Secondary Antifungal Prophylaxis Research Articles

Secondary antifungal prophylaxis in hematological malignancy patients with previous invasive fungal disease

Invasive fungal disease (IFD) causes a high morbidity and mortality in patients with hematological malignancies. Reactivation of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is very common and associated with poor prognosis. Secondary antifungal prophylaxis (SAP) is effective in preventing IFD recurrence. With effective SAP, a history of IFD is not an absolute contraindication to allogeneic HSCT or continuation of high-dose chemotherapy. In recent years, a variety of antifungal drugs such as voriconazole, itraconazole, AmB and caspofungin have been found to be effective for SAP. However, its management during granulocytopenia and immunosuppression remains challenging. This review summarizes the current status of SAP in patients with hematological malignancies.

Secondary antifungal prophylaxis in pediatric hematopoietic stem cell transplants.

Invasive fungal infections (IFIs) constitute a leading cause of morbidity and infection-related mortality among hematopoietic stem cell transplant (HSCT) recipients. With the use of secondary prophylaxis, a history of IFI is not an absolute contraindication to allo-HSCT. However, still, IFI recurrence remains a risk factor for transplant-related mortality. In this study, of the 105 children undergoing HSCT between April 2010 and February 2013, 10 patients who had IFI history before transplantation and had undergone allo-HSCT were evaluated retrospectively to investigate results of secondary prophylaxis. In conclusion, our study shows that amphotericin B and caspofungin was successful as secondary antifungal prophylaxis agents with no relapse of IFI. In addition, after engraftment, secondary prophylaxis was continued with voriconazole orally in 4 patients that yielded good results.

Secondary antifungal prophylaxis in hematological malignancy patients with previous invasive fungal disease: a retrospective analysis.

BackgroundInvasive fungal disease (IFD) causes morbidity and mortality in patients with hematological malignancy. Recurrence of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is associated with poor prognosis. The present study aimed to investigate the efficacy of different strategies of secondary antifungal prophylaxis (SAP) for IFD and choose an appropriate SAP regimen.MethodsClinical data of patients with previous IFD who underwent chemotherapy or HSCT between Jan 2008 and Jun 2013 were retrospectively reviewed and followed up to 180 days post-chemotherapy or HSCT. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. The efficacy of different strategies for SAP and risk factors influencing the failure of SAP were evaluated.ResultsOf the 164 patients enrolled, 121 patients received SAP regimen (73.78%), and IFD recurred in 40 patients: 16.5% (20/121) in SAP group and 46.5% (20/43) in non-SAP group. In SAP group, 58 received SAP agents which were proven effective for their previous IFD, while other 63 patients received other broad-spectrum antifungal agents. There was no significant difference in the recurrence rates between these two subgroups (13.8% (8/58) vs 19.0% (12/63), P = 0.437). The IFD recurrence rates were statistically significant between patients with allogeneic HSCT and chemotherapy or autologous HSCT (25% vs 8.2%, P = 0.013). Multivariate analysis indicated that allogeneic HSCT was the independent risk factor of IFD recurrence after SAP.ConclusionsSecondary antifungal prophylaxis is necessary to prevent IFD recurrence in patients with hematological malignancy, especially for patients in the setting of allogeneic HSCT.

Role of Surgical Resection in Allogeneic Hematopoietic Stem Cell Transplant Recipients with Prior Pulmonary Aspergillosis

