Turkish Journal of Hematology Volume: 31 - Issue: 2

More documents

Recommendations

Info

Turk J Hematol 2014;31:111-120 Akan H, et al: Treatment of Invasive Fungal Infections Introduction Invasive fungal infections (IFIs) have emerged as a serious problem affecting morbidity and mortality in the management of patients with hematological malignancies. The continuous introduction of novel approaches and medications in this area influences the clinical behavior of physicians. In order to arrive at a consensus decision, various guidelines have been published and updated. These guidelines make recommendations based on evidence from certain important published articles. However, discordance between clinical research and medical practice comes into question and the implementation of these guidelines or the adaptation of them according to the local regulations of different countries may be troublesome. From this point of view, a critical review of evidence was undertaken by the experts on IFI management in Turkey. We performed a critical appraisal of some studies that have been unconditionally accepted, the results of which have been implemented until today. This paper includes appraisals of 7 key articles on IFI. These articles have been divided into 2 groups according to their subjects. The first group, i.e. the first 3 studies, is generally called the “Walsh studies” [1,2,3] and the efficacies of various antifungal agents used in empirical treatment are compared in these studies. As a standard approach, empirical antifungal treatment is given for the early treatment of fungal infections in neutropenic patients with persistent fever without clinical findings. Although the main aim in these studies is to determine the differences in efficacy of antifungal agents used in empirical treatment, the differences in side effects come to the forefront. The 4 studies in the second group are strategy studies [4,5,6,7]. The use of “prolonged fever/febrile neutropenia” as the sole evidence for fungal infection in empirical treatment has begun to be questioned and the requirement of using diagnostic tools such as high-resolution computed tomography (HRCT) and galactomannan (GM) revealed the probability of the substitution of the empirical approach with new strategies like preemptive treatment or diagnostic-driven treatment. These 4 studies investigate and compare the benefits of empirical versus preemptive approaches as early treatment strategies for IFIs. Outlines of the clinical trials included in this review are found in Table 1. Efficacy Studies In the 3 studies in the first group, Walsh and his colleagues used treatment success as the primary endpoint [1,2,3]. They defined a composite score involving 5 criteria: 7-day survival after the initiation of the studied drug, resolution of fever during the neutropenic period, successful treatment of baseline fungal infection, absence of breakthrough fungal infections while receiving the studied drug or within 7 days after treatment, and no early withdrawal of the studied drug due to toxicity or lack of efficacy. First Study: “Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia” by Walsh et al. [1] Author: Şeniz Öngören Aydın, Associate Professor, MD Previously, 2 randomized placebo-controlled studies on empirical antifungal treatment showed that treatment with conventional amphotericin B deoxycholate decreased the frequency of proven IFIs [8,9]. The newly developed lipid formulations of amphotericin B led to a decrease in doselimiting nephrotoxicity and infusion-related acute toxic effects. Both preclinical and open-label phase 1 and 2 studies demonstrated that liposomal amphotericin B (LAmB) is more efficient and less nephrotoxic than conventional amphotericin B in the treatment of invasive fungal infections (disseminated candidiasis and invasive pulmonary aspergillosis) [10,11,12,13,14,15]. Critical Review of the Study This study comparing empirical LAmB with conventional amphotericin B in neutropenic patients with persistent fever is one of the studies that is cited the most among the papers on antifungal treatment in febrile neutropenic patients. The use of masking is the most important strength of this study. There were 4 important studies that compared LAmB with conventional amphotericin B in the empirical treatment of febrile neutropenic patients [1,16,17,18]. The results of these studies are similar to the results obtained in the Walsh study. The most important contribution of this study in the follow-up and evaluation of febrile neutropenic patients is the defining of the composite score for determining the success of antifungal treatment used. Fever can occur for many reasons other than infection, and treatment success was not based on the sole use of resolution of fever in this study, an aspect of critical importance also acknowledged by the guidelines. Table 1. Number of citations of the articles (31 December 2013). Authors Walsh et al., 1999 [1] 638 Walsh et al., 2002 [2] 517 Walsh et al., 2004 [3] 441 Maertens et al., 2005 [4] 256 Cordonnier et al., 2009 [5] 111 Girmenia et al., 2010 [6] 25 Pagano et al., 2011 [7] 13 Number of citations 112
