Changing Trends in the Use of Surgical Biopsy for Diagnosis of Pulmonary Disease in Hematopoietic Cell Transplant Recipients

Introduction:  Historically, diagnosis of enigmatic pulmonary disease after hematopoietic cell transplant (HCT) has required lung biopsy.  Recent improvements in laboratory diagnostics and therapies for fungal infections have led to changes in how clinicians approach pulmonary abnormalities.  We examined temporal trends in the use of lung biopsy after HCT.  Methods:  We retrospectively reviewed patients who underwent their first allogeneic HCT at the Fred Hutchinson Cancer Research Center between the years 1993-1997 and 2003-2007.  Data on lung biopsies were abstracted from a prospectively collected database of all recipients from these two cohorts (NEJM 2010).  Outcome data were analyzed using Fisher’s exact test.  Hazards for lung biopsy for the two cohorts were determined using a Cox-proportional hazards model with death and relapse considered competing risks.  Results:  A total of 50/1418 (3.5%) patients underwent 52 post-HCT surgical lung biopsies during 1993-1997 compared with 21/1148 (1.8%) patients and 21 biopsies in the 2003-2007 cohort.  The median time to biopsy post-HCT was 72 days (IQR 32-89) for the early cohort and 97 days (IQR 33-119) for the more recent cohort, for an overall biopsy incidence of 0.052 and 0.02 per 1000 patient days, respectively.  Patients in the 2003-2007 cohort were less likely to undergo a lung biopsy (HR 0.52, CI 0.28-0.98, p=0.04) when compared to patients in the 1993-1997 cohort.  Although a similar number of patients underwent a bronchoscopy between the two cohorts (272/1418 [19.2%] vs. 243/1148 [21.1%], p=0.22), more patients in the early cohort underwent lung biopsy without antecedent bronchoscopy (26/52 [50%] vs. 18/21 [86%], p=0.007).  Infections were a more common finding at biopsy in the early cohort (35/1418 vs. 8/1148, p<0.001), but the number of biopsies demonstrating non-infectious lesions was similar between the two cohorts (17/1418 vs. 13/1148, p=0.85).  Fungal infections were the major infectious etiology in both cohorts (30/35[85%] vs. 5/8 [63%], p=0.15), but there was a significant reduction in the number of Aspergillus species found at biopsy between the cohorts (29/52 vs. 1/21, p<0.001).  A similar number of patients underwent biopsy with a therapeutic intent in the two cohorts (8/52 [15%] vs. 3/21 [14%]); all of those who underwent therapeutic biopsy in the 2003-2007 cohort had documented Mucorales species.  Conclusions:  Surgical evaluation of lung disease in HCT recipients significantly declined over a decade between 1993-1997 and 2003-2007.  This decreased incidence of lung biopsies between these two cohorts was related to a reduction in the number of biopsies for post-transplant infections, particularly for those due to aspergillosis.  We speculate that this decline is related to the introduction of galactomannan testing and the increased use of empiric therapy with extended-spectrum azoles.