, affects CB transplant outcome. To explore the possibility that the direction of HLA mismatch (MM) also has an impact on outcomes, we evaluated patients (pts) transplanted in the US with single CB units provided by the New York Blood Center, with 0-2 HLA MM, during the period 1993-2006. We hypothesized that CB grafts with MM in the rejection direction only (pt homozygous at the mismatched locus) would have higher rates of graft failure and, consequently, relatively poor post-transplant survival. Conversely, CB grafts with no rejection MM (i.e., GVHD only MM; CB unit homozygous at the mismatched locus) would have better engraftment and survival. Match level was evaluated at low-intermediate resolution for HLA-A and -B and at high resolution level for -DRB1. Of the 1,207 pts with outcome data (94% of eligible pts), 72% had hematological malignancies, 8% had bone marrow failure and the rest had various genetic diseases. Most pts (92%) had myeloablative conditioning, 26% were ≥16 years of age and 48% had non-Caucasian ancestry. CB grafts were HLA matched in 73 donor/patient pairs. Ninety-eight pairs (8% of total) had only unidirectional MM: 58 in the GVHD direction only (51 with 1 HLA MM; 7 with two) and 40 in the rejection direction only (30 with 1 HLA MM; 10 with two). There were 360 donor/patient pairs with 1 bidirectional MM, 524 with 2 bidirectional MM, 137 with 2 mismatches that were a mixture of bi- and uni-directional, and 5 with both types of unidirectional MM (different loci). In multivariate analyses, compared to CB grafts having 1 bidirectional MM, pts with matched grafts and those with GVHD only MM had faster ANC engraftment (RR=1.7, p=0.037 and RR=1.6, p=0.006, respectively) and improved TRM (RR=0.5, p=0.041 and RR=0.6, p=0.046, respectively), overall mortality (RR=0.6, p=0.041 and RR=0.6, p=0.016, respectively) and disease-free survival (RR=0.6, p=0.055 and RR=0.6, p=0.009, respectively). These grafts had no association with relapse risk in pts with hematological malignancies. In contrast, CB grafts with rejection only MM had a lower engraftment rate (RR=0.7, p=0.086) and a higher relapse rate. These associations were most apparent in patients with hematological malignancies (Table). These relationships were independent of other predictors in the multivariate models and of matching for the donor's non-inherited maternal antigens (NIMA), another factor we have recently found to affect outcome in MM CB transplants. Further, MM direction had no significant association with acute or chronic GVHD. No associations with outcome were found in grafts with a mix of both bi-directional and uni-directional MM or two unidirectional MM. HLA Match and MM Direction in CB Recipients with Hematologic Malignancies Group N 3-year DFS 3-year Relapse RR (95% CI) p value RR (95% CI) p value 0 MM 48 0.4 (0.2 - 0.7) 0.002 0.7 (0.3 - 2.0) 0.499 1-2 MM / GvHD only 35 0.5 (0.3 - 0.9) 0.014 0.6 (0.3 - 1.3) 0.198 1-2 MM / Rejection only 23 1.5 (0.9 - 2.4) 0.136 2.3 (1.2 - 4.6) 0.013 1 Bidirectional MM 249 Reference Group Reference Group 2 Bidirectional MM 415 1.1 (0.9 - 1.4) 0.173 0.8 (0.5 - 1.0) 0.100 2 MM / Mixed Direction 101 1.2 (0.9 - 1.4) 0.240 1.0 (0.6 - 1.6) 0.947 This study demonstrates that direction of HLA MM affects CB transplant outcome. CB units with GVHD only MM had outcomes similar to those of fully matched (6/6) grafts and, according to published reports in children with leukemia, possibly superior to 8/8 allele level bone marrow grafts from unrelated donors. CB units with rejection only MM were associated with poor engraftment and, in pts with hematological malignancies, with increased relapse risk. Assignment of HLA MM direction should be included in CB unit selection algorithms. For pts lacking fully matched grafts, selection of CB units with GVHD only MM will increase the probability of an optimal outcome. Disclosures: No relevant conflicts of interest to declare.