Akan H, et al: Treatment of Invasive Fungal Infections Turk J Hematol 2014;31:111-120 Regarding statistical significance, the sample size calculated before the study was attained in both groups. However, inclusion and analysis of pediatric and adult patients together (age range: 2-80 years) constitutes one of the weak points of the study. Regarding risk categories, the groups were quite heterogeneous, neutropenia duration was not taken into consideration, patients with allogeneic stem cell transplantation (alloSCT) and autologous stem cell transplantation (ASCT) were classified in the same risk group, and, although there were patients who underwent alloSCT, the duration of neutropenia being short for the development of deep fungal infections was intriguing. Additionally, although the patients who underwent stem cell transplantation were considered as high-risk patients, the total number of patients in the high-risk group was low (i.e. inconsistency in the number of patients with high risk). Although it was mentioned that the groups were comparable regarding antibacterial, antifungal, and antiviral treatment at baseline, the onset of antifungal treatment and time of antibiotic modification/addition (glycopeptides) was not mentioned. Additionally, there is no information on the outcome of patients with candidemia, who were of equal number in both groups at the beginning of the study. Although aggressive interventions (blood culture, bronchoalveolar lavage, percutaneous needle aspiration, and biopsy) were carried out to identify the etiology of fungal infections, most patients were diagnosed to have suspected fungal pneumonia, as in daily practice. The frequency of infusion-related toxicities was lower in patients using LAmB; data showing the results of >7000 infusions support the statistical power of the study. In 2002, Cagnoni reanalyzed the 103 patients who underwent alloSCT who were included in the study of Walsh [19]. Nephrotoxicity (p
Page 1 and 2: Volume 31 Issue 2 June 2014 40 TL I
Page 3 and 4: Contact Information Editorial Corre
Page 5 and 6: TURKISH JOURNAL OF HEMATOLOGY INSTR
Page 7 and 8: Introduction: A brief introduction
Page 9 and 10: e-mail address is very important. E
Page 11 and 12: 188 Primary Adrenal Lymphoma Karima
Page 13: Review Article DOI: 10.4274/tjh.201
Page 17 and 18: Akan H, et al: Treatment of Invasiv
Page 23 and 24: Research Article DOI: 10.4274/tjh.2
Page 25 and 26: Atalay F, et al: sEPCR Levels and T
Page 31 and 32: El-Menshawy N, et al: Clinical Sign
Page 39 and 40: Turk J Hematol 2014;31:136-142 Uz B
Page 47 and 48: Turk J Hematol 2014;31:143-148 Aref
Page 49 and 50: Turk J Hematol 2014;31:143-148 Aref
Page 53 and 54: Sepehrizadeh Z, et al: Cytokine Gen
Page 55 and 56: Sepehrizadeh Z, et al: Cytokine Gen
Page 59 and 60: Atalay A, et al: EBV and PV B19 Aft
Page 61 and 62: Atalay A, et al: EBV and PV B19 Aft
Page 65 and 66:
Mohebbi Far R, et al: Blood Compone
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Tiftik NR, et al: Rho/ROCK and Eryt
Page 73 and 74:
Tiftik NR, et al: Rho/ROCK and Eryt
Page 75 and 76:
Turk J Hematol 2014;31:168-174 Tift
Page 77 and 78:
Case Report DOI: 10.4274/Tjh.2012.0
Page 79 and 80:
Das S, et al: Gelatinous Marrow Tra
Page 81 and 82:
Das S, et al: Gelatinous Marrow Tra
Page 83 and 84:
Özdoğu H, et al: MSCs, Immune Sup
Page 85 and 86:
Özdoğu H, et al: MSCs, Immune Sup
Page 87 and 88:
Kim H, et al: Triple X with ITP Tur
Page 89 and 90:
Kim H, et al: Triple X with ITP Tur
Page 91 and 92:
Kacem K, et al: Primary Adrenal Lym
Page 93 and 94:
Kacem K, et al: Primary Adrenal Lym
Page 95 and 96:
Sargın G, et al: Bone and Bone Mar
Page 97 and 98:
Bilgin UA, et al: Acquired Hemophil
Page 99 and 100:
Letter to the Editor DOI: 10.4274/t
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Images in Hematology DOI: 10.4274/t
Page 113 and 114:
DOI: 10.4274/tjh.2013.0155 2. Morph
Page 115 and 116:
Images in Hematology DOI: 10.4274/T
Page 117:
Clinical Picture in Hematology Turk
show all

Turkish Journal of Hematology Volume: 31 - Issue: 2

Create successful ePaper yourself

Delete template?

Save as template?