▪Backgroud: Invasive fungal disease (IFD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with a history of invasive pulmonary aspergillosis (IPA), especially those with residual pulmonary lesions at transplantation, are at high risk for IFD relapse after allo-HSCT. Since antifungal chemotherapy might be unable to eradicate IPA, surgical resection of pulmonary lesions is suggested to decrease the risk of IPA relapse. In this study, we retrospectively analyzed the outcome of patients who had persistent pulmonary cavity lesions or nodule after initial antifungal treatment.Methods: Between January 2007 and June 2014, a total of 129 patients with a history of IPA underwent allo-HSCT at Nanfang Hospital. Fourteen of these patients had persistent cavity lesions or nodule with more than 2cm in diameter in lung (cavity lesion in 10 and nodule in 4) after initial antifungal treatment (>1 month). Eight of the 14 patients underwent thoracescopic surgery before transplantation including 6 receiving wedge resections and 2 receiving lobectomies. The other 6 patients did not have surgery because of primary underlying diseases (non-complete remission) or multiple sites of lesions. The median duration of initial antifungal treatment pre-transplants were 179 days (range, 92-338 days) and 117.5 days (range, 60-132 days) in the patients with and without surgery, respectively. All the patients were given secondary antifungal prophylaxis (SAP) from the start of the conditioning until 90 days post-transplantation or until eradication of residual lesions. The SAP agents were chosen based on treatment response to initial antifungal therapy.Results: Of the 8 patients undergoing surgery, the underlying primary diseases included acute lymphoblastic leukemia in 5 and acute myelogenous leukemia in 3. The median time from diagnosis of IPA to surgery was 169.5 days (range, 73-330 days). Seven patients received related donor and 1 received unrelated donor transplantation. HLA-matched transplantation was conducted in 6 patients and HLA-mismatched transplantation was conducted in 2. Three patients received standard conditioning and 5 received intensified conditioning. In the 6 patients without surgery, the underlying primary diseases were acute myelogenous leukemia in 3, acute lymphoblastic leukemia in 2 and acute biphenotypic leukemia in 1. Five of these 6 patients underwent related donor transplantation and 1 underwent unrelated donor transplantation; HLA-matched transplants was conducted in 5 patients and HLA-mismatched transplants was conducted in 1. Standard conditioning were given in 3/6 patients and intensified conditioning in 3/6. After transplantation, none of the 8 patients with surgery experienced IFD relapse while 3 of the 6 patients without surgery experienced IFD progressing including 1 died of hemoptysis caused by IPA. The median duration of SAP after HSCT were 96 days (range, 73-119 days) in patients with surgery and 116.5 days (range, 101-183 days) in patients without surgery. The patients with surgery seemed to have the trend of low incidence of IPA relapse than those without surgery after allo-HSCT (P=0.055). Besides, the incidences f IPA relapse were comparative among the patients with surgery and those who achieved complete remission of IPA at transplantation (P=0.595).Conclusions: For patients with persistent cavity or nodules in lung, surgical resection followed by SAP might be effective to decrease the risk of IPA relapse after transplantation. DisclosuresLiu:National Natural Science Foundation of China (81270647, 81300445, 81200388): Research Funding; National High Technology Research and Development Program of China (863 Program) (2011AA020105): Research Funding; National Public Health Grand Research Foundation (201202017): Research Funding; Natural Science Foundation of Guangdong Province (S2012010009299): Research Funding; the project of health collaborative innovation of Guangzhou city (201400000003-4, 201400000003-1): Research Funding; the Technology Plan of Guangdong Province of China (2012B031800403): Research Funding; the project of the Zhujiang Science & Technology Star of Guangzhou city (2013027): Research Funding.

Antifungal Agents for Secondary Prophylaxis Based on Response to Initial Antifungal Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients with Prior Pulmonary Aspergillosis

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation.

Primary or secondary antifungal prophylaxis in patients with hematological maligancies: efficacy and damage.

