Incidence and outcomes of invasive fungal disease in adult patients with acute lymphoblastic leukemia treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone: implications for prophylaxis

Henden, Andrea S.; Morris, Kirk; Truloff, Natasha; Nakagaki, Midori; Kennedy, Glen

doi:10.3109/10428194.2012.740561

Cited by 22 publications

(13 citation statements)

References 12 publications

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“…This occurred despite 52.9% of patients receiving mold-active prophylaxis. This finding is consistent with a 28% incidence reported at another Australian center 8 and may be attributed to the increasing intensity of induction chemotherapy protocols for lymphoblastic haematologica 2015; 100:e465 …”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nsupporting

confidence: 90%

“…Use of antifungal prophylaxis in this cohort is challenging given the potential for drug interactions with vinca alkaloids. 8 Triazole antifungal drugs potentiate vincristine-related neuropathy and although antifungal prophylaxis is sometimes administered intermittently or withheld during vincristine-containing treatment, this approach is complicated by the variable half-lives of these agents.…”

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confidence: 99%

“…Overall, we observed a 30-day all-cause mortality of 31.0% and this is consistent with previous studies. 8 There is a possibility that IFD diagnoses are delayed in these patients as they lie outside traditional risk groups due to uncertainty surrounding IFD risk, the paucity of data on IFD epidemiology and absence of standardized antifungal prophylaxis recommendations amid evolving disease treatments.…”

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confidence: 99%

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Epidemiology of invasive fungal disease in lymphoproliferative disorders

et al. 2015

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ous oral chemotherapy in myeloma cohort, IFD rate per 10,000 treatment days not provided. © F e r r a t a S t o r t i F o u n d a t i o nhaematologica 2015; 100:e463 Table 2. Characteristics of patients with lymphoproliferative disorders with invasive fungal disease (2009)(2010)(2011) LETTERS TO THE EDITOR © F e r r a t a S t o r t i F o u n d a t i o nFluconazole and mold-active antifungal prophylaxis were administered to 287/773 (37.1%) and 38/773 (4.9%) patients, respectively. Patients with precursor lymphoid neoplasms had the highest prevalence of IFD (5/17; 29.4%, 95% CI 9.5-68.6%), followed by patients with mature B-cell neoplasms-CLL/SLL (4/51; 7.8%, 95% CI 2.1-20.1%), DLBCL (8/186; 4.3%, 95% CI 1.9-8.5%) and plasma cell neoplasms (7/251; 2.8%, 95% CI 1.1-5.7%). IFD events per treatment days demonstrated a similarly larger relative burden of disease in patients with precursor lymphoid neoplasms (10.7 IFD per 10,000 treatment days) ( Table 1). Mold-active antifungal prophylaxis was used in 52.9% of patients with precursor lymphoid neoplasms. Of the five patients with precursor lymphoid neoplasms who developed IFD, three had received fluconazole prophylaxis, one had received posaconazole prophylaxis and one received no antifungal prophylaxis. IFD was observed to occur at different treatment stages of disease, and these are summarized in Table 2.Aspergillus species was the most frequently identified fungal pathogen (13 cases) (cultured in 7 cases; detected on PCR in 8 cases). Other fungal pathogens, in order of reducing frequency included Candida (5 cases), Scedosporium (1 case), Scopulariopsis (1 case) and Cryptococcus (1 case) species. The pulmonary system (19 cases) was the most common site of IFD, followed by blood (5 cases), sinus (2 cases), soft tissue/viscera (2 cases) and central nervous system (1 case). Of the 29 patients treated for IFD, 12 (41.4%) required admission to the intensive care unit and 30-day all-cause mortality was 31.0% (9/29).IFD is an important and potentially modifiable cause of morbidity and mortality in patients with lymphoproliferative disorders receiving chemotherapy. Few studies have described the epidemiology and treatment outcome of IFD in these patients and none has incorporated all of the current diagnostic strategies available (e.g. Aspergillus PCR, galactomannan and FDG PET/CT diagnostics). Our study identified an overall IFD prevalence of 3.8% with cases occurring in all disease subsets except mature Tand NK-cell lymphoma. The prevalence of IFD was highest in patients with precursor lymphoid neoplasms (29.4%). This occurred despite 52.9% of patients receiving mold-active prophylaxis. This finding is consistent with a 28% incidence reported at another Australian center 8 and may be attributed to the increasing intensity of induction chemotherapy protocols for lymphoblastic haematologica 2015; 100:e465 R: rituximab; CVP:cyclophosphamide/vincristine/prednisolone; bortez: bortezomib; dex: dexamethasone; thal: thalidomide; len: lenalidomide; bleomycin, vincristine, etopo...