Autopsy Analysis On Epidemiology and Site of Involvement Of Invasive Fungal Infections (IFI) In Hematological Malignancies : A Retrospective Study at Hematologic Tertiary Care  Department

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5589-5589
Author(s):  
Anna Chierichini ◽  
Francesca Monardo ◽  
Barbara Anaclerico ◽  
Paola Anticoli Borza ◽  
Velia Bongarzoni ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Tertiary Care ◽  
Diagnostic Methods ◽  
Diagnostic Tools ◽  
P Value ◽  
Candida Spp ◽  
Acute Leukemias

Abstract Background Clinical diagnosis of IFI is difficult ,due to lack of sensitive and specific diagnostic tools. An assessment of trends concerning the prevalence of IFI is a challenge and postmortem data may be useful to monitor the local epidemiology ,the frequency and the disease patterns. Aim The aim of this retrospective analysis is to determinate the local epidemiology and the prevalence at autopsy of IFI, occurring in hematological malignancies at a single center  over a eleven years period. Methods We have retrospectively reviewed 161 patients – median age  62,5 yrs, range 22 -83 - with hematological malignancies, who underwent autopsy between 2002 -2012. Acute Myeloid Leukemia (AML) were 77, Acute Lymphoid  Leukemia (ALL) 11,  Lymphoproliferative disorders (LPD) 56 and other disorders 17. Acute leukemia pts received systemic antifungal  prophilaxis, whereas the others not absorbable prophilaxis. None patients received transplant procedures. An experienced pathologist evaluated the organ involvement and the IFI pathologic pattern. Fisher’s Exact test was used to recognize the IFI prevalence, the main occurring pathogens and the involved site; a p-value of <0.05 was considered statistically significant. Results The analysis of 161 consecutive autopsies identified 40  pts.(25%)resulting to have IFI; of these, 22 were AML (55%) ,6 ALL (15%),11LPD (28%) and 1 other. Aspergillus  spp. infection was detected in 20 cases (50%), Mucor spp in 8 (20%) and Candida spp. in 12 (30%). Moulds  were prevalent in acute leukemia pts. and Aspergillus spp. is the leading pathogen with respect to Candida and Mucor spp. (p 0,0396),with a statistically significant prevalence in ALL (p 0,0186).The site more involved resulted lung (p 0.0002). Whereas the standardized EORTC/MSG criteria applied in vivo were conclusive for  IFI in 6  pts ( 15%) only, the postmortem findings revealed fungal infections in further 34  pts (85%). Conclusion This analysis confirms that the IFI diagnosis is still an unresolved issue in hematological malignancies. Acute leukemias remain the subset with the higher prevalence of mould infections. As in other largest studies, in our experience Aspergillus spp and lung proved to be the most recurrent pathogen and site of involvement. At now, the diagnostic methods are not still completely able to identify the underlying IFI, thus  the autopsy rate should be increased to achieve a better knowledge of epidemiology and to critically review previous misdiagnosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Community Airborne Mold Spore Counts and Invasive Fungal Disease Risk Among Pediatric Hematological Malignancy and Stem Cell Transplant Patients

2021 ◽  
Author(s):  
Mohammed A Almatrafi ◽  
Victor M Aquino ◽  
Tamra Slone ◽  
Rong Huang ◽  
Michael Sebert
Keyword(s):  
Stem Cell ◽  
Symptom Onset ◽  
Hematological Malignancies ◽  
Hematological Malignancy ◽  
Fungal Infections ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Mold Spore

Abstract Background Patients with hematological malignancies and hematopoietic stem cell transplantation (HSCT) recipients are at risk of developing invasive fungal infections, but the quantitative risk posed by exposure to airborne mold spores in the community has not been well characterized. Methods A single-institution, retrospective cohort study was conducted of pediatric patients treated for hematological malignancies and HSCT recipients between 2014 and 2018. Patients with invasive fungal disease (IFD) due to molds or endemic fungi were identified using published case definitions. Daily airborne mold spore counts were obtained from a local National Allergy Bureau monitoring station and tested for association with IFD cases by zero-inflated Poisson regression. Patients residing outside the region or with symptom onset more than two weeks after admission were excluded from the primary analysis. Results Sixty cases of proven or probable IFD were identified of which 47 cases had symptom onset within 2 weeks of admission and were therefore classified as possible ambulatory onset. The incidence of ambulatory-onset IFD was 1.2 cases per 10,000 patient-days (95% CI, 0.9-1.7). A small excess of ambulatory-onset IFD was seen from July through September during which period spore counts were highest, but this seasonal pattern did not reach statistical significance (P = 0.09). No significant association was found between IFD cases and community mold spore counts over intervals from one to six weeks prior to symptom onset. Conclusions There was no significant association between IFD cases and community airborne mold spore counts among pediatric hematological malignancy and HSCT patients in this region.

