Prognostic Effect of Decline in Pulmonary Function Testing after Autologous Stem Cell Transplantation

Background

Large retrospective analyses of patients (pts) undergoing allogeneic stem cell transplant have demonstrated association between decline in pulmonary function and increases in mortality. There is a paucity of similar evidence for pts undergoing autologous stem cell transplant (ASCT). We conducted a retrospective study of lymphoma pts undergoing ASCT to investigate association between early post-transplant decrease in pulmonary function tests (PFTs) and mortality. We hypothesized that decreases in pulmonary function in the early post-transplant period in ASCT pts would be associated with greater risk of overall and non-relapse mortality.

Methods and Patients

We identified 853 lymphoma pts age ≥18 years who underwent ASCT at Cleveland Clinic between 2000-2016 and had completed both pre- and post-ASCT PFTs. Two PFT values were assessed: percent predicted FEV1 and DLCO. Endpoints for the study included overall survival (OS) and non-relapse mortality (NRM). Decrease from pre- to post-ASCT for each was defined as ≤5%, 5.01-10%, or >10%. Variables associated with decrease in PFTs were identified with Cochran-Mantel-Haenszel trend tests. Risk factors were identified with Cox analysis (OS) or Fine and Gray regression (NRM); results are presented as hazard ratio (HR) and 95% confidence interval (CI).

Results

The study cohort was predominantly male (63%) and Caucasian (92%) with a median age of 54 years (range 19-78). Primary diagnosis included Hodgkin lymphoma (19%) and non-Hodgkin lymphoma: B cell low-grade (16%) and high-grade (57%), and T cell (8%). The majority had advanced stage disease (79%), received <3 prior chemotherapy regimens (74%), no prior radiation (77%) and were never smokers (56%). Prior bleomycin (23%) and brentuximab (2%) exposure was low. Busulfan, etoposide and cyclophosphamide was the preparative regimen in 98% of pts. Median time to neutrophil and platelet engraftment were 10 and 15 days respectively. At a median follow up of 64 months (range 3-208) 62% of our cohort was alive and 43% had relapsed. Pre-ASCT PFTs were performed at a median of 51 days (range 9-205) prior to transplant. Median pre-transplant FEV1 and DLCO were 93% and 75% of predicted respectively when corrected for anemia. Post-transplant PFTs were obtained at a median 43 days post-transplant (25-92). Decreases in FEV1 of ≤5%, 5.01-10%, and >10% were observed in 71%, 15%, and 15% of pts, respectively. Corresponding decreases in DLCO were 70%, 11%, and 20%, respectively. Decrease in FEV1 was associated with male gender, intermediate risk disease, chemo-mobilization, and increased days of apheresis. Decreasing DLCO was associated with Caucasian ethnicity, and advanced stage. Pts with FEV1 decline were more likely to experience increased hospital stay and readmission within 100 days post ASCT. Prior bleomycin use did not impact PFTs or outcomes.

For our cohort, 5- and 10-year NRM were 10% and 15% respectively; 5- and 10-year OS were 63% and 53% . In univariate analysis, pts with >10% FEV1 decrease had significantly worse NRM (HR 2.07, 95% CI 1.27-3.38, p=0.004) (Figure 1) and OS (HR: 1.42, 95% CI 1.07-1.89, p=0.016) (Figure 1a) than those with ≤5% decrease; pts with 5.01-10% FEV1 decrease had similar NRM (HR 1.58, 95% CI 0.92-2.72, p=0.10) and OS (HR 1.15, CI 0.85-1.57, p=0.37) to those with ≤5% decrease . Only minimal decreases in DLCO (0.01-5%) impacted NRM (HR: 0.23, CI = 0.06 - 0.95, p=0.042), while >5% decline had no significance on NRM or OS. In multivariable analysis, >10% FEV1 decrease retained significance for NRM (HR 1.96, 95% CI 1.20-3.20, p=0.008), with a trend towards poor OS (HR 1.33, CI 0.99-1.77, p=0.06) (Figure 2). Pts with 5.01-10% decrease had marginally higher risk of NRM (HR 1.55, 95% CI 0.90-2.66, p=0.11) but not OS (HR 1.14, 95% CI 0.83-1.55, p=0.42). Other prognostic factors for increased NRM included older age, chemo-mobilization, and more days of apheresis. These three were also prognostic for worse OS along with more prior chemotherapy and high-risk disease.

Conclusion

Decrements of FEV1 >10% in the early post-transplant period are associated with increased NRM and inferior OS in lymphoma pts undergoing ASCT. Greater decrease in DLCO was not associated with decreased OS or increased NRM. Further stratification and analysis of the population with large decreases in pulmonary function may help with development of screening and interventional strategies in high risk pts.

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