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.