The Role of PET-CT for the Diagnosis of Infections in Hemato-Oncological Patients with Persistent Febrile Neutropenia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4289-4289
Author(s):  
Anat Gafter-Gvili ◽  
Mical Paul ◽  
Hanna Bernstine ◽  
Liat Vidal ◽  
Ron Ram ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Primary Analysis ◽  
Abdominal Ct ◽  
Pet Ct ◽  
Total Body

Abstract Abstract 4289 Background and aims: Patients with hematological malignancies and prolonged febrile neutropenia are at high risk for bacterial and invasive fungal infections (IFIs). We aimed to evaluate the role of PET-CT for detection of such infections among these patients. Methods: Prospective cohort study of patients with hematological malignancies given intensive conventional chemotherapy and hematopoietic-cell transplantation (HCT) at our center. All consecutive, consenting patients with neutropenia (<500/mm3) and persistent or breakthrough fever despite broad spectrum antibiotics (>5days) had a PET-CT examination. The CT component of the PET-CT was a contrast-enhanced diagnostic CT. Results were available to clinicians in real time. Blinded evaluation of chest and sinus CT and the full PET-CT scan (i.e.chest, sinus CT, abdominal CT, and FDG uptake) were compared with the final clinical diagnosis 30 days after neutropenia resolution, as determined by an expert panel consisting of a hematologist and an infectious diseases expert. Patients were included more than once in the study for different episodes of persistent febrile neutropenia and each episode could receive more than one diagnosis at 30 days. Episodes concluding in no documented infection or other pathological process were classified as fever of unknown origin (FUO). Results: Between January 2008 and January 2011, 91 PET-CT examinations were performed in 79 patients. Median age was 56 (range: 21–85) years. PET-CT was performed after a median of 10 days from last chemotherapy (range: 0–255). Patients were neutropenic for a median of 11 (range:1–100) days. Most patients had acute leukemia (71 episodes), 7 patients underwent allogeneic HCT and 6 patients with lymphoma underwent autologous HCT. The types and number of individual diagnoses are listed in the table. Of the 91 PET-CT examinations, 23 episodes had two or more diagnoses, most commonly a combination of bacterial and fungal infection. Of 28 microbiologically documented infections (MDIs), bacteremia was the diagnosis in 20 episodes, most commonly without a focal source. In the primary analysis we considered FUO as “no disease” and all else as “disease”. The sensitivity to detect any infection or non-infectious pathology in chest/sinus CT, was 58.8% (60 /102 diagnoses). The respective sensitivity for PET- CT was 85.3% (87/102). The difference in sensitivity was 26.5% (95% confidence interval 21.4% to 31.6%), matched sample p<0.001. The specificities of CT and PET-CT were not significantly different, 66.7% (10/15 episodes of FUO) and 60% (9/15), respectively. Of note, all 7 proven or probable fungal infections were FDG- positive. In 28 cases, PET-CT demonstrated findings which were not detected on chest/sinus CT (27.5% of diagnoses).These were mainly abdominal infections (as appendicitis, diverticulitis, etc.) and abscesses (perianal, splenic, etc.). When we compared PET-CT to total body (chest, sinus and abdominal) CT, we found that 7 of these cases were found only on PETCT. The sensitivity of total body CT to detect disease was 78.4% (80/102). PET-CT resulted in modifications of patients’ management in 46 (55%) cases. These included change in antibiotics (14 cases), change in antifungals (14), change in both (5), an invasive diagnostic procedure (7), a surgical procedure (appendectomy, 3) and abscess drainage (4). Conclusions: PET-CT has a higher sensitivity with no loss of specificity compared to chest/sinus CT in patients with persistent febrile neutropenia. The increase in sensitivity afforded by PET-CT was mainly due to the addition of abdominal CT. Thus, PET-CT has a potential role for the diagnosis of infections in neutropenic patients with persistent fever. Disclosures: No relevant conflicts of interest to declare.