BackgroundPatients with hematological malignancies often develop febrile neutropenia (FN) as a complication of cancer chemotherapy. Primary or secondary antifungal prophylaxis is recommended for patients with hematological malignancies to reduce the risk of invasive fungal infection (IFI). This study retrospectively evaluated the efficacy and potential harm of administration of primary and secondary antifungal prophylaxis to patients with hematological malignancies at one hospital.MethodsAll patients with hematological malignancies older than 14 years of age who had experienced at least one FN attack during chemotherapy while being treated at one hospital between November 2010 and November 2012 were retrospectively evaluated.ResultsA total of 282 FN episodes in 126 consecutive patients were examined during a 2-year study period. The mean patient age was 51.73±14.4 years (range: 17–82 years), and 66 patients were male. Primary prophylaxis with posaconazole was administered to 13 patients and systemic antifungal treatment under induction or consolidation chemotherapy to seven patients. Of 26 patients who received secondary antifungal prophylaxis with either oral voriconazole (n=17) or posaconazole (n=6) during 46 FN episodes, systemic antifungal therapy was administered in 16 of 38 episodes and three of eight episodes, respectively. Secondary antifungal prophylaxis with caspofungin was found effective in treating six FN episodes in three patients who had experienced at least two persistent candidemia attacks. The mortality rates associated with IFI were 9% in the first year, 2% in the second year, and 6% overall. The mortality rates associated with candidemia were 33% in the first year, 22% in the second year, and 27% overall.ConclusionPrimary antifungal prophylaxis should be administered to selected patients on the basis of consideration of efficacy, cost, and potential harm. Use of secondary prophylaxis may reduce systemic antifungal use and IFI frequency but may increase risk of colonization and infection with azole-resistant fungal strains.

Standards in prophylaxis: Prevention of invasive aspergillosis in patients with hematologic malignancies

Best practice strategies regarding primary antifungal prophylaxis in leukemia patients and in hematopoietic stem cell transplant recipients continue to evolve. For this prophylaxis to be beneficial and cost-effective, the risk of a life-threatening invasive fungal infection (IFI) should outweigh the risks of toxic effects and drug interactions introduced by the antifungal agent used. Furthermore, the improved survival of such patients with IFIs creates pressing issues regarding optimization of secondary antifungal prophylaxis. Not all patients with hematologic cancer recipients have the same risk of IFIs. Well tolerated and pharmacokinetically reliable, broad-spectrum antifungals, especially azoles, have the potential for reducing IFI-associated mortality in these patients. Further refinement of risk stratification and risk/benefit analysis (including pharmacoeconomic analysis) is needed. Stratification of IFI risk could be further sharpened based on emerging genetic, metabolic risk factors. Despite robust data from randomized prospective studies, personalized decisions and reliance on institution-specific epidemiologic data are still expected to be a major part of “art and science” of prophylaxis for fungal infections in severely immunosuppressed hosts.

Cross-sectional investigation of first-choice of antifungal agents in empirical and preemptive antifungal therapy for patients with hematological malignancies

To describe the constituent ratio of different kinds of antifungal agents as first choice in empirical or preemptive antifungal therapy for patients with hematological malignancies received chemotherapy or hematopoietic stem cell transplantation (HSCT). Between 2008 January and 2009 December, 367 patients received chemotherapy or HSCT from 15 medical centers in China were collected. The strategies of antifungal therapy and the first-choice antifungal agents were analyzed. Of them, 282(76.8%) patients received empirical antifungal therapy, 85(23.2%) preemptive therapy. The number of first choice antifungal agents were 55(15.0%) of fluconazole, 174(47.4%) of itraconazole, 39(10.6%) of voriconazole, 57(15.5%) of traditional/lipid formulation amphotericin B, 26(7.1%) of caspofungin, 7(1.9%) of micafungin, and 9(2.5%) of combination antifungal therapy respectively. Moreover, voriconazole and combination antifungal agents were more often selected for preemptive antifungal therapy, while the probabilities of itraconazole were the highest in both empirical and preemptive strategies. More patients undergoing HSCT were first given itraconazole or caspofungin for antifungal therapy, while amphotericin B, fluconazole and voriconazole were more administered in patients received chemotherapy. Caspofungin and combined antifungal agents were more often used for patients with secondary antifungal prophylaxis, while itraconazole was usually used for patients with no prophylaxis or primary antifungal prophylaxis. Empirical antifungal therapy was more administered in hematological malignancies patients received chemotherapy or HSCT. Itraconazole was the most commonly used agent for antifungal therapy followed by amphotericin, fluconazole, voriconazole and echinocandin agents.