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nsupporting

confidence: 90%

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confidence: 99%

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Epidemiology of invasive fungal disease in lymphoproliferative disorders

et al. 2015

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“…Of note, acute lymphoblastic leukemia (ALL) was the third most common condition after acute myeloid leukaemia (AML) and allogeneic HSCT, respectively [51], highlighting the growing recognition that ALL is a predisposing factor for IFD as others have also noted [52,53].…”

Section: Clinical Efficacy For Invasive Fungal Infectionsmentioning

confidence: 99%

Isavuconazole: A new Extended Spectrum Triazole for Invasive Mold Diseases

Ananda‐Rajah

Kontoyiannis

2015

Future Microbiol.

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Isavuconazole is the first broad spectrum prodrug triazole with efficacy against invasive fungal diseases including aspergillosis and mucormycosis. Characteristics include linear dose-proportional pharmacokinetics, intravenous and oral formulations allowing therapeutic streamlining, once daily dosing, absence of nephrotoxic solubilizing agents and excellent oral bioavailability independent of prandial status and gastric acidity. An open label noncomparator study demonstrated encouraging results for isavuconazole as primary or salvage therapy for a range of fungi including mucormycosis. Isavuconazole had fewer premature drug discontinuations and adverse events in the eye, hepatobiliary and psychiatry systems than the comparator agent, voriconazole in a randomized double-blind clinical trial. Cross-resistance of isavuconazole best correlates with voriconazole. In vitro resistance is not invariably predictive of clinical failure. Isavuconazole signals progress in pharmacokinetics, bioavailability and toxicity/tolerability supported by clinical efficacy from Phase III trials.

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“…15 Subsequent to the 2008 guidelines, two Australian studies identified patients with ALL to be at high risk of IFD, including mould infections. 16,17 Hence, it is not surprising to find that the majority of clinicians surveyed use mould-active prophylaxis during ALL treatment and that liposomal amphotericin B was the preferred agent in most cases (53%) with fluconazole an alternative. This variation in practice is reflective of the uncertainties that surround the duration of IFD risk and need for prophylaxis.…”

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confidence: 99%

Survey of antifungal prophylaxis and fungal diagnostic tests employed in malignant haematology and haemopoietic stem cell transplantation (HSCT) inAustralia andNewZealand

Hal

Gilroy

Morrissey

et al. 2014

Internal Medicine Journal

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This article reports the findings of a survey developed to assess the current use of antifungal prophylaxis among haematology and infectious disease clinicians across Australia and New Zealand, and their alignment with existing consensus guidelines for the use of antifungal agents in the haematology/oncology setting (published 2008). Surveyed clinicians largely followed the current recommendations for prophylaxis in the setting of induction chemotherapy for acute myeloid leukaemia, as well as autologous and low-risk allogeneic haemopoietic stem cell transplantation (HSCT). In keeping with guideline recommendations, posaconazole was the agent used by most centres for high-risk allogeneic HSCT. However, its routine continuation for 75-100 days posttransplantation without de-escalation suggested use beyond those indications described in the 2008 guidelines, namely pre-engraftment neutropenia and graft-versus-host disease. Variations in practice were observed in other settings, such as acute lymphoblastic leukaemia and myelodysplastic syndrome, reflecting the general lack of evidence for antifungal prophylaxis in these patient populations and changing perceptions of risk. With regard to the availability of testing in cases of suspected breakthrough IFD, 40% of centres did not have access to investigative bronchoscopy within 48 h of referral, and results of Aspergillus galactomannan (GM), fungal polymerase chain reaction and therapeutic drug monitoring (TDM) were not available within 48 h in 83%, 90% and 85% of centres respectively. The survey's findings will influence the recommendations provided in the updated 2014 consensus guidelines for the use of antifungal agents in the haematology/oncology setting.

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Incidence and outcomes of invasive fungal disease in adult patients with acute lymphoblastic leukemia treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone: implications for prophylaxis

Cited by 22 publications

References 12 publications

Epidemiology of invasive fungal disease in lymphoproliferative disorders

Epidemiology of invasive fungal disease in lymphoproliferative disorders

Isavuconazole: A new Extended Spectrum Triazole for Invasive Mold Diseases

Survey of antifungal prophylaxis and fungal diagnostic tests employed in malignant haematology and haemopoietic stem cell transplantation (HSCT) inAustralia andNewZealand

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