Prevention of Graft-Versus-Host Disease (GVHD) with Tacrolimus after Allogeneic Grafting for Hematological Malignancies Following Sub-Myeloablative Conditioning.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5321-5321
Author(s):  
Joseph Fay ◽  
Giovanna Saracino ◽  
Edward Agura ◽  
Brian Berryman ◽  
Luis Pineiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Post Transplant

Abstract Severe acute or chronic GVHD following allogeneic hematopoietic stem cell transplantation therapy (HSCT) has a deleterious effect on the successful treatment of hematological malignancies. We have retrospectively studied mycophenolate mofetil (MMF) and tacrolimus (FK) or cyclosporine (CSA) following allogeneic HCST in the prevention of GVDH and the induction of immune tolerance in 93 patients with hematological malignancies using non-myeolablative pre-transplant conditioning. In the current study, there were 35 patients with leukemia, 36 patients with lymphoma, 12 patients with myelodysplastic syndrome or a myeloproliferative disorder and 10 patients with multiple myeloma. There were 63 women and the median age was 42 (15–75) years. Twenty patients had relapsed after previous autologous or allogeneic HSCT and 45 patients were older than 59 years. The remaining patients had co-morbid medical conditions that precluded the use of chemotherapy/radiotherapy dose-intensive pre-conditioning. Conditioning prior to allogeneic HSCT (94 blood stem cell grafts and 1 marrow graft) was fludarabine (90 mg/m2 in three daily doses) and TBI (200cGy) in 86 patients, fludarabine (120 mg/m2 in 4 daily doses) and cyclophosphamide (50mg/kg) in 5 patients, and TBI (200 cGy) only in 4 patients. Forty-three patients received sibling and 50 unrelated grafts. Median follow-up post transplant is 3.0 (0.2–6.1) years. Five (5.3%) patients did not experience sustained hematological chimerism post-transplant. MMF and FK were administered to 33 recipients and MMF and CSA to 60 recipients. The dose and schedule of MMF, CSA and FK have been published (Laport et al. Blood, 2006 and Fay et al. Blood, 1996.) There was no difference in the degree of HLA mismatching between the two groups of patients. Cumulative incidences were used to estimate the incidence of acute and chronic GVHD, all deaths and disease progressions not related to GVHD being considered as the competing events. The Gray test was used to compare cumulative incidences between groups. The unadjusted cumulative incidence of grade III–IV acute GVHD that required oral or systemic corticosteroid therapy, was 54% (95% CI, 40%–68%) in evaluable patients who received CSA in contrast to 38% (95% CI, 18%–58%) in patients who received FK (p-value=0.25). Furthermore, the unadjusted cumulative incidence of extensive chronic GVHD at 1 year was 45% (95% CI, 32%–58%) for CSA versus 34% (95% CI, 14%–54%) for FK (p-value=0.48). Progression-free survival between patients who received FK or CSA at the time of the analysis of this study is similar (p-value=0.6191). The progression-free survival at 1 year was 43% (95% confidence interval [CI], 24%–62%) for CSA versus 43% (95% CI, 31%–55%) for FK. Analyses of the overall morbidity and the incidence of infectious complications between the 2 groups are ongoing. FK combined with MMF may be superior to CSA and MMF in the prevention of GVHD post sub-myeloablative allogeneic HSCT therapy for hematological malignancies and FK may result in improvement of treatment outcome. We believe further study is warranted.

Optimal Use of Granulocyte Colony Stimulating Factor (G-CSF) after Autologous Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2519-2519
Author(s):  
Firas Al Sabty ◽  
Martin Mistrik ◽  
Mikuláš Hrubiško ◽  
Eva Bojtárová ◽  
Ján Martinka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Febrile Neutropenia ◽  
Stem Cell Transplantation ◽  
Fungal Infection ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Fungal Infections ◽  
Hematopoietic Stem ◽  
Lymphoid Malignancies

