Leukemia & Lymphoma, February 2011; 52(2): 339–340
LETTER TO THE EDITOR
An early computed tomography-guided antifungal treatment strategy is safe and efficacious in patients undergoing chemotherapy for high-risk acute leukemia
KABIR MOHAMMED1, FIONA DIGNAN1, MARK E. ETHELL1, FAITH E. DAVIES1, GARETH J. MORGAN1, UNELL RILEY2, STEVE EVANS3, MICHAEL N. POTTER1, & BRONWEN E. SHAW1 1
Section of Haemato-oncology, 2Microbiology Department, and 3Pharmacy, Royal Marsden NHS Foundation Trust, Surrey, UK (Received 26 August 2010; accepted 21 September 2010)
We read with interest the recent review by Ruping et al. [1] on the prevention and treatment of invasive fungal infections (IFIs) in patients with leukemia. The Royal Marsden NHS Foundation Trust is a large cancer center in south London, treating patients with high-risk acute leukemia (AL) with intensive chemotherapy and allogeneic transplant. In January 2006, we instituted an early treatment strategy for IFIs based on computed tomography (CT) criteria rather than empirical therapy. Patients underwent high-resolution CT (HRCT) of the thorax (1.25 mm sections at intervals of 10 mm) after 72 h of persistent antibiotic-resistant neutropenic fever. Patients with a positive HRCT (based on major changes: cavitation, air-crescent sign, and halo sign; or minor changes: nodules and new infiltrates) commenced liposomal amphotericin B (3 mg/kg once daily). Patients with a negative CT scan continued itraconazole prophylaxis. We had previously found this to be a feasible approach in patients undergoing allogeneic transplant [2]. Here we present results from a recent audit of 151 adult patients, treated between 2006 and 2009, with intensive chemotherapy for AL in our unit. The study was approved by the clinical audit committee and patients had given informed consent. Prophylaxis with itraconazole was used in patients with acute myeloid leukemia and fluconazole in those with acute lymphoblastic leukemia. Of 151 patients identified,
62% had a persistent fever, of whom 78% had HRCT performed at 72 h. Fifty-five percent of patients had a positive scan and 45% had a negative scan. All patients with positive HRCT had antifungals commenced according to the policy. In addition, antifungal therapy was commenced in three patients with negative HRCT, and six patients with no HRCT, due to clinical symptoms and/or positive laboratory tests, and in two patients empirically during an intensive care unit admission. Thus, approximately half the patients with ongoing temperatures did not require antifungal treatment. Importantly, in this group there were no breakthrough infections or deaths due to fungal infection within 100 days. This represented a significant cost saving, and reduced toxicity to the patient from additional agents, without compromising their clinical outcome. In the group who received antifungal treatment, responses to therapy were excellent, with only two deaths directly related to IFIs (Aspergillus fumigatus, Candida dubliniensis)—both in patients with refractory leukemia. In conclusion, we believe this to be a safe and efficacious strategy for patients with AL. In line with recommendations made in a recent review by Leventakos et al. [3], we agree that an individualized patient approach within the overall strategy is critical, in particular the need to carefully correlate the HRCT findings with clinical and laboratory
Correspondence: Bronwen E. Shaw, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel: þ44-2086613794. Fax: þ44-2086429634. E-mail:
[email protected] ISSN 1042-8194 print/ISSN 1029-2403 online Ó 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2010.527407
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Letter to the Editor
parameters. It is essential for there to be rapid access to HRCT scans and excellent communication between hematological and radiology teams, with standardized reporting against agreed CT criteria. These data, and those available from our previous study, suggest that this approach may be effective, but a randomized controlled trail is warranted to further assess these results. Declaration of interest: This work was supported by an unrestricted grant from Gilead.
References 1. Ruping MJGT, Vehreschild JJ, Cornely OA. Primary antifungal prophylaxis in acute myeloblastic leukemia and myelodysplastic syndrome – still an open question? Leuk Lymphoma 2010;51: 20–26. 2. Dignan FL, Evans SO, Ethell ME, et al. An early CTdiagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality. Bone Marrow Transplant 2009;44:51–56. 3. Leventakos K, Lewis RE, Kontoyiannis DP. Fungal infections in leukemia patients: how do we prevent and treat them? Clin Infect Dis 2010;50:405–415.
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