Clinical Issues Regarding Relapsing Aspergillosis and the Efficacy of Secondary Antifungal Prophylaxis in Patients with Hematological Malignancies

Abstract

Advancements in early diagnosis and the introduction of effective agents have improved the rates of response of aspergillosis to primary antifungal therapy. These changes allow the subsequent continuation of cytotoxic chemotherapy and/or performance of hematopoietic stem cell transplantation in an increasing number of patients with hematological malignancies. These developments have increased interest in secondary prophylaxis of aspergillosis, because the resumption of myelotoxic chemotherapy in these patients is associated with high rates of relapse of this opportunistic mycosis in the absence of prophylaxis. However, the risk factors for relapsing invasive aspergillosis and the strategies for reducing risk are not well defined. Furthermore, differentiating aspergillosis relapse from reinfection with a new Aspergillus isolate is problematic when using the available laboratory tools. We summarize the existing knowledge regarding the pathogenesis of, risk factors for, and natural history of relapsing invasive aspergillosis and review the limited data regarding the role of secondary antifungal prophylaxis.

Surgical resection of persistent pulmonary fungus nodules and secondary prophylaxis are effective in preventing fungal relapse in patients receiving chemotherapy or bone marrow transplantation for leukemia

“…3 In allogeneic bone marrow transplant recipients, particularly, mortality rates owing to aspergillosis are very high, approaching 90%; 2,4 for this reason, secondary prophylaxis with antifungal drugs is usual. 5 In particular, in patients scheduled for bone marrow transplantation, surgical procedures should be considered when there is persistence of only one pulmonary nodule or when there is cavitation. Such lesions can persist and be colonized by other bacteria or by the same mycotic agent, despite prolonged antifungal treatment.…”

Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection

“…4 However, there is a general consensus for giving antifungals to patients undergoing a new neutropenic phase or a transplant, supported by better prognosis in patients who have received any secondary prophylaxis, than in patients who have not. 5 The successful use of Caspofungin given to prevent relapse of fungal infection in transplanted patients was reported in 26 patients with a history of probable or proven infection, although in 15% treatment had to be changed to voriconazole, amphotericin B or Ambisome because of clinically manifest fungal infection under Caspofungin prophylaxis.…”

“…1,2 The recent development of more effective, less toxic antifungal drugs and routine early implementation of high-resolution chest computer tomography (CT), leading to prompt intensive antifungal therapy, have improved responses and survival, allowing an increase of antifungal treatments, including secondary antifungal prophylaxis. 3,4 The possibility of reactivation of a previous episode of fungal infection during a following neutropenic phase or in patients undergoing stem cell transplantation is extremely high and is associated with a very poor prognosis. 5 In the particular case of stem cell transplantation, delay of treatment because of previous IFI, mainly due to different classes of Aspergillus, may also contribute to leukemia relapse in patients with high-risk disease.…”

Assessing the risk of transplant-related complications and individually tailoring the HSCT procedure in children and adolescents—is it possible?

“…Unrelated donor HSCT, duration of primary antifungal therapy of less than 1 month, partial clinical response to an earlier invasive aspergillosis and incomplete resolution of imaging findings, 44 predispose to a relapse of invasive aspergillosis after HSCT. Surgical resection followed by administration of antifungal therapy might decrease the probability of relapse after HSCT in cases of residual aspergillosis lesion.…”

“…Surgical resection followed by administration of antifungal therapy might decrease the probability of relapse after HSCT in cases of residual aspergillosis lesion. 44,45 Risk factors for thyroid toxicity Radio therapy involving the head, neck, and spine, and in particular high doses of radiation at a younger age (especially females) are risk factors related to thyroid problems. 32 Compensated hypothyroidism is the most frequent thyroid complication following TBI, with a frequency of 15 vs 2.1% of overt hypothyroidism.…”