Abstract Introduction:high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT) is widely used in the treatment of patients with haematological and non-haematological malignancies. One of the most common causes of mortality after HSCT is infection during the time of prolonged neutropenia. Prolonged neutropenia more than 7 days increase the risk of fungal infections and it is an indication for the use of antifungal prophylaxis. After hematopoietic SCT, G-CSF is commonly used to enhance stem cell engraftment to minimize the morbidity and mortality associated with prolonged neutropenia. However, there is no consensus on the optimal use of G-CSF after autoHSCT, most studies have been conducted on small numbers of patients and have varied significantly in patient’s demographics, G-CSF dosage regimen and other factors affecting outcomes. Objective:restrospective study to evaluate the efficacy of early vs. delayed initiation of G-CSF after autoHSCT in patients with lymphoid malignancies. Methods: between January 2009 and July 2014, 117 patients with lymphoid malignancies who underwent autoHSCT in the Department of Hematology and Transfusion medicine in Bratislava were included. The patients were divided into two groups; in the first group (43 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied late (on day 6.-8.) after autoHSCT. In the second group (74 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied early (on day 3.-4.) after autoHSCT. All patients received standard conditioning regimen for the underlying disease, and standard supportive treatment, including treatment of febrile neutropenia. Patient’s demographics are shown in table 1. Statistical analysis was performed using SPSS statistical software v. 20, with significant Pvalue of 0.05 (two-tailed). Results: sever neutropenia (ANC < 0.5 x 109) and very severe neutropenia (ANC < 0.1 x 109) for more than 7 days were recorded as following: in the first group (delayed G-CSF), 34/42 (81%) and 25/41 (61%) patients respectively. In the second group (early G-CSF), 11/66 (17%) and 2/52 (4%) patients respectively (RR = 4.8, 95% CI = 2.7 to 8.4 and RR = 15, 95% CI = 3.9 to 63). Median time to engraftment of leukocytes above 1, granulocytes above 0.5, and 0.1 x 109/l was 6, 5, and 4 days for patients who received G-CSF early and 7, 7 and 5 days for patients who received G-CSF late (P <0001). The median duration of hospitalization was 19 (15-28) days in the first group and 16 (11-23) days in the second group (P = 0.001, 95% CI =2.02-4.17). There was no significant difference in the rate of febrile neutropenia in both groups (P = 0.53), but the rate of fungal infection and the use of HRCT scan of the lung was higher in the group of patients who received delayed G-CSF than early G-CSF (19% vs. 3%, P=0.005) and (23% vs. 6%, P=0.007) respectively. Conclusion:early application of G-CSF (3rd-4th day) after autologous HSCT accelerates engraftment, shorten the duration of neutropenia, reduce the risk of infectious complications (especially fungal infections), reduce the use of antimicrobial drugs, shorten the hospital stay and overall costs. Table.1 Delayed application of G-CSF Early application of G-CSF Patient N. 43 74 Age, m edian(range) 60 (39-67) years 59 (33-68) years P = 0.694 Sex P = 0.079 Male, N (%) 16 (37%) 40 (54%) Female, N (%) 27 (63%) 34 (46%) CD34+cells x106/kg, m edian(range) 2.5 (1.3-5.6) 2.3 (1.3-4.5) P = 0.138 Diagnosis P = 0.855 Multiple myeloma, N (%) 41 (95%) 72 (97%) NHL, N (%) 2 (5%) 2 (3%) ECOG performance status P = 0.221 0 35 (82%) 53 (72%) 1 7 (16%) 18 (24%) 2 1 (2%) 2 (3%) 3 0 0 4 0 1 (1%) Engraftment , median(range) Leu. > 1 x 109/l 7 (4-12) days 6 (3-9) days P ≤ 0,0001 Neut.> 0.5 x 109/l 7 (5-9) days 5 (3-7) days P ≤ 0,0001 Neut. > 0.1 x 109/l 5 (3-6) days 4 (2-6) days P ≤ 0,0001 Hospitalization, median(range) 19 (15-28) days 16 (11-23) days P= 0,001 Sever neutropenia ≥ 7 days, N (%) 34/42 (81%) 11/66 (17%) RR = 4.8, 95% CI = 2.7 to 8.4 Very sever neutropenia ≥ 7 days, N (%) 25/41 (61%) 2/52(4%) RR = 15, 95% CI = 3.9 to 63 Febrile neutropenia, N (%) 40 (93%) 64 (88%) P = 0.531 Invasive fungal infection, N (%) 8/43 (19%) 2/73 (3%) P = 0,005 HRCT scan use, N (%) 10 (23%) 4 (6%) P = 0.007 Cost 3582 (787-18187) Eur. 1408 (263-2143) Eur. P=0,041 Disclosures No relevant conflicts of interest to declare.

D-Index–Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority Trial

2020 ◽  
Vol 38 (8) ◽  
pp. 815-822 ◽  
Author(s):  
Yoshinobu Kanda ◽  
Shun-ichi Kimura ◽  
Masaki Iino ◽  
Takahiro Fukuda ◽  
Emiko Sakaida ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Fungal Infection ◽  
Antifungal Therapy ◽  
Invasive Fungal Infection ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Controlled Trial ◽  
Horizontal Line ◽  
Hematopoietic Stem ◽  
Randomized Controlled