Itraconazole for secondary prophylaxis of invasive fungal infection in patients undergoing chemotherapy and stem cell transplantation

To evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state. A phase IV prospective, open-label, multicenter trial was conducted to evaluate itraconazole (200 mg q12h intravenously d1-2, 200 mg/d) as secondary antifungal prophylaxis in patients (18-65 years old) undergoing chemotherapy or HSCT with previous proven or probable IFI. Itraconazole was started when patients' neutrophils＜1.5 × 10⁹/L, and stopped when chemotherapy patients' neutrophils ＞0.5 × 10⁹/L and stem cell transplant recipients' neutrophils＞1.0 × 10⁹/L. The primary end-point of the study was the incidence of proven, probable or possible IFI. Seventy one patients from November 2008 to September 2010 were enrolled in the trial. The median duration of itraconazole prophylaxis was 14 (4-35) days. No patients died of drug-related toxicity within trial. Five cases occurred IFI during the trial. The cumulative incidence of invasive fungal disease was 7.0%. One patient was withdrawn from the study due to treatment-related adverse events (liver malfunction and severe phlebitis). Itraconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after chemotherapy and allogeneic HSCT. The observed incidence of 7.0% is considerably lower than the relapse rate reported in historical controls, suggesting that itraconazole is a promising prophylactic agent in this population.

Risk factors for recurrence of invasive fungal infection during secondary antifungal prophylaxis in allogeneic hematopoietic stem cell transplant recipients

Invasive fungal infections (IFIs) are a major cause of mortality among allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Thanks to the widespread use of secondary antifungal prophylaxis (SAP), a history of IFI is not an absolute contraindication to allo-HSCT. However, IFI recurrence remains a risk factor for transplant-related mortality. To evaluate the risk factors for IFI recurrence in allo-HSCT patients receiving SAP, we performed a retrospective analysis of 90 individuals treated at our hospital. SAP antifungal agents included fluconazole (n=28), voriconazole (n=25), itraconazole (n=23), caspofungin (n=7), and micafungin (n=7). By day +100, recurrent IFI had occurred in 23 (25.5%) patients. Our multivariate analysis identified 4 factors significantly associated with a risk of IFI recurrence within 100days of allo-HSCT: duration of neutropenia >18days, presence of severe acute graft-versus-host disease (aGVHD), <70-day interval between previous infection and transplantation, and use of a narrow-spectrum SAP agent (P=0.008, 0.010, 0.041, and 0.001, respectively). Of the 87 patients who remained in the study for the duration of the follow-up period (median length: 551days), 26 (29.9%) died; only 7 (8.0%) of these deaths resulted from a severe fungal infection. These results suggest that transplantation outcome can be improved by adequate antifungal treatment before transplantation, better prevention of, and therapy for, severe aGVHD, use of granulocyte colony-stimulating factor to reduce the duration of neutropenia, and use of broad-spectrum prophylaxis agents.

Fungal pathogens and primary antifungal prophylaxis in patients with hematological malignancies: one year experience.

Febrile neutropenia (FN) is generally a complication of cancer chemotherapy in patients with hematological malignancies. To evaluate the febrile neutropenia episodes of hematological patients and their outcomes with respect to fungal pathogens, primary antifungal prophylaxis antifungal therapy. All consecutive patients older than 14 years of age and who developed febrile neutropenia episodes from September 2010 to November 2011 were incorporated into this study. In total, we retrospectively evaluated 86 consecutive patients and their 148 neutropenic episodes. Of the 86 patients, 45 were male and the mean age was 47,65±15,06 years (range: 17-82 years). The mean MASCC score was 18,72 ± 9,43. Systemic antifungal drug was initiated to 17 patients with probable fungal infection and 12 patients with possible fungal infection. Of seven patients who received posaconazole prophylaxis, five were treated with systemic fungal infection due to possible fungal infection. It is obvious that more studies focused on primary prophylaxis are needed and primary or secondary antifungal prophylaxis should be evaluated in terms of provided benefits and disadvantages. Timely and appropriately initiated antifungal treatment is one of the most important factors for a good prognosis for recovery from a neutropenic phase.

