Pulmonary Function Abnormalities 5 Years or More Following Myeloablative and Non-Myeloablative Allogeneic Stem Cell Transplantation for Hematological Disorders - Impact of Chronic GVHD.

Pulmonary function was studied in sixty nine consecutive patients with hematological diseases (65 malignant; 4 benign) 5–12 (median 7.5) years following allogeneic stem cell transplantation from HLA-matched siblings. Fifty-six (81%) patients received total body irradiation-(TBI) based myeloablative bone marrow or peripheral blood stem cell transplantation (MST) for hematological malignancies and 13 (19%) received a fludarabine/cyclophosphamide non-myeloablative peripheral blood stem cell transplantation (NST) for malignant (9) or benign (4) hematological disease. Median age of cohort was 37 years (MST 37, range 10–55; NST 34, range 15–68 years). Thirty nine patients were male. Eleven were smokers. Baseline pulmonary function tests (PFT) showed a median DLCO of 90% predicted (range 59–156%) and FEV1 of 97% predicted (range 64 to132%). Significant pre-transplantation PFT abnormality occurred in 19 (27.5%) patients (DLCO and/or FEV1 <80% of predicted). Twenty five (36%) patients developed acute graft versus host disease (aGVHD) and 43(62%) developed chronic GVHD (cGVHD). At long-term follow-up at a median of 7.5 years after transplant, 32 (42%) patients had PFT abnormalities, 26 with a predominantly restrictive pattern and 6 with a predominantly obstructive pattern. Twenty-two (32%) patients had a mild to moderate decline in PFT (compared with pre-transplant values DLCO/FEV1 value). Of the 32 patients with PFT abnormalities none required supplemental oxygen and only 12 (17.4%) were symptomatic, which included 10 (14.5%) with the most severely depressed pulmonary function (all with predominantly restrictive lung function). In univariate analysis, development of cGVHD (p <0.0001); pre-transplant PFT abnormality (p<0.0001) and a history of smoking (p=0.03); was associated with increased incidence of late PFT abnormality. In multivariate regression analysis, cGVHD (relative risk 36.1; 95% CI 4.1–320) and pre-transplant DLCO/FEV1 of less than 80% of predicted (relative risk 5.5; 95% CI 1.07–29) were independently associated with late decline in PFT. When analyzed for symptomatic PFT abnormality beyond 5 year post-transplant similar results were obtained. The incidence of late PFT abnormality was comparable in both MST (24/56) and NST (5/13) (p=0.51). Our result indicates that a significant proportion of patients developed late PFT abnormality after transplantation, however only a minority are symptomatic. In this series of patients receiving conditioning regimens of different intensity, cGVHD was the only transplant-related risk factor predictive for late pulmonary function defects.