PURPOSE Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients, it is associated with overtreatment. The D-index, calculated as the area surrounded by the neutrophil curve and the horizontal line at a neutrophil count of 500/μL, reflects both the duration and depth of neutropenia and enables real-time monitoring of the risk of invasive fungal infection in individual patients at no cost. We investigated a novel approach for patients with persistent FN called D-index–guided early antifungal therapy (DET), in which antifungal treatment is postponed until a D-index reaches 5,500 or the detection of positive serum or imaging tests, and compared it with EAT in this multicenter open-label noninferiority randomized controlled trial. PATIENTS AND METHODS We randomly assigned 423 patients who underwent chemotherapy or hematopoietic stem-cell transplantation for hematologic malignancies to the EAT or DET group. The prophylactic use of antifungal agents other than polyenes, echinocandins, or voriconazole was allowed. Micafungin at 150 mg per day was administered as EAT or DET. RESULTS In an intent-to-treat analysis of 413 patients, the incidence of probable/proven invasive fungal infection was 2.5% in the EAT group and 0.5% in the DET group, which fulfilled the predetermined criterion of noninferiority of the DET group (−2.0%; 90% CI, −4.0% to 0.1%). The survival rate was 98.0% versus 98.6% at day 42 and 96.4% versus 96.2% at day 84. The use of micafungin was significantly reduced in the DET group (60.2% v 32.5%; P < .001). CONCLUSION A novel strategy, DET, decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy.

Thymic Shielding (TS) in Recipients of Total Body Irradiation (TBI) and Alternative Donor Hematopoietic Stem Cell Transplant (AD-HSCT): Reduced Risk of Opportunistic Infection in Patients with Fanconi Anemia (FA).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3134-3134 ◽  
Author(s):  
Margaret L. MacMillan ◽  
Bruce R. Blazar ◽  
Todd E. DeFor ◽  
Kathryn Dusenbery ◽  
John E. Wagner
Keyword(s):  
Stem Cell ◽  
Opportunistic Infection ◽  
Lower Risk ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
P Value ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Preparative Regimen

Abstract Delayed immune reconstitution and consequent opportunistic infections remain major obstacles to the successful application of HSCT, particularly in older patients, those with HLA mismatched donors and in selected diseases, such as FA. Based on preclinical work suggesting that TS may improve immune reconstitution in recipients of TBI and allogeneic HSCT (J Immunol1987:139:358), we evaluated the safety and potential efficacy of TS in FA patients. After CT localization of the thymus, 5HVL cerrubend blocks were fabricated and used to shield the thymus from both the anterior and posterior TBI fields. Thymus blocks were attached to special TBI stand brackets that secure the lung compensators. Otherwise all patients received the standard preparative regimen consisting of fludarabine 175 mg/m2, cyclosphosphamide 40 mg/kg, single fraction TBI 450 cGy, and antithymocyte globulin, with cyclosporine and short course methylprednisolone as GVHD immunoprophylaxis. In order to assess the potential risks and benefits of TS, we compared transplant outcomes of these FA patients who received TS to FA patients treated with the exact same preparative regimen without TS. Between April 1999–June 2006, 59 FA patients underwent AD-HSCT at the University of Minnesota; 16 patients had TBI with TS and 43 had TBI without TS. For those with and without TS, donors were HLA matched (n=42) or mismatched (n=17), and stem cell sources were T cell depleted bone marrow (n=9 vs n=38) or umbilical cord blood (n=7 vs n=5). While excess graft failure was considered to be the principal toxicity risk in recipients of TS, incidence of engraftment was similar in those with and without TS (94% vs 97% respectively, p=.46). Although not statistically significant, survival at one year was higher in FA patients with TS (67% vs 53% respectively, p=.46). However, as shown, TS was associated with a significantly lower risk of all three categories of opportunistic infection after HSCT (Table 1). Table 1: Impact of TS on HSCT Outcomes Preparative Regimen Probability of Neutrophil Engraftment (95% CI) Probability of Survival at 1 Year (95% CI) Total # Infections # Bacterial Infections # Viral Infections # Fungal Infections TBI with TS (n=16 patients) 94 (82–100) 67 (23–91) 9 4 3 2 TBI Without TS (n=43 patients) 97 (92–100) 53 (38–68) 126 68 37 21 P value NS NS <.01 <.01 <.01 <.01 In conclusion, TS in recipients of TBI is associated with significantly lower risk of opportunistic infections without any deleterious effect on hematopoietic recovery in recipients of AD-HSCT. While these results indicate that TS reduces the infection rate and potentially improves survival in patients with FA, they also suggests that TS should be considered for other high risk populations (e.g. adults) and in those with other non malignant disorders. While it appears that immune reconstitution is improved based on the reduced incidence of opportunistic infections, correlative laboratory assessments (TREC, CD4 recovery) are currently being performed.

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