Primary and Secondary Antifungal Prophylaxis in the Immunocompromised Child: Where do we Stand?

Invasive opportunistic fungal infections are important causes of morbidity and mortality in immunocompromised children undergoing chemotherapy or haematopoietic stem cell transplantation (HSCT). Primary and secondary chemoprophylaxis of invasive fungal infections targets high risk disease-related patients with acute myeloid leukaemia, high risk acute lymphoblastic leukaemias, recurrent leukaemias and those following allogeneic HSCT. The rationale for antifungal prophylaxis in high risk patients comes from two different aspects. On the one hand, is the difficulty of instant diagnosis and, on the other hand, the consequences of morbidity and mortality by invasive infectious diseases. Although we have limited pediatric data concerning antifungal prophylaxis, it has become part of infectious disease supportive care schemes in most of paediatric leukaemia and HSCT centres. This review has insights on the evidence concerning primary and secondary antifungal prophylaxis in immunocompromised children. Although our knowledge comes from large adult studies concerning antifungal agents, there is a great need for evidence of primary or secondary antifungal prophylaxis in large pediatric clinical trials in order to have a consensus in primary and secondary antifungal prophylaxis in immunocompromised children.

Secondary Antifungal Prophylaxis in Allogeneic Hematopoietic Stem Cell Recipients

Abstract 4140 BackgroundInvasive fungal infection (IFI) is a serious complication in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is widely accepted that the patients with stable fungal infection is not a contraindication for allo-HSCT, but whether transplantation can be done in the patients with active fungal infections is still a matter of discussion. In addition, the optimal agent for SAP is not well defined. In this study, we investigated the efficacy of SPA for recipients in stable state or active state of prior invasive pulmonary aspergillosis (IPA). The choice of prophylaxis agent was based on treatment response of initial antifungal therapy. MethodsA total of 63 patients with prior IPA undergoing allo-HSCT were enrolled in this prospective study. Forty-one patients with IPA were in stable and 22 patients were in active state at the time of transplant. SAP was given from the start of the conditioning until 90 days after transplantation for patients in stable state or until eradication of residual foci for patients in active state. The same agent was given for SAP if patients developed acute GVHD and treated with corticosteroids. The agents of SAP included Itraconazole in 16, Vorinazole in 30, Caspofungin in 12 and Amphotericin B in 5 cases. In addition, surgery was performed in 3 patients who had the cavity lesion of more than 2cm diameter in lung before HSCT. ResultsThe median time of SAP was 96 days (range, 13 to 183). None of the patients was interrupted prophylaxis due to event of intolerance. At a median follow-up period of 260 days (range, 13–2010), 22 patients (34.9%) occurred the relapse of IPA, including 11 (17.5%) occurred SAP failure. Two-year cumulative incidence of IPA relapse was 42.8%±7.3%. The incidence of SAP failure was similar between the patients with active IPA and stable IPA (26.9% vs. 12.4%; P=0.174). The rates of SAP failure were not different between the different antifungal agents. Multivariate analyses showed II to IV aGVHD was the risk factor of SAP failure (RR= 14.4, 95%CI 3.011–68.864, P=0.001). None of the 3 patients underwent surgery occurred IPA relapse. And 3 patients with the cavity lesion of more than 2cm diameter in lung not received surgery all occurred IPA after HSCT including one died of hemoptysis. All the patients occurred IPA relapse received the salvage therapy for IFI. Seven patients achieved CR, 11 achieved PR and 4 patients had no response to the treatment. Six patients occurred IFI-related mortality including 3 cases in active state and 3 in stable state. At the end of follow-up, 26 patients were alive, 20 patients die of leukemia relapse and 17 died of transplant-related mortality. Five-year overall survival (OS) and disease-free survival (DFS) were 38.0% and 34.0%, respectively. OS and DFS were similar between active patients and stable patients. ConclusionsThe results suggest that active fungal infection is not a contraindication for allo-HSCT. It appears to be safe and effective to choose the antifungal agent for second prophylaxis based on treatment response of initial antifungal therapy. Disclosures:No relevant conflicts of interest to declare.

