Air Leak Syndrome (ALS) Following Allogeneic Stem Cell Transplantation (SCT): A Report of 22 Patients from Kanto Study Group for Cell Therapy (KSGCT) in Japan.
Authors: Sakai Rika , Kanamori Heiwa , Okamoto Shinichiro , Yoshiba Fumiaki , Fujimaki Katsumichi , Sakura Tohru , Fujisawa Shin , Kawai Nobutaka , Nakaseko Chiaki , Onoda Masahiro , Matsushima Takafumi , Maruta Atsuo , Sakamaki Hisashi 
Published: October 2019

Abstract
Background: Air leak syndrome (ALS) such as pneumothorax is a relatively rare pulmonary complications following SCT. We investigated patients who developed ALS after SCT to clarify a clinical significance or its impact on transplant outcome.
Patients and Methods: We retrospectively surveyed 1672 patients who received SCT between January 1993 and July 2006 at 10 hospitals participating in the KSGCT. The medical records of those patients were reviewed at each institution. ALS including pneumothorax (PT), mediastinal emphysema (ME) or subcutaneous emphysema (SE) was diagnosed by findings of chest X-ray and/or computed tomography images.
Results: Twenty-two patients (1.3%) were diagnosed as having SCT-associated ALS. Underlying diseases included 11 AML, 6 ALL, 2 CML, 2 ML and 1 SAA. The median age of recipients with ALS was younger than those without ALS (25 years: range, 12–53 versus 38 years: range, 8–62, p=0.002), and there was a male predominance in recipients with ALS (M/F ratio; 10:1 versus 1.6:1 p=0.0002) .The median onset of ALS was day +574 (range, day +105 to +4847) after SCT. The types of ALS were as follows; PT in 8 patients: ME/SE in 7, and PT+ME/SE in 7. Thirteen patients received bone marrow (8) or peripheral blood (5) from related donors and 9 received bone marrow from unrelated donors. Myeloablative conditioning was carried out on all but one patients. Total body irradiation or total lymphnode irradiation was used for 19 patients. Graft-versus-host disease (GVHD) prophylaxis was attempted with cyclosporine in 11 patients or tacrolimus in 11 patients. Acute GVHD (grade II–IV) occurred in 13 (59%) patients and extensive chronic GVHD in 19 (86%). The history of steroid therapy was confirmed in 21 (95%) patients and 17 (77%) were still on immunosuppressive therapy with steroids at the diagnosis of ALS. Before developing ALS sixteen patients (73%) had experienced non-infectious pulmonary complications (NIPC) including interstitial pneumonia (IP) (5 patients), bronchiolitis obliterans (BO) (5), bronchiolitis obliterans organizing pneumonia (BOOP) (3), IP+BOOP (2), and radiation pneumonitis, and the median time from the diagnosis of NIPC to the onset of ALS was 56 days (range, 3–4421 days). The treatment of ALS included drainage in 13, increase of immunosuppressant in 3, and observation in 6. Improvement was obtained in 14 patients, deterioration in 4, and the rest had no change. Thirteen patients died and respiratory complications were the direct causes of death in 9. Overall survival at 2 years from the onset of ALS in patients with PT, PM/SE and PT complicated with ME/SE was 62.5%, 57.1% and 0%, respectively (P=0.0125).
Conclusions: Although SCT-associated ALS is a rare complication, it is not infrequent in patients who developed NIPC requiring steroids therapy after SCT. The unfavorable outcome in patients presenting PT and PM/SE requires better understanding its pathogenesis and innovative therapies.