Post-Transplant Pulmonary Function Abnormalities Normalize in Survivors by the Second Decade After Allogeneic Stem Cell Transplantation

Abstract 1967

Following allogeneic stem cell transplant (SCT), late-onset severe pulmonary complications occur in more than 10% of patients and confer an increased risk of mortality in the first few years post transplant. Whether pulmonary repair can occur subsequently is not well characterized. We prospectively collected pulmonary data on 138 (60 female, 78 male) recipients of allogeneic SCT from HLA identical siblings surviving > 5 years. The median age at transplant was 36 years. Indications for transplant were CML (63), AML (31), MDS (19), ALL (12) and others (14). 126 patients received ≥1200 cGy TBI-based conditioning with or without lung shielding, 3 received 400 cGy TBI-based conditioning and 9 patients received no irradiation. The graft was ex vivo T cell depleted in 131 recipients except six who received non-myeloablative SCT. Of the survivors, 26 had no cGvHD, 70 had cGvHD lasting less than 3 years and 42 had prolonged cGvHD requiring systemic immunosuppression for more than 3 years. Of the 17 patients who died beyond 5 years, 4 died of pulmonary causes, including two with lung cancer. Pre-transplant abnormalities (< 80% predicted) in PFTs were found in 15.9% of subjects in the following declining frequency: FVC%, VC, TLC, FEV1, DLCO_Adj (adjusted for hemoglobin and alveolar ventilation) Hb/VA and FEV1/FVC. Baseline (BL) PFTs served as the reference for all subsequent measurements at 5, 10 and 15 years for each survivor. The only parameter showing a clinically significant decline post transplant was DLCO_Adj at the 5-year mark, with subsequent normalization [paired t-test]. The median DLCO_Adj at 5, 10 and 15 years were 88%(p<0.001), 98%(p=NS) and 100%(p=NS) of BL, respectively. Multivariable modeling (forward-stepwise multiple regression) identified the presence of chronic GVHD (p=0.017) and abnormal BL DLCO_Adj (P=0.023) as the only factors associated with the decline in DLCO_Adj at 5 years but excluded smoking, conditioning intensity, TBI dose to the lungs and demographic variables. In conclusion, poor pulmonary function as measured by DLCO_Adj within 5 years of SCT can normalize by 10 years. Chronic GVHD and pretransplant DLCO_Adj are important contributory factors.

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