Prevention and treatment of febrile neutropenia

Febrile Neutropenia is a relevant factor for mortality after chemotherapy. Dependent upon factors like duration of neutropenia (≥7 d means high-risk situation), patient- and disease specific criteria e.g. defined in the MASCC score (Multinational Association of Supportive Care in Cancer) the individual risk for the patient for the need of being hospitalized can be estimated. Antimicrobial therapy has to be started immediately, to avoid high mortality. Empiric or calculated antiinfective therapy includes broadspectrum-lactam antibiotics in first-line. After 72 to 96 h of treatment, when the patients are still febrile and clinically not improving, an empiric switch of the antibiotic treatment can be considered, e.g. closing the gaps in the gram-positive spectrum. In this situation high risk patients also should receive an antifungal agent with activity against aspergillus spp. Strategies to prevent infection in neutropenia are antiinfective prophylaxis or the use of G-CSF (granulocyte-colony stimulating factor). Antibiotic prophylaxis might help to prevent infections and to improve outcome esp. for high risk patients. Antifungal prophylaxis including Aspergillus species is recommended in the situation of induction therapy for acute myelogenic leukemia. Patients, expecting a phase of prolonged neutropenia with a history of mold infection should receive a secondary antifungal prophylaxis.

Antifungal Chemoprophylaxis in Children and Adolescents with Haematological Malignancies and Following Allogeneic Haematopoietic Stem Cell Transplantation

Invasive opportunistic fungal infections are important causes of morbidity and mortality in children and adolescents with cancer or haematopoietic stem cell transplantation (HSCT). Difficulties in establishing the diagnosis continue to delay antifungal therapy, and this has been shown to adversely impact on survival. Apart from ongoing attempts to improve early recognition, effective chemoprophylaxis of invasive fungal infections remains a goal of high priority in populations with disease-related incidence rates of 10% or higher. These include patients with acute myeloid leukaemia, high-risk acute lymphoblastic leukaemias, recurrent leukaemias and those following allogeneic HSCT. Incidence rates in other paediatric cancer entities, including autologous HSCT, are considerably lower and do not justify the general implementation of antifungal prophylaxis. The difficulties in obtaining a timely diagnosis, the consequences of infectious morbidity on delaying anticancer treatment, and mortality rates >20% and >50% for invasive yeast and mould infections, respectively, provide a clear rationale for antifungal prophylaxis in high-risk populations. However, while antifungal prophylaxis has become part of infectious disease supportive care algorithms in most paediatric leukaemia and allogeneic transplantation programmes, antifungal prophylaxis remains a topic of controversy, with no clear consensus amongst different centres and groups. This is largely based on the limited paediatric data, with only a small number of meaningful studies, and on the fact that the scientific evidence for the benefit of antifungal prophylaxis has been generated exclusively by prospective, randomized, clinical phase III trials conducted in adults with comparable, but not similar conditions. In this article, we briefly review the epidemiology of invasive fungal infections in children and adolescents with cancer and following HSCT; delineate regulatory principles of paediatric drug development with relevant examples for their successful implementation with new antifungal compounds; provide information on the pharmacology and paediatric development of current antifungal compounds; discuss for each compound the evidence for effectiveness as primary or secondary antifungal prophylaxis in adults and the pertinent data published in paediatric patients; and conclude by providing practical options for prophylaxis in children and adolescents with haematological malignancies and following allogeneic HSCT.

Impact of previous invasive pulmonary aspergillosis on the outcome of allogeneic hematopoietic stem cell transplantation

BackgroundInvasive pulmonary aspergillosis (IPA) is one of the major complications encountered by patients receiving chemotherapy for hematologic malignancies. The prolonged period of intense immunosuppression following allogeneic hematopoietic stem cell transplantation (HSCT) may increase the risk of IPA recurrence in patients with a history of IPA. We evaluated the impact of a history of IPA on allogeneic HSCT outcome, and examined the incidence of IPA after HSCT.MethodsThis retrospective study included 22 patients with a history of IPA prior to receiving allogeneic HSCT at the Samsung Medical Center from 1995 to 2007. Diagnosis of IPA was defined as proven (N=5), probable (N=0), or possible (N=17).ResultsAll 22 patients received amphotericin-based regimens to treat pre-transplant IPA. Secondary antifungal prophylaxis was administered to 10 patients during HSCT. The development of post-transplant IPA was observed in 2 patients. One of the patients died from septic shock within 2 days of the diagnosis of possible IPA. The other patient recovered from IPA, but eventually had a relapse of the primary disease. Of the 22 patients, the overall 2-year survival rate was 63% (95% confidence interval [CI]: 41-85), and the transplant-related mortality rate was 19% (95% CI: 0-38).ConclusionOur results suggest that a history of IPA prior to HSCT does not have an adverse impact on transplant outcomes, although the small number of cases was a limitation in this study. Future studies involving a larger number of cases are needed to further examine this issue.

Secondary Antifungal Prophylaxis in Hematopoietic Stem Cell Transplantation (HSCT)/Acute Leukemia Patients

In this review, the role of secondary antifungal prophylaxis (SAP) in prevention of invasive fungal infections (IFIs) in patients with leukemia and in those receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) is discussed. A history of IFI is not an absolute contraindication for allo-HSCT or continuation of cytotoxic chemotherapy, provided that SAP is administered. We suggest that the last antifungal drug successfully used for treatment of the previous IFI is also used for SAP; during SAP, we propose an algorithm of thorough clinical, radiological and microbiological monitoring with monthly CT scan and twice weekly galactomannan assays. However, the optimal preventive strategy for patients with a prior IFI has not been defined and concerted efforts are warranted to optimize the management of affected patients.

Voriconazole is Effective as Secondary Antifungal Prophylaxis in Leukemia Patients with Prior Pulmonary Fungal Disease: Case Series and Review of Literature

Although previous invasive fungal diseases (IFD) pose a significant risk of reactivation during successive chemotherapies in patients with acute leukemia, and secondary antifungal prophylaxis is regarded as mandatory, much remains unknown about the optimal strategy including the efficacy of voriconazole. During January 2006 and October 2008, a total of 15 patients with acute leukemia had pulmonary IFD (4 probable and 11 possible cases) before or during chemotherapy. After successful treatment of primary IFD with oral voriconazole, all of them received voriconazole during a total of 35 courses of successive chemotherapy. All but one patient successfully accomplished planned treatment without suspected IFD or significant toxicity despite profound neutropenia. We retrieved the previous reports of myelosuppressive therapies after IFD using various secondary prophylaxes, and showed that voriconazole is the most effective drug to suppress IFD relapses.

Voriconazole as secondary antifungal prophylaxis in stem cell transplant recipients (reply)

I do agree with Cordonnier and colleagues who in this issue of the Journal underline the importance of a proper definition of secondary antifungal prophylaxis (SAP) in patients with a previous invasive fungal disease (IFD). [1][1] The term secondary prophylaxis is only applicable to a population

Voriconazole as secondary antifungal prophylaxis in stem cell transplant recipients

A recently published editorial by Dr. Girmenia addressed the difficult issue of preventing invasive fungal disease in hematology patients. [1][1] The author concluded that several questions remained unanswered concerning the use of secondary antifungal prophylaxis in this setting. We